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Sample records for intensive insulin therapy

  1. Intensive Insulin Therapy in Severely Burned Pediatric Patients

    PubMed Central

    Jeschke, Marc G.; Kulp, Gabriela A.; Kraft, Robert; Finnerty, Celeste C.; Mlcak, Ron; Lee, Jong O.; Herndon, David N.

    2010-01-01

    Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309). PMID:20395554

  2. Insulin therapy in the pediatric intensive care unit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units, and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic a...

  3. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children

    PubMed Central

    Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Mlcak, Ronald P.; Qian, Ting; Chinkes, David L.; Herndon, David N.

    2013-01-01

    Objective To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Design Prospective, randomized study. Setting An acute pediatric burn unit in a tertiary teaching hospital. Patients Children, 4–18 yrs old, with total body surface area burned ≥40% and who arrived within 1 wk after injury were enrolled in the study. Interventions Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose ≤215 mg/dL. Measurements and Main Results Twenty patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days post-burn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 ± 124 to 1925 ± 291 kcal/m2·day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 ± 0.8 conventional insulin therapy vs. 6.8 ± 0.9 mg/kg·min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 ± 1.3 intensive insulin therapy versus 4.8 ± 0.6 mg/kg·min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 ± 0.9 vs. 2.5 ± 0.6 mg/kg·min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 ± 0.1 to 1.7 ± 0.1 μm O2/CS/mg protein/min for state 3, p = .004; and 0.7 ± 0.1 to 1.3 ± 0.1 μm O2/CS/mg protein

  4. [Insulin therapy and parenteral nutrition in intensive care: practical aspects].

    PubMed

    Limonta, A; Gastaldi, G; Heidegger, C P; Pichard, C

    2015-03-25

    Critically ill patients are hypercatabolic due to stress and inflammation. This condition induces hyperglycemia. Muscle wasting is intense during critical illness. Its prevention is essential. This is possible by early and appropriate nutritional support. Preserving the function of the gastrointestinal tract with enteral nutrition is the gold standard. However, when targeted protein-caloric intake is not met through enteral nutrition within the first three days in the intensive care unit (ICU), supplemental parenteral nutrition is administered to reduce morbidity and mortality. In addition, in order to limit metabolic imbalance and reduce mortality, glycemic control using insulin therapy is mandatory. This article reviews the current understanding of parenteral nutrition and insulin therapy in ICU patients, and provides the decision model applied in our institution. PMID:26027204

  5. Changing practice with changing research: results of two UK national surveys of intensive insulin therapy in intensive care patients.

    PubMed

    Paddle, J J; Eve, R L; Sharpe, K A

    2011-02-01

    We conducted two telephone surveys of all United Kingdom adult intensive care units in 2007/8 and 2010 to assess practice with regard to intensive insulin therapy for glycaemic control in critically ill patients, and to assess the change in practice following publications in 2008 and 2009 that challenged the evidence for this therapy. Of 243 units that had a written policy for intensive insulin therapy in 2007/8, 232 (96%) still had a policy in 2010. One hundred and six (46%) units had updated their policy in response to new evidence, whereas 126 (54%) stated that it had remained the same. Where intensive care units had changed their policy, we found a significant increase in target limits and a wider target range. Regional variations in practice were also seen. Across seven regions, the percentage of units where the glycaemic control policy had been updated since 2007/8 varied from nil to 78.9%. PMID:21254983

  6. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

    PubMed Central

    Griesdale, Donald E.G.; de Souza, Russell J.; van Dam, Rob M.; Heyland, Daren K.; Cook, Deborah J.; Malhotra, Atul; Dhaliwal, Rupinder; Henderson, William R.; Chittock, Dean R.; Finfer, Simon; Talmor, Daniel

    2009-01-01

    Background Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. Results We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may

  7. When Intensive Insulin Therapy (MDI) Fails in Patients With Type 2 Diabetes: Switching to GLP-1 Receptor Agonist Versus Insulin Pump.

    PubMed

    Cohen, Ohad; Filetti, Sebastiano; Castañeda, Javier; Maranghi, Marianna; Glandt, Mariela

    2016-08-01

    Treatment with insulin, alone or with oral or injectable hypoglycemic agents, is becoming increasingly common in patients with type 2 diabetes. However, approximately 40% of patients fail to reach their glycemic targets with the initially prescribed regimen and require intensification of insulin therapy, which increases the risks of weight gain and hypoglycemia. Many of these patients eventually reach a state in which further increases in the insulin dosage fail to improve glycemic control while increasing the risks of weight gain and hypoglycemia. The recently completed OpT2mise clinical trial showed that continuous subcutaneous insulin infusion (CSII) is more effective in reducing glycated hemoglobin (HbA1c) than intensification of multiple daily injection (MDI) insulin therapy in patients with type 2 diabetes who do not respond to intensive insulin therapy. CSII therapy may also be useful in patients who do not reach glycemic targets despite multidrug therapy with basal-bolus insulin and other agents, including glucagon-like peptide (GLP)-1 receptor agonists; current guidelines offer no recommendations for the treatment of such patients. Importantly, insulin and GLP-1 receptor agonists have complementary effects on glycemia and, hence, can be used either sequentially or in combination in the initial management of diabetes. Patients who have not previously failed GLP-1 receptor agonist therapy may show reduction in weight and insulin dose, in addition to moderate improvement in HbA1c, when GLP-1 receptor agonist therapy is added to MDI regimens. In subjects with long-standing type 2 diabetes who do not respond to intensive insulin therapies, switching from MDI to CSII and/or the addition of GLP-1 receptor agonists to MDI have the potential to improve glycemic control without increasing the risk of adverse events. PMID:27440831

  8. Dietary Adherence and Mealtime Behaviors in Young Children with Type 1 Diabetes on Intensive Insulin Therapy

    PubMed Central

    Patton, Susana R.; Dolan, Lawrence M.; Chen, Ming; Powers, Scott W.

    2013-01-01

    Diet is an important component of diabetes treatment and integral to successful management. While intensive insulin therapy can allow patients to eat more freely, it is not known how the rapid uptake of intensive therapy in young children with type 1 diabetes has impacted their diet and if diet and healthful eating in young children correlates with mealtime behaviors and glycemic control. This study examined diet, mealtime behaviors, and glucose control in a sample of 39 young children on intensive therapy. This was a one-sample, cross-sectional study. Children had a mean age of 5.1±1.1 years. Children’s 3-day diet diaries were assessed using a deviation scale (measure of adherence) and a healthy eating index. Mealtime behaviors were assessed using the Behavioral Pediatric Feeding Assessment Scale. Children’s glucose control was measured using continuous glucose monitoring. Children’s mean carbohydrate intake was 72%±24% of the recommended levels based on their age, sex, size, and activity level, and children exceeded national guidelines for percentage of calories from fat and saturated fat. A more healthful diet correlated with fewer child mealtime behavior problems, but better dietary adherence correlated with more parent mealtime behavior problems. Even in the context of intensive management, diet can be problematic for young children with type 1 diabetes. Parent-reported problems with mealtime behaviors seem to correlate with healthy eating and dietary adherence. PMID:23351629

  9. Clinical Impact of Sample Interference on Intensive Insulin Therapy in Severely Burned Patients: A Pilot Study

    PubMed Central

    Tran, Nam K.; Godwin, Zachary R.; Bockhold, Jennifer C.; Passerini, Anthony G.; Cheng, Julian; Ingemason, Morgan

    2013-01-01

    Objective Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). We evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. Methods The performance of two point-of-care glucose monitoring systems (GMS): (a) GMS1, an autocorrecting device, and (b) GMS2, a non-correcting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs. GMS2 accuracy paired against a plasma glucose reference. Next we enrolled 12 patients in a pilot randomized controlled trial (RCT). Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111–151 mg/dL and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. Results In the prospective study, GMS1 results were similar to plasma glucose results (mean bias: −0.75[4.0] mg/dL, n=60, P=0.214). GMS2 results significantly differed from paired plasma glucose results (mean bias: −5.66[18.7] mg/dL, n=60, P=0.048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2[27.2], P<0.001). RCT results reported lower mean bias (P<0.001), glycemic variability (P<0.05), mean insulin rate (P<0.001), and frequency of hypoglycemia (P<0.001) in the GMS1 group than the GMS2 group. Conclusions Anemia and high dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT. PMID:23884048

  10. [Is intensive functional insulin therapy the method of choice in newly diagnosed type-1 diabetes mellitus?].

    PubMed

    Araszkiewicz, Aleksandra; Zozulińska, Dorota; Trepińska, Magdalena; Wierusz-Wysocka, Bogna

    2004-11-01

    The aim of our study was a prospective evaluation of type 1 diabetic patients treated with intensive insulin therapy. We recruited 100 patients (62 males and 38 females) aged 24.3+/-6.2 years with newly diagnosed type 1 diabetes. The mean observation period was 5.2+/-1.5 years. Parameters of diabetes metabolic balance, occurrence of chronic complications and patients' knowledge about the disease and the methods of its treatment were evaluated. 68% of the patients controlled their glycaemia regularly before main meals and 53% of them had a diabetic diary. In the knowledge test 20% of the subjects reached < or = 11 points, 62% 11-17 points and 18% > 17 points (mean 14.4+/-3.2 points of maximal 20 to achieve). The mean result in the questionnaire of knowledge about the disease was 28.1+/-4.9 points. Fasting glycaemia was 7.2+/-3.4 mmol/l, 2h postprandial glycaemia 9.4+/-3.6 mmol/l, HbA1c 7.5+/-1.4%, the mean C-peptide level 0.9+/-0.4 ng/ml and the number of hypoglycaemic episodes was 6/individual/month. We observed a statistically significant correlation between the level of patients' knowledge and HbA1c (r=-0.31, p<0.05). Retinopathy and nephropathy were detected in 8 (9%) and 6 (6.8%) subjects respectively. The risk of microangiopathy was connected with low knowledge (RR: 5.67; 95% CI: 2.02-15.82, p<0.0002). The study confirms the crucial role of intensive insulin therapy and systematic patients' education concerning the disease in maintaining a good metabolic control and thus reducing the risk of diabetic vascular complications. PMID:15754632

  11. [Cost benefits of intensive insulin therapy using injections, external pumps and implantable pumps].

    PubMed

    Selam, J L; Haardt, M J; Berne, C; Dorange, C; Lanoe, J L; Bethoux, J P; Slama, G

    1993-12-01

    Since feasibility is now proven, cost-efficacy of external sub-cutaneous (EXT) and implantable programmable (IMP) insulin pumps needs to be compared to those of intensified conventional insulin therapy (CONV). Only metabolic efficacy and short-term direct costs are easily evaluable. We (WHO-CSII Study) and others have shown that glycemic control and severe hypoglycemia risk are slightly improved, while ketoacidosis risk and costs are aggravated with EXT vs CONV. We (CEDIT Study) and others have shown that glycemic control, mild and severe hypoglycemic risks are improved, with no increase in ketoacidosis rates although a doubling in costs with IMP vs CONV. Rigid interpretation of the above data would limit indications of insulin pumps to patients experiencing frequent hypoglycemias while on intensified conventional insulin therapy. PMID:8206188

  12. [Psychological aspects of remission induced by intensive insulin therapy in type I diabetes. A retrospective study of 44 patients].

    PubMed

    Ziegler, O; Kolopp, M; Kahn, J P; Floquet, B; Goudot, C; Beyel, P; Drouin, P; Debry, G

    1991-01-01

    The psychological consequences of induced remission of type 1 diabetes, have not yet been investigated thoroughly. We studied the psychological status of 44 patients (16 women, 28 men), age 21 years +/- 8 months (mean +/- SD), whose remission lasted 12 +/- 9 months. Patients' psychological reactions were analyzed retrospectively, using a 20 items standardized questionnaire, investigating 3 successive periods: 1) initial intensive insulin therapy; 2) remission; 3) permanent insulin therapy. 8% of the subjects only considered the remission phase useless, whereas 49% expressed a positive appraisal. Hope was predominant feeling, 25% of the patients believing in a completed recovery of diabetes. Perceived therapeutic constraints were, in decreasing order: regimen, way of life's regularity, self monitoring of blood glucose. When starting permanent insulin therapy, opposite answers were given: 49% negative feelings, 33% positive feelings and 18% ambivalent feelings. During this period, insulin injections represented the major therapeutic constraint, followed by self monitoring of blood glucose. To summarize, induced remission does not appear to be psychologically harmful and is considered useful by a large majority of patients. Effective psychological support has to be offered to help those patients to cope with their irrational hopes of healing and to dampen their deception at the end of the remission period. PMID:1752345

  13. Characteristics and effects of nurse dosing over-rides on computer-based intensive insulin therapy protocol performance

    PubMed Central

    May, Addison K; Waitman, Lemuel R; Ozdas, Asli; Lorenzi, Nancy M; Gadd, Cynthia S

    2011-01-01

    Objective To determine characteristics and effects of nurse dosing over-rides of a clinical decision support system (CDSS) for intensive insulin therapy (IIT) in critical care units. Design Retrospective analysis of patient database records and ethnographic study of nurses using IIT CDSS. Measurements The authors determined the frequency, direction—greater than recommended (GTR) and less than recommended (LTR)— and magnitude of over-rides, and then compared recommended and over-ride doses' blood glucose (BG) variability and insulin resistance, two measures of IIT CDSS associated with mortality. The authors hypothesized that rates of hypoglycemia and hyperglycemia would be greater for recommended than over-ride doses. Finally, the authors observed and interviewed nurse users. Results 5.1% (9075) of 179 452 IIT CDSS doses were over-rides. 83.4% of over-ride doses were LTR, and 45.5% of these were ≥50% lower than recommended. In contrast, 78.9% of GTR doses were ≤25% higher than recommended. When recommended doses were administered, the rate of hypoglycemia was higher than the rate for GTR (p=0.257) and LTR (p=0.033) doses. When recommended doses were administered, the rate of hyperglycemia was lower than the rate for GTR (p=0.003) and LTR (p<0.001) doses. Estimates of patients' insulin requirements were higher for LTR doses than recommended and GTR doses. Nurses reported trusting IIT CDSS overall but appeared concerned about recommendations when administering LTR doses. Conclusion When over-riding IIT CDSS recommendations, nurses overwhelmingly administered LTR doses, which emphasized prevention of hypoglycemia but interfered with hyperglycemia control, especially when BG was >150 mg/dl. Nurses appeared to consider the amount of a recommended insulin dose, not a patient's trend of insulin resistance, when administering LTR doses overall. Over-rides affected IIT CDSS protocol performance. PMID:21402737

  14. Evolving strategies for insulin delivery and therapy.

    PubMed

    Cefalu, William T

    2004-01-01

    It has now been conclusively proven that adequate control of blood glucose delays or prevents the progression of diabetic complications. In order to achieve the suggested targets for glycaemic control necessary to reduce the incidence of diabetic complications, it has been established that a more intensive insulin regimen requiring multiple insulin injections is required for patients with type 1 diabetes mellitus. For patients with type 2 diabetes, oral antidiabetic therapy is generally used initially, but given the natural history of type 2 diabetes and the need to achieve improved glycaemic control, earlier use of insulin has been promoted. However, the use of insulin in more intensive regimens for the patient with type 1 diabetes or for earlier treatment of the patient with type 2 diabetes is not routine. Many factors are responsible for this observation. Nevertheless, available device options such as insulin pens or insulin pumps are routinely available for implementation of intensive insulin therapy. However, a major limitation for advancing to intensive insulin therapy is that the only viable way to administer insulin is through injection. Delivery options that use dermal, nasal and oral approaches have been explored. The oral approach may include gastrointestinal, buccal or pulmonary uptake. Recent evidence shows that delivery of insulin via the oral cavity with uptake occurring in the pulmonary alveoli may be the most viable clinical option in the future. PMID:15161324

  15. [Insulin therapy of diabetes].

    PubMed

    Lechleitner, Monika; Roden, Michael; Weitgasser, Raimund; Ludvik, Bernhard; Fasching, Peter; Hoppichler, Friedrich; Kautzky-Willer, Alexandra; Schernthaner, Guntram; Prager, Rudolf; Wascher, Thomas C

    2016-04-01

    Hyperglycemia contributes to morbidity and mortality in patients with diabetes. Thus, reaching treatment targets with regard to control of glycemia is a central goal in the therapy of diabetic patients. The present article represents the recommendations of the Austrian Diabetes Association for the practical use of insulin according to current scientific evidence and clinical studies. PMID:27052221

  16. Insulin pump therapy in pregnancy.

    PubMed

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience. PMID:27582150

  17. Insulin therapy in type 2 diabetes.

    PubMed

    Mudaliar, S; Edelman, S V

    2001-12-01

    Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG

  18. Adherence to Insulin Therapy.

    PubMed

    Sarbacker, G Blair; Urteaga, Elizabeth M

    2016-08-01

    IN BRIEF Six million people with diabetes use insulin either alone or in combination with an oral medication. Many barriers exist that lead to poor adherence with insulin. However, there is an underwhelming amount of data on interventions to address these barriers and improve insulin adherence. Until pharmacological advancements create easier, more acceptable insulin regimens, it is imperative to involve patients in shared decision-making. PMID:27574371

  19. Insulin therapy in pregnancy.

    PubMed

    Kalra, Sanjay; Jawad, Fatema

    2016-09-01

    Insulin is the mainstay of pharmacotherapy in pregnancy complicated by diabetes. This review covers the various insulin regimes and preparations, explaining how to use them, and decide appropriate doses in pregnancy. It approaches insulin treatment from a patient - centred, as well as physician and obstetrician friendly viewpoint, providing pragmatic guidance for management of diabetes in pregnancy. PMID:27582152

  20. Comparison of a Multiple Daily Insulin Injection Regimen (Glargine or Detemir Once Daily Plus Prandial Insulin Aspart) and Continuous Subcutaneous Insulin Infusion (Aspart) in Short-Term Intensive Insulin Therapy for Poorly Controlled Type 2 Diabetes Patients

    PubMed Central

    Lv, Wen-shan; Li, Li; Wen, Jun-ping; Pan, Rong-fang; Sun, Rui-xia; Wang, Jing; Xian, Yu-xin; Cao, Cai-xia; Gao, Yan-yan

    2013-01-01

    Aims. To examine the potential differences between multiple daily injection (MDI) regimens based on new long-acting insulin analogues (glargine or detemir) plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII) in patients with poorly controlled type 2 diabetes. Methods. Patients (n = 119) with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes. PMID:23737776

  1. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes

    PubMed Central

    Kramer, Caroline K; Zinman, Bernard; Choi, Haysook; Retnakaran, Ravi

    2016-01-01

    Objective In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2–4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to 1 year in some patients. However, little is known about the predictors of such a sustained remission. Methods We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM. Results At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function (Insulin Secretion-Sensitivity Index-2) (p=0.01) that was then sustained across 48 weeks post-IIT (p=0.006). On logistic regression analyses, however, shorter duration of diabetes supplanted baseline A1c (p=0.24) and β-cell function (p=0.19) as an independent predictor of remission (p=0.04). In particular, diabetes duration <2 years predicted persistence of remission (p=0.006). Conclusions The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. Trial registration number ClinicalTrials.Gov NCT01270789; Post-results. PMID:27547422

  2. Insulin therapies: Current and future trends at dawn

    PubMed Central

    Yaturu, Subhashini

    2013-01-01

    Insulin is a key player in the control of hyperglycemia for type 1 diabetes patients and selective individuals in patients of type 2 diabetes. Insulin delivery systems that are currently available for the administration of insulin include insulin syringes, insulin infusion pumps, jet injectors and pens. The traditional and most predictable method for the administration of insulin is by subcutaneous injections. The major drawback of current forms of insulin therapy is their invasive nature. To decrease the suffering, the use of supersonic injectors, infusion pumps, sharp needles and pens has been adopted. Such invasive and intensive techniques have spurred the search for alternative, more acceptable methods for administering insulin. Several non-invasive approaches for insulin delivery are being pursued. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral and pulmonary routes. This review focuses on the new concepts that are being explored for use in future. PMID:23493823

  3. Insulin therapies: Current and future trends at dawn.

    PubMed

    Yaturu, Subhashini

    2013-02-15

    Insulin is a key player in the control of hyperglycemia for type 1 diabetes patients and selective individuals in patients of type 2 diabetes. Insulin delivery systems that are currently available for the administration of insulin include insulin syringes, insulin infusion pumps, jet injectors and pens. The traditional and most predictable method for the administration of insulin is by subcutaneous injections. The major drawback of current forms of insulin therapy is their invasive nature. To decrease the suffering, the use of supersonic injectors, infusion pumps, sharp needles and pens has been adopted. Such invasive and intensive techniques have spurred the search for alternative, more acceptable methods for administering insulin. Several non-invasive approaches for insulin delivery are being pursued. The newer methods explored include the artificial pancreas with closed-loop system, transdermal insulin, and buccal, oral and pulmonary routes. This review focuses on the new concepts that are being explored for use in future. PMID:23493823

  4. Increased 1,5-Anhydroglucitol Predicts Glycemic Remission in Patients with Newly Diagnosed Type 2 Diabetes Treated with Short-Term Intensive Insulin Therapy

    PubMed Central

    Liu, Liehua; Wan, Xuesi; Liu, Juan; Huang, Zhimin; Cao, Xiaopei

    2012-01-01

    Abstract Background Short-term intensive insulin therapy has been shown to induce long-term glycemic remission in patients with newly diagnosed type 2 diabetes. However, predictors of remission are still uncertain. This study was conducted to evaluate whether changes of 1,5-anhydroglucitol (1,5AG) and fructosamine (FA) could be a predictor of remission. Subjects and Methods Newly diagnosed drug-naive patients with type 2 diabetes (n=64) were enrolled. After baseline assessments, continuous subcutaneous insulin infusion (CSII) was administered in all patients until euglycemia was achieved and maintained for another 2 weeks. Patients were subsequently followed monthly for 3 months. 1,5AG and FA were measured before and after therapy and at 1-month follow-up. Results After CSII, A1C and FA decreased from baseline, whereas 1,5AG increased. 1,5AG was higher at 1-month follow-up (11.5±4.1 vs. 6.7±2.8 mg/L, P<0.001), whereas FA was lower (273.1±56.1 vs. 316.2±39.3 μmol/L, P=0.021) in the remission group. Stepwise logistic regression analysis showed that 1,5AG at 1-month follow-up rather than FA was an independent predictor of remission after adjusting for other confounders (odds ratio 1.56, 95% confidence interval [CI] 1.15–2.12, P=0.004). The area under the curve of the receiver operating characteristic curve analysis was 0.85 (95% CI 0.75–0.96, P<0.001). The optimal cutoff point for 1,5AG at 1-month follow-up was 8.9 mg/L (specificity, 83.3%; sensitivity, 78.6%). Conclusions Improvement of 1,5AG predicts maintenance of glycemic remission after intensive insulin therapy in patients with newly diagnosed type 2 diabetes. PMID:22731793

  5. Misadventures in insulin therapy: are you at risk?

    PubMed

    Grissinger, Matthew; Lease, Michael

    2003-02-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  6. Misadventures in insulin therapy: are you at risk?

    PubMed Central

    Grissinger, Matthew; Lease, Michael

    2003-01-01

    About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

  7. Insulin therapy in critically ill patients

    PubMed Central

    Ellahham, Samer

    2010-01-01

    Hyperglycemia frequently occurs with acute medical illness, especially among patients with cardiovascular disease, and has been linked to increased morbidity and mortality in critically ill patients. Even patients who are normoglycemic can develop hyperglycemia in response to acute metabolic stress. An expanding body of literature describes the benefits of normalizing hyperglycemia with insulin therapy in hospitalized patients. As a result, both the American Diabetes Association and the American College of Endocrinology have developed guidelines for optimal control of hyperglycemia, specifically targeting critically ill, hospitalized patients. Conventional blood glucose values of 140–180 mg/dL are considered desirable and safely achievable in most patients. More aggressive control to <110 mg/dL remains controversial, but has shown benefits in certain patients, such as those in surgical intensive care. Intravenous infusion is often used for initial insulin administration, which can then be transitioned to subcutaneous insulin therapy in those patients who require continued insulin maintenance. This article reviews the data establishing the link between hyperglycemia and its risks of morbidity and mortality, and describes strategies that have proven effective in maintaining glycemic control in high-risk hospitalized patients. PMID:21191429

  8. [Evidence based therapy with insulin in diabetic patients].

    PubMed

    Jermendy, György

    2005-02-20

    A fast development in therapy with insulin was observed after its discovery. Besides the widely used human regular insulin preparations, nowadays ultrashort and long-acting insulin analogues are also available for the patients. At present, the results of large clinical trials enable an evidence based diabetes care. It is well documented, that near-normoglycemia should be achieved by intensive conservative insulin treatment or pump therapy in type 1 diabetic patients. The beneficial effects of the good metabolic control could also be observed years later concerning late specific complications of diabetes. Similarly, as good as possible metabolic control should be aimed with antidiabetic treatment including insulin, if necessary, in type 2 diabetic patients. It is documented that the risk of cardiovascular complications is not increased in type 2 diabetic patients treated with insulin. Hypoglycemia and weight gain are the most important side effects of the insulin treatment. Recently, evidence based recommendations for treatment with ultrashort (insulin lispro, insulin aspart) and long-acting insulin analogues (glargine) can also be determined. PMID:15803885

  9. Predisposing Factors for Hypoglycemia and Its Relation With Mortality in Critically Ill Patients Undergoing Insulin Therapy in an Intensive Care Unit

    PubMed Central

    Mahmoodpoor, Ata; Hamishehkar, Hadi; Beigmohammadi, Mahammadtaghi; Sanaie, Sarvin; Shadvar, Kamran; Soleimanpour, Hassan; Rahimi, Ahsan; Safari, Saeid

    2016-01-01

    Background: Hypoglycemia is a common and the most important complication of intensive insulin therapy in critically ill patients. Because of hypoglycemia’s impact on the cardinal organs as a fuel, if untreated it could results in permanent brain damage and increased mortality. Objectives: In this study, we aim to evaluate the incidence of hypoglycemia, its risk factors, and its relationship with mortality in critically ill patients. Patients and Methods: Five hundred adult patients who admitted to an intensive care unit (ICU) were enrolled in this study. A program of glycemic control with a target of 100 - 140 mg/dL was instituted. We used the threshold of 150 mg/dL for septic patients, which were monitored by point of care devices for capillary blood measurement. We detected hypoglycemia with a blood sugar of less than 50 mg/dL and with the detection of each episode of hypoglycemia, blood glucose measurement was performed every 30 minutes. Results: Five hundred patients experienced at least one episode of hypoglycemia, almost always on the third day. Of 15 expired patients who had one hypoglycemia episode, the most common causes were multiple trauma and sepsis. Increases in the sequential organ failure assessment (SOFA) number augmented the hypoglycemia risk to 52% (P < 0.001). Moreover, in patients with acute kidney injury (AKI), the risk of hypoglycemia is 10 times greater than in those without AKI (RR: 10.3, CI: 3.16 - 33.6, P < 0.001). ICU admission blood sugar has a significant relationship with mortality (RR: 1.01, CI: 1.004 - 1.02, P < 0.006). Hypoglycemia increased the mortality rate twofold, but it was not significant (RR: 1.2, CI: 0.927 - 1.58, P = 0.221). Conclusions: Our results showed that the SOFA score, AKI, and hemoglobin A1c are the independent risk factors for the development of hypoglycemia and demonstrated that ICU admission blood glucose, Hba1c, and hypoglycemia increased the risk of death, but only ICU admission blood glucose is

  10. [Intensified insulin therapy and insulin micro-pumps during pregnancy].

    PubMed

    Galuppi, V

    1994-06-01

    Before conception and during pregnancy in diabetic patients, every possible effort should be made in order to obtain a good, if not perfect, metabolic control and to warrant maternal and fetal health. Multiple daily injections are required to achieve a very strict glucose regulation in pregnant patients with insulin-dependent diabetes mellitus. The most usual intensive insulin administration patterns require 3 premeal doses of short-acting insulin and 1 (at bedtime) or 2 (one in the morning and one at bedtime) injections of intermediate or slow-acting insulin. As an alternative choice, insulin pumps allow a continuous subcutaneous infusion with short-acting insulin according to a basal rate which cover the insulin need during the night and between meals. Premeal and presnack surges of insulin are administrated by the patient herself. Home glucose monitoring must be used to adjust insulin doses. Target glucose levels every diabetic pregnant woman should try to achieve are lower than in non-pregnant women: fasting glycaemia should be below 100 mg/dl, 1 hour post-prandial value below 140 mg/dl and 2 hour post-prandial level below 120 mg/dl. The stricter the control and treatment goals are, the more frequently hypoglycaemia may occur. Hypoglycaemia may be harmful especially for patients with severe diabetic complications and may affect the fetus. Therefore, every pregnant diabetic woman should receive individualized treatment and glycaemic goals according to her clinical features, her compliance and her social and cultural background. PMID:7968932

  11. Intensity modulated proton therapy

    PubMed Central

    Grassberger, C

    2015-01-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak—the characteristic peak of dose at the end of range—combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose “painting” within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the

  12. Intensity modulated proton therapy.

    PubMed

    Kooy, H M; Grassberger, C

    2015-07-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed "pencil beams" of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak-the characteristic peak of dose at the end of range-combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose "painting" within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the highest level of

  13. Short acting insulin analogues in intensive care unit patients

    PubMed Central

    Bilotta, Federico; Guerra, Carolina; Badenes, Rafael; Lolli, Simona; Rosa, Giovanni

    2014-01-01

    Blood glucose control in intensive care unit (ICU) patients, addressed to actively maintain blood glucose concentration within defined thresholds, is based on two major therapeutic interventions: to supply an adequate calories load and, when necessary, to continuously infuse insulin titrated to patients needs: intensive insulin therapy (IIT). Short acting insulin analogues (SAIA) have been synthesized to improve the chronic treatment of patients with diabetes but, because of the pharmacokinetic characteristics that include shorter on-set and off-set, they can be effectively used also in ICU patients and have the potential to be associated with a more limited risk of inducing episodes of iatrogenic hypoglycemia. Medical therapies carry an intrinsic risk for collateral effects; this can be more harmful in patients with unstable clinical conditions like ICU patients. To minimize these risks, the use of short acting drugs in ICU patients have gained a progressively larger room in ICU and now pharmaceutical companies and researchers design drugs dedicated to this subset of medical practice. In this article we report the rationale of using short acting drugs in ICU patients (i.e., sedation and treatment of arterial hypertension) and we also describe SAIA and their therapeutic use in ICU with the potential to minimize iatrogenic hypoglycemia related to IIT. The pharmacodynamic and pharmachokinetic characteristics of SAIA will be also discussed. PMID:24936244

  14. Hypoglycaemia, the most feared complication of insulin therapy.

    PubMed

    McCrimmon, R J; Frier, B M

    1994-01-01

    Insulin-induced hypoglycaemia, the most frequent side-effect of insulin-therapy, is a potential source of considerable morbidity and has a recognised mortality. Acute hypoglycaemia produces an intense physiological stress with profound sympathoadrenal stimulation and widespread activation of hormonal counterregulatory systems, leading to secondary haemodynamic and haemorheological changes. The clinical effects of acute and recurrent severe hypoglycaemia are associated with significant morbidity including reversible, and permanent, abnormalities of cardiovascular, neurological and cognitive function, in addition to trauma and road traffic accidents. Comprehension of the morbidity of hypoglycaemia is important when designing insulin regimens and determining therapeutic goals for individual patients if the frequency and adverse effects of this dangerous side-effect of insulin therapy are to be limited. PMID:7713272

  15. [Insulin resistance - its causes and therapy possibilities].

    PubMed

    Pelikánová, Terezie

    2014-09-01

    Insulin resistance (IR) is defined as a condition where normal plasma free insuconcentrations induce a reduced response of the body. In the narrower sense we understand IR as the impairment of insulin action in the target structure which may arise at any level of the insulin signalling cascade. In the clinical conditions we usually define it as the impairment of insulin action in glucose metabolism, although it is true that the impairment may concern different effects of insulin and different cell structures. The characteristic feature of IR linked to the metabolic syndrome or Type 2 diabetes is defective signalling which affects PI3-kinase branch of insulin signalling cascade. Other insulin actions depending on the signalling through the Ras complex and MAP-kinase, may not be affected. Due to compensatory hyperinsulinemia they may be even increased. The article summarizes some recent findings regarding the structure and regulation of insulin signalling cascade and analyses selected primary and secondary causes of IR which include genetic and epigenetic factors, the microRNA regulation role, metabolic, humoral and immunological factors. The detailed knowledge of the causes of IR opens possibilities of its rational treatment. This is currently based on the treatment of curable causes of IR, i.e. consistent compensation of diabetes, weight reduction, regimen arrangements (diet, physical activity), re-assessment of the need to use corticosteroids in therapy, treatment of coexisting conditions and possibly administration of metformin or pioglitazone.Key words: cytokines - insulin resistance - insulin signalling cascade. PMID:25294764

  16. Initiating insulin therapy in type 2 diabetes: benefits of insulin analogs and insulin pens.

    PubMed

    Brunton, Stephen

    2008-08-01

    Despite the development of alternative therapies in recent years, insulin injections remain essential treatment for type 2 diabetes once oral therapy alone becomes inadequate. However, neither patients nor physicians are proactive enough with regard to starting insulin, despite the well-known benefits of early insulin initiation and aggressive dose titration. Barriers to starting insulin therapy are being overcome by developments in insulin and delivery device technology and are the subject of this review. A literature search spanning the last 25 years was carried out to identify publications addressing issues of insulin initiation, how insulin analogs can help overcome barriers to initiation, and the advantages of pen-type insulin delivery systems. Seventy-five publications were identified. These references illustrate that the drawbacks associated with regular exogenous human insulins (soluble and NPH) are improved with modern insulin analogs. The more rapid absorption of prandial insulin analogs compared with human insulin eliminates the need for an injection-meal-interval, increasing convenience, while basal analogs have no discernible peak in activity. Modern insulin delivery devices also have advantages over the traditional vial and syringe. Currently available insulin pens are either durable (insulin cartridge is replaceable; e.g., HumaPen, Eli Lilly [Indianapolis, IN]; NovoPen series, Novo Nordisk [Bagsvaerd, Denmark]) or disposable (prefilled; e.g., FlexPen, Novo Nordisk; SoloSTAR, sanofi-aventis [Paris, France]), with features to aid ease-of-use. These include a large dose selector, dial-up and dial-down facility, and audible clicks when selecting the dose. The potential for dosing errors is thus reduced with pen-type devices, with other benefits including a discreet appearance, ease of learning, and greater user confidence. Collectively, these features contribute to overwhelming patient preference when compared with vials and syringes. Despite the greater

  17. [Current concept of insulin therapy intensification, and the role of human regular insulin and rapid-acting insulin analogs in insulin treatment].

    PubMed

    Hamaguchi, Tomoya; Sadahiro, Katsuhiko; Satoh, Tomomi

    2015-03-01

    The evolution of insulin therapy from animal insulin to recombinant human regular insulin has improved diabetes treatment. Generating of rapid-acting insulin analogs, mimicking physiologic insulin action enables us to provide better control of post-prandial glucose level and lower incidence of hypoglycemia compared with human regular insulin. These rapid-acting insulin analogs show lower susceptibility of insulin precipitation and catheter occlusions, and are suitable for insulin pump therapy of continuous subcutaneous insulin infusion. Insulin lispro and insulin aspart are also applicable for diabetic patients with pregnancy, requiring excellent glycemic control. In some studies, stepwise addition of prandial insulin, as well as full basal-bolus regimen can improve glycemic control with less hypoglycemia. Treatment intensification with rapid-acting insulin analogs may offer a proper method to reach glycemic goals. PMID:25812371

  18. [Insulin therapy for type 1 diabetes mellitus: past and present].

    PubMed

    Pires, Antonio Carlos; Chacra, Antonio Roberto

    2008-03-01

    The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells. PMID:18438537

  19. Intensifying Insulin Therapy in Type 2 Diabetes: Choices & Challenges.

    PubMed

    Kumar, Ajay; Kesavadev, Jothydev; Sethi, Bipin; Jain, Sunil M; Guruprasad, C S; Shah, Siddharth N

    2015-05-01

    Insulin therapy remains the cornerstone of effective diabetes management. Timely intensification of insulin therapy reduces the progression of diabetes and the development of diabetes-related complications. Given that overall hyperglycaemia is a relative contribution of both fasting and postprandial hyperglycaemia, use of basal insulin alone may not achieve optimal glucose control due to its inability to cover postprandial glucose excursions. Intensifying therapy with addition of bolus insulin or switching to premixed insulin is a viable option in patients failing on basal alone therapy. Although the benefits of early insulin treatment are well established, a considerable delay in intensifying insulin therapy in patients with sub-optimal glycaemic control is still observed. Most of the patients and physicians are reluctant to intensify therapy due to the fear of hypoglycaemia, regimen complexity, and increased burden of multiple daily injections. In this context, there is a need for a flexible, alternative intensification option taking into account individual patient considerations to achieve or maintain individual glycaemic targets. An ideal insulin regimen should mimic physiological insulin release while providing optimal glycaemic control with low risk of hypoglycaemia, weight gain and fewer daily injections. The current paper reviews the challenges of insulin intensification in patients with type 2 diabetes mellitus poorly controlled on current treatment regimens. PMID:26548029

  20. Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy

    NASA Astrophysics Data System (ADS)

    Heise, H. Michael; Kondepati, Venkata Radhakrishna; Damm, Uwe; Licht, Michael; Feichtner, Franz; Mader, Julia Katharina; Ellmerer, Martin

    2008-02-01

    Implementing strict glycemic control can reduce the risk of serious complications in both diabetic and critically ill patients. For this purpose, many different blood glucose monitoring techniques and insulin infusion strategies have been tested towards the realization of an artificial pancreas under closed loop control. In contrast to competing subcutaneously implanted electrochemical biosensors, microdialysis based systems for sampling body fluids from either the interstitial adipose tissue compartment or from venous blood have been developed, which allow an ex-vivo glucose monitoring by mid-infrared spectrometry. For the first option, a commercially available, subcutaneously inserted CMA 60 microdialysis catheter has been used routinely. The vascular body interface includes a double-lumen venous catheter in combination with whole blood dilution using a heparin solution. The diluted whole blood is transported to a flow-through dialysis cell, where the harvesting of analytes across the microdialysis membrane takes place at high recovery rates. The dialysate is continuously transported to the IR-sensor. Ex-vivo measurements were conducted on type-1 diabetic subjects lasting up to 28 hours. Experiments have shown excellent agreement between the sensor readout and the reference blood glucose concentration values. The simultaneous assessment of dialysis recovery rates renders a reliable quantification of whole blood concentrations of glucose and metabolites (urea, lactate etc) after taking blood dilution into account. Our results from transmission spectrometry indicate, that the developed bed-side device enables reliable long-term glucose monitoring with reagent- and calibration-free operation.

  1. Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

    PubMed Central

    McDonnell, Marie E.; Umpierrez, Guillermo E.

    2013-01-01

    It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

  2. A randomized controlled trial of liraglutide versus insulin detemir plus sitagliptin: Effective switch from intensive insulin therapy to the once-daily injection in patients with well-controlled type 2 diabetes.

    PubMed

    Inoue, Yuichiro; Nakamura, Akinobu; Kondo, Yoshinobu; Hamano, Kumiko; Satoh, Shinobu; Terauchi, Yasuo

    2015-07-01

    This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal-bolus insulin regimen. In this multicenter, open-label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c ] ≤ 7.3%) with basal-bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The "overall" satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal-bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control. PMID:25677642

  3. [Insulin pump therapy in children, adolescents and adults].

    PubMed

    Stadler, Marietta; Zlamal-Fortunat, Sandra; Schütz-Fuhrmann, Ingrid; Rami-Merhar, Birgit; Fröhlich-Reiterer, Elke; Hofer, Sabine; Mader, Julia; Resl, Michael; Kautzky-Willer, Alexandra; Weitgasser, Raimund; Prager, Rudolf; Bischof, Martin

    2016-04-01

    This position statement is based on the current evidence available on the safety and benefits of continuous subcutaneous insulin pump therapy (CSII) in diabetes with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occurrence of ketoacidosis, quality of life and the use of insulin pump therapy in pregnancy. The current article represents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treatment in children, adolescents and adults. PMID:27052245

  4. Intraperitoneal insulin therapy for a patient with type 1 diabetes with insulin injection site inflammation.

    PubMed

    Lee, Siang Ing; Narendran, Parth

    2014-01-01

    A 36-year-old man with type 1 diabetes developed skin inflammation at the site of subcutaneous insulin injection after 10 years of basal bolus subcutaneous insulin therapy. This inflammation led to poor insulin absorption, poorly controlled blood glucose and subsequently to ketoacidosis. The problem persisted despite a trial of continuous subcutaneous insulin infusion. The patient went on to be treated with continuous intraperitoneal insulin infusion. Three months after the procedure, he was achieving good glucose control and was able to resume his normal life, with the only complication being an episode of cellulitis surrounding the port site. PMID:25188930

  5. Intraperitoneal insulin therapy for a patient with type 1 diabetes with insulin injection site inflammation

    PubMed Central

    Lee, Siang Ing; Narendran, Parth

    2014-01-01

    A 36-year-old man with type 1 diabetes developed skin inflammation at the site of subcutaneous insulin injection after 10 years of basal bolus subcutaneous insulin therapy. This inflammation led to poor insulin absorption, poorly controlled blood glucose and subsequently to ketoacidosis. The problem persisted despite a trial of continuous subcutaneous insulin infusion. The patient went on to be treated with continuous intraperitoneal insulin infusion. Three months after the procedure, he was achieving good glucose control and was able to resume his normal life, with the only complication being an episode of cellulitis surrounding the port site. PMID:25188930

  6. Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

    PubMed Central

    Ribeiro, Maria Estela Bellini; Liberatore, Raphael Del Roio; Custodio, Rodrigo; Martinelli, Carlos Eduardo

    2016-01-01

    Abstract Objective: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods: 40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Results: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. Conclusions: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. PMID:26826879

  7. Insulin therapy: going the "smarter" way.

    PubMed

    Kalra, Sanjay; Joshi, Ameya; Parmar, Girish

    2014-01-01

    Insulin pharmacology has evolved from nonhuman source based extraction of insulin, to use of recombinant technologies for human insulin production, to tailor made synthetic insulin analogues. The delivery techniques of insulin have also improved, from injections to pumps, and to pumps with sensors. However, to achieve the final goal of a closed loop insulin delivery is far from achieved. One of the researches in this direction includes synthetic smart insulins. These are systems with chemical sensors for glucose, linked to reactions that trigger glucose mediated insulin delivery. Interest in this field is high and recent publications and patents show promise. The current review tries to summarize the basic concept of smart insulin as well as cater the recent developments and patents in this direction. PMID:24975640

  8. Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

    PubMed Central

    2014-01-01

    Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

  9. Engineering Synthetically Modified Insulin for Glucose-Responsive Diabetes Therapy

    PubMed Central

    Webber, Matthew J.; Anderson, Daniel G.; Langer, Robert

    2016-01-01

    Summary Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy.

  10. Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

    PubMed

    Sigal, R J; Purdon, C; Fisher, S J; Halter, J B; Vranic, M; Marliss, E B

    1994-10-01

    insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise. PMID:7962273

  11. The Role of Comfort and Discomfort in Insulin Therapy

    PubMed Central

    2012-01-01

    Abstract Despite the recognized importance of optimal insulin therapy, patient adherence to insulin therapy is an ongoing clinical care challenge. Insulin omission continues to be frequent and underestimated and has been correlated with poorer glycemic control and increased rates of diabetes-related complications. Insulin users consistently indentify multiple factors that contribute to insulin injection-related anxiety and to non-adherence. Injection-related discomfort continues to bear a significant contribution. Over the last decade, with advances in needle manufacturing technology, shorter and narrower needles have been associated with progressively improving patient self-rating of injection discomfort. Consequently, patient surveys of insulin users show discomfort to rank in the bottom third of significant contributors by prevalence. However, healthcare providers (HCP) and family member care providers continue to demonstrate a high level of anticipated and perceived pain for the patient. HCP anxiety and pain anticipation are each associated with patient anxiety and may therefore play a significant contributing role in patient non-adherence. PMID:22537418

  12. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    NASA Astrophysics Data System (ADS)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  13. Non-insulin pharmacological therapy in pregnancy.

    PubMed

    Bajaj, Sarita

    2016-09-01

    During pregnancy, when glycaemic levels remain uncontrolled, despite lifestyle modification, pharmacotherapy is advised, usually insulin which has been the gold standard for treatment. Recent studies however suggest that certain oral anti diabetic agents (OADs) may be safe and acceptable alternatives. There may be potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and foetus. Glibenclamide, a second generation sulfonylurea, more effective in glycaemic control in women with GDM has a lower treatment failure rate than metformin but there is lack of long term follow up data. Even though generally well tolerated, some studies report higher rates of preeclampsia, macrosomia, neonatal jaundice, neonatal hypoglycaemia and longer stay in neonatal care unit. PMID:27582151

  14. Myostatin inhibition therapy for insulin-deficient type 1 diabetes.

    PubMed

    Coleman, Samantha K; Rebalka, Irena A; D'Souza, Donna M; Deodhare, Namita; Desjardins, Eric M; Hawke, Thomas J

    2016-01-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with Myostatin(Ln/Ln) mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. PMID:27581061

  15. Myostatin inhibition therapy for insulin-deficient type 1 diabetes

    PubMed Central

    Coleman, Samantha K.; Rebalka, Irena A.; D’Souza, Donna M.; Deodhare, Namita; Desjardins, Eric M.; Hawke, Thomas J.

    2016-01-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. PMID:27581061

  16. Replanning of an intensive therapy unit

    PubMed Central

    Ryan, D W; Copeland, P F; Miller, J; Freeman, R

    1982-01-01

    Considerable effort is needed when replanning an intensive therapy unit to avoid repeating mistakes in design, such as lack of windows and an impractical working area. Early consultation with the nursing and medical staff primarily responsible for such a unit is essential. The considerable technological innovations in intensive care will require flexibility in the future if they are to be incorporated into existing facilities. ImagesFIG 2FIG 4 PMID:6814684

  17. The importance of postprandial glycemic control: optimizing add-on therapy to basal insulin.

    PubMed

    Shaefer, Charles F; Anderson, John

    2016-01-01

    Diabetes, mainly type 2 diabetes mellitus (T2DM), is associated with a growing clinical and economic burden in the United States, which is expected to increase in association with an aging population. Sufficient glycemic control in patients with T2DM, in order to reduce the risk of micro- and macrovascular complications associated with diabetes, is mediated by lifestyle modifications and a regimen of increasingly intensive antidiabetes drugs. Several treatments and strategies are available for primary care physicians to select from when choosing the most appropriate therapy for their individual patients with T2DM, but, ultimately, due to the progressive nature of the disease, most of these patients will require insulin therapy to maintain glycemic control. Regimens containing basal and postprandial insulins are widely used, but there is still widespread reluctance to initiate insulin treatment due to fear of weight gain and hypoglycemia. Furthermore, as patients approach recommended glycated hemoglobin targets, postprandial hyperglycemia becomes the main contributor to hyperglycemic exposure, necessitating the timely initiation of prandial treatment. Finally, insulin treatment can be limited by factors like the number of injections, mealtime restrictions, complex titration algorithms and patient adherence. Recent developments in antidiabetes drug research have brought more convenient basal and postprandial regimens closer. Clinical evaluation of the efficacy and safety of basal insulins plus add-on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has yielded promising results. Primary care physicians are continually challenged to optimize insulin treatment strategies to maximize patient outcomes. Emerging strategies such as long-acting basal insulin analogs and short-acting GLP-1 RAs are particularly appealing to address this challenge. PMID:26548422

  18. Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes.

    PubMed

    Sharma, Garima; Sharma, Ashish Ranjan; Nam, Ju-Suk; Doss, George Priya C; Lee, Sang-Soo; Chakraborty, Chiranjib

    2015-01-01

    Diabetic cases have increased rapidly in recent years throughout the world. Currently, for type-1 diabetes mellitus (T1DM), multiple daily insulin (MDI) injections is the most popular treatment throughout the world. At this juncture, researchers are trying to develop different insulin delivery systems, especially through oral and pulmonary route using nanocarrier based delivery system. This next generation efficient therapy for T1DM may help to improve the quality of life of diabetic patients who routinely employ insulin by the subcutaneous route. In this paper, we have depicted various next generation nanocarrier based insulin delivery systems such as chitosan-insulin nanoparticles, PLGA-insulin nanoparticles, dextran-insulin nanoparticles, polyalkylcyanoacrylated-insulin nanoparticles and solid lipid-insulin nanoparticles. Modulation of these insulin nanocarriers may lead to successful oral or pulmonary insulin nanoformulations in future clinical settings. Therefore, applications and limitations of these nanoparticles in delivering insulin to the targeted site have been thoroughly discussed. PMID:26498972

  19. Exercise Intensity Modulates Glucose-Stimulated Insulin Secretion when Adjusted for Adipose, Liver and Skeletal Muscle Insulin Resistance

    PubMed Central

    Malin, Steven K.; Rynders, Corey A.; Weltman, Judy Y.; Barrett, Eugene J.; Weltman, Arthur

    2016-01-01

    Little is known about the effects of exercise intensity on compensatory changes in glucose-stimulated insulin secretion (GSIS) when adjusted for adipose, liver and skeletal muscle insulin resistance (IR). Fifteen participants (8F, Age: 49.9±3.6yr; BMI: 31.0±1.5kg/m2; VO2peak: 23.2±1.2mg/kg/min) with prediabetes (ADA criteria, 75g OGTT and/or HbA1c) underwent a time-course matched Control, and isocaloric (200kcal) exercise at moderate (MIE; at lactate threshold (LT)), and high-intensity (HIE; 75% of difference between LT and VO2peak). A 75g OGTT was conducted 1 hour post-exercise/Control, and plasma glucose, insulin, C-peptide and free fatty acids were determined for calculations of skeletal muscle (1/Oral Minimal Model; SMIR), hepatic (HOMAIR), and adipose (ADIPOSEIR) IR. Insulin secretion rates were determined by deconvolution modeling for GSIS, and disposition index (DI; GSIS/IR; DISMIR, DIHOMAIR, DIADIPOSEIR) calculations. Compared to Control, exercise lowered SMIR independent of intensity (P<0.05), with HIE raising HOMAIR and ADIPOSEIR compared with Control (P<0.05). GSIS was not reduced following exercise, but DIHOMAIR and DIADIPOSEIR were lowered more following HIE compared with Control (P<0.05). However, DISMIR increased in an intensity based manner relative to Control (P<0.05), which corresponded with lower post-prandial blood glucose levels. Taken together, pancreatic insulin secretion adjusts in an exercise intensity dependent manner to match the level of insulin resistance in skeletal muscle, liver and adipose tissue. Further work is warranted to understand the mechanism by which exercise influences the cross-talk between tissues that regulate blood glucose in people with prediabetes. PMID:27111219

  20. Chromium Therapy for Insulin Resistance Associated with HIV-Disease

    PubMed Central

    Stein, Seth A; Mc Nurlan, Margaret; Phillips, Brett T; Messina, Catherine; Mynarcik, Dennis; Gelato, Marie

    2014-01-01

    Objective With the advent of highly active anti-retroviral therapy, HIV disease has become a chronic condition, but with a number of metabolic complications including insulin resistance and diabetes mellitus, dyslipidemia and hypertension and an increased incidence of atherosclerosis. The aim of the current study was to test the safety and efficacy of chromium picolinate for HIV- associated insulin resistance. Materials/Methods The study was a randomized, double-blind, placebo-controlled trial with subjects receiving 500μg of chromium picolinate or placebo twice daily for two months. HIV- infected subjects were selected based on a fasting concentration of plasma glucose greater than 5.5mmol/L or a plasma glucose concentration of greater than 7.7mmol/L (but less than 11mmol/L) 2h after oral ingestion of 75g of glucose. Insulin sensitivity was assessed with a hyper-insulinemic-euglycemic clamp and glucose tolerance was assessed with the oral glucose tolerance test. Subjects were monitored closely for alterations in viral load, CD4+ cells, hemoglobin and hematocrit, kidney and liver function, and fasting lipid profiles. Results Forty-three subjects were enrolled and 39 completed the protocol (20 in the chromium-supplemented and 19 in the placebo arm). Following chromium-supplementation, there were no significant changes in either insulin sensitivity or glucose tolerance. There was a significant improvement in serum HDL cholesterol concentration in the group supplemented with chromium. Conclusions Chromium picolinate supplementation at this level was well-tolerated, but overall was not an effective therapy for insulin resistance in these HIV-infected subjects. PMID:25346863

  1. Interaction between plastic catheter tubings and regular insulin preparations used for continuous subcutaneous insulin-infusion therapy.

    PubMed

    Chantelau, E; Lange, G; Gasthaus, M; Boxberger, M; Berger, M

    1987-01-01

    In search of possible interactions between plastic tubings used for insulin-pump treatment and commercial regular insulin preparations, various catheter sets made from polyvinyl chloride (PVC), polyethylene (PE), and nylon plastics were perfused at 30 degrees C in a laboratory setting for up to 72 h. The perfused insulin solutions were analyzed by high-performance liquid chromatography and atomic absorption spectroscopy. Although no plasticizer, e.g., dioctyl phthalate, or nickel or chromium ions were found in the perfusates, substantial interactions between the plastics and the insulin solutions were detected, extraction of bacteriostatic additives from the insulin solutions in particular. The PVC retained up to 88% of the bacteriostatics from the insulin preparations, whereas PE tubings retained only 10-15%. Whether the loss of preservatives during perfusion through PVC catheters predisposes to cutaneous infections during insulin-pump therapy remains to be shown. PMID:3297580

  2. Problems of intensive therapy in childhood cancer

    SciTech Connect

    Skelton, J.; Pizzo, P.A.

    1986-07-15

    Tremendous progress has been made in the treatment of childhood cancers. Certain hematologic malignancies have an impressive cure rate with the current intensive antineoplastic treatment regimens. There is optimism that the treatment of children who have advanced stage solid tumors with intensive, multimodality therapy may improve their chances for long-term survival. These treatment programs, though potentially curative, are highly toxic, with severe myelosuppression and damage to other organ systems. An awareness of these potential toxicities, an understanding of how to prevent or minimize certain problems, and the ability to treat those complications which do arise are all essential to the successful management of childhood cancer. 206 references.

  3. Effects of Prior Intensive Insulin Therapy and Risk Factors on Visual Quality-of-Life in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Cohort

    PubMed Central

    Gubitosi-Klug, Rose A.; Sun, Wanjie; Cleary, Patricia A.; Braffett, Barbara H.; Aiello, Lloyd Paul; Das, Arup; Tamborlane, William; Klein, Ronald

    2016-01-01

    glycemic control in DCCT (explained treatment effect: 100%). Those with VA worse than 20/100 reported the lowest VQOL score. Conclusions and Relevance In the DCCT/EDIC cohort, VQOL remains high in both treatment groups. Intensive diabetes therapy modestly improved VQOL 30 years after the start of the DCCT. VA had the greatest impact on VQOL from among all risk factors. PMID:26584339

  4. [Relationship of insulin dependent metabolic disorders to efficiency of intensive operator's work].

    PubMed

    Petrova, T V; Bobrovnitskiĭ, I P; Vashchilo, B A; Orlova, T A

    2002-01-01

    The purpose was to state correlation between insulin-dependent metabolic disorders and efficiency of intensive operator's work. The investigation included 12-hr mission on a flight simulator performed by 50 normal (aged 23-36) flight-qualified pilots. Increase in the number of erroneous actions was in direct correlation with insulin (r = 0.74, p < 0.01) and in reverse correlation with glucose incretion (r = -0.594, p < 0.01) and STH (r = -0.90, p < 0.006). Metabolic tests (glucose and insulin) showed that psychoemotional loading due to the intensive operator's duties led to early fatigue and sharp straining of tissue structures in people with dysregulatory disorders in insulin metabolism. The psychoemotional loading may also provoke dysregulatory disorders and development of insulin-dependent disturbances. PMID:12572118

  5. The Insulin Receptor: A New Target for Cancer Therapy

    PubMed Central

    Malaguarnera, Roberta; Belfiore, Antonino

    2011-01-01

    A large body of evidences have shown that both the IGF-I receptor (IGF-IR) and the insulin receptor (IR) play a role in cancer development and progression. In particular, IR overactivation by IGF-II is common in cancer cells, especially in dedifferentiated/stem-like cells. In spite of these findings, until very recently, only IGF-IR but not IR has been considered a target in cancer therapy. Although several preclinical studies have showed a good anti-cancer activity of selective anti-IGF-IR drugs, the results of the clinical first trials have been disappointing. In fact, only a small subset of malignant tumors has shown an objective response to these therapies. Development of resistance to anti-IGF-IR drugs may include upregulation of IR isoform A (IR-A) in cancer cells and its overactivation by increased secretion of autocrine IGF-II. These findings have led to the concept that co-targeting IR together with IGF-IR may increase therapy efficacy and prevent adaptive resistance to selective anti-IGF-IR drugs. IR blockade should be especially considered in tumors with high IR-A:IGF-IR ratio and high levels of autocrine IGF-II. Conversely, insulin sensitizers, which ameliorate insulin resistance associated with metabolic disorders and cancer treatments, may have important implications for cancer prevention and management. Only few drugs co-targeting the IR and IGF-IR are currently available. Ideally, future IR targeting strategies should be able to selectively inhibit the tumor promoting effects of IR without impairing its metabolic effects. PMID:22654833

  6. Antimicrobial therapy in neonatal intensive care unit.

    PubMed

    Tzialla, Chryssoula; Borghesi, Alessandro; Serra, Gregorio; Stronati, Mauro; Corsello, Giovanni

    2015-01-01

    Severe infections represent the main cause of neonatal mortality accounting for more than one million neonatal deaths worldwide every year. Antibiotics are the most commonly prescribed medications in neonatal intensive care units (NICUs) and in industrialized countries about 1% of neonates are exposed to antibiotic therapy. Sepsis has often nonspecific signs and symptoms and empiric antimicrobial therapy is promptly initiated in high risk of sepsis or symptomatic infants. However continued use of empiric broad-spectrum antibiotic treatment in the setting of negative cultures especially in preterm infants may not be harmless.The benefits of antibiotic therapy when indicated are clearly enormous, but the continued use of antibiotics without any microbiological justification is dangerous and only leads to adverse events. The purpose of this review is to highlight the inappropriate use of antibiotics in the NICUs, to exam the impact of antibiotic treatment in preterm infants with negative cultures and to summarize existing knowledge regarding the appropriate choice of antimicrobial agents and optimal duration of therapy in neonates with suspected or culture-proven sepsis in order to prevent serious consequences. PMID:25887621

  7. Fan-beam intensity modulated proton therapy

    PubMed Central

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-01-01

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  8. Fan-beam intensity modulated proton therapy

    SciTech Connect

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-11-15

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  9. An experimental study of pulsed micro-flows pertinent to continuous subcutaneous insulin infusion therapy

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2011-07-01

    An experimental study was conducted to investigate the unsteady micro-flow driven by an insulin pump commonly used in continuous subcutaneous insulin infusion (CSII) therapy. A microscopic particle image velocimetry (PIV) system was used to characterize the transient behavior of the micro-flow upon the pulsed excitation of the insulin pump in order to elucidate the underlying physics for a better understanding of the microphysical process associated with the insulin delivery in CSII therapy. The effects of air bubbles entrained inside the micro-sized CSII tubing system on the insulin delivery process were also assessed based on the micro-PIV measurements. While most solutions to insulin occlusion-related problems are currently based on clinical trials, the findings derived from the present study can be used to provide a better guidance for the troubleshooting of insulin occlusion in CSII therapy.

  10. How does blood glucose control with insulin save lives in intensive care?

    PubMed Central

    Van den Berghe, Greet

    2004-01-01

    Patients requiring prolonged intensive care are at high risk for multiple organ failure and death. Insulin resistance and hyperglycemia accompany critical illness, and the severity of this “diabetes of stress” reflects the risk of death. Recently it was shown that preventing hyperglycemia with insulin substantially improves outcome of critical illness. This article examines some potential mechanisms underlying prevention of glucose toxicity as well as the effects of insulin independent of glucose control. Unraveling the molecular mechanisms will provide new insights into the pathogenesis of multiple organ failure and open avenues for novel therapeutic strategies. PMID:15520847

  11. [Increasing cost of insulin therapy in Belgium. From a critical analysis of the situation to a search for practical solutions].

    PubMed

    Scheen, A J

    2006-09-01

    Cost related to insulin therapy is markedly increasing in Belgium, as in other Eucopean countries. In the present paper, we will briefly analyze the main reasons for such aa increase, integrate such observation withIn the global context of diabetes management and suggest some solutions to provide best care to insulin-treated diabetic patients at a reasonable cost. The rise of the cost of insulin therapy has a multifactorial origin. It mainly results from an increase in the number of diabetic patients, a more intensive management, In both type 1 and type 2 diabetes, and a greater use of more expansive insulin analogues. It is important to analyze the increase of the cost of insulin therapy within the global burden of diabetes melitus. Only a better responsibility of all health care partners, patients, physicians, pharmaceutical companies, public health authorities, could provide solutions allowing diabetic people to profit from best treatments they should receive in order to prevent diabetic complications, by far the main cause of expenses. PMID:17112161

  12. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile.

    PubMed

    Schwartz, Stanley S; Jellinger, Paul S; Herman, Mary E

    2016-08-01

    Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to

  13. A Survey of Insulin-Dependent Diabetes—Part I: Therapies and Devices

    PubMed Central

    Takahashi, Daisuke; Xiao, Yang; Hu, Fei; Lewis, Michael

    2008-01-01

    This paper surveys diabetes therapies from telemedicine viewpoint. In type 1 diabetes therapies, the exogenous insulin replacement is generally considered as a primary treatment. However, the complete replacement of exogenous insulin is still a challenging issue because of its complexity of modeling the dynamics, which is typically modeled nonlinearly. On the other hand, thanks to the progress of medical devices, currently the diabetes therapies are being automated. These medical devices include automated insulin pumps and blood glucose sensors. Insulin pumps are designed to create artificial insulin perfusion while they largely rely on the blood glucose profile measurements and these measurements are achieved by one or more blood glucose sensors. The blood glucose measurements are also important for the insulin-dependent diabetes therapies. An insulin pump along with sensors establishes a good feedback system providing the appropriate amount of the exogenous insulin on demand. Controlling the amount of exogenous insulin to suppress the blood glucose levels requires complicated computations. This paper mostly explains both type 1 and 2 diabetes and their mechanisms accompanied by descriptions of diabetes therapy and medical devices currently utilized in the therapy. PMID:18437199

  14. Performance of an Electronic Diary System for Intensive Insulin Management in Global Diabetes Clinical Trials

    PubMed Central

    Zhang, Shuyu; Mou, Jiani; Hackett, Andy P.; Raymond, Stephen A.; Chang, Annette M.

    2015-01-01

    Abstract Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient–investigator interactions during intensive insulin management in diabetes clinical trials. Materials and Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report. Results: Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively. Conclusions: The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins. PMID:25826466

  15. Single-energy intensity modulated proton therapy.

    PubMed

    Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

    2015-10-01

    In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT. PMID:26352616

  16. Single-energy intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Farace, Paolo; Righetto, Roberto; Cianchetti, Marco

    2015-09-01

    In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described. The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods. It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan. When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

  17. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

  18. Film Dosimetry for Intensity Modulated Radiation Therapy

    NASA Astrophysics Data System (ADS)

    Benites-Rengifo, J.; Martínez-Dávalos, A.; Celis, M.; Lárraga, J.

    2004-09-01

    Intensity Modulated Radiation Therapy (IMRT) is an oncology treatment technique that employs non-uniform beam intensities to deliver highly conformal radiation to the targets while minimizing doses to normal tissues and critical organs. A key element for a successful clinical implementation of IMRT is establishing a dosimetric verification process that can ensure that delivered doses are consistent with calculated ones for each patient. To this end we are developing a fast quality control procedure, based on film dosimetry techniques, to be applied to the 6 MV Novalis linear accelerator for IMRT of the Instituto Nacional de Neurología y Neurocirugía (INNN) in Mexico City. The procedure includes measurements of individual fluence maps for a limited number of fields and dose distributions in 3D using extended dose-range radiographic film. However, the film response to radiation might depend on depth, energy and field size, and therefore compromise the accuracy of measurements. In this work we present a study of the dependence of Kodak EDR2 film's response on the depth, field size and energy, compared with those of Kodak XV2 film. The first aim is to devise a fast and accurate method to determine the calibration curve of film (optical density vs. doses) commonly called a sensitometric curve. This was accomplished by using three types of irradiation techniques: Step-and-shoot, dynamic and static fields.

  19. Diabetes Patients' Experiences With the Implementation of Insulin Therapy and Their Perceptions of Computer-Assisted Self-Management Systems for Insulin Therapy

    PubMed Central

    Gude, Wouter T; Holleman, Frits; Hoekstra, Joost BL; Peek, Niels

    2014-01-01

    Background Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems. Objective Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients’ perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system. Methods In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd. Results When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression

  20. The Rationale for Insulin Therapy in Alzheimer's Disease.

    PubMed

    Ribarič, Samo

    2016-01-01

    Alzheimer's disease (AD) is the most common form of dementia, with a prevalence that increases with age. By 2050, the worldwide number of patients with AD is projected to reach more than 140 million. The prominent signs of AD are progressive memory loss, accompanied by a gradual decline in cognitive function and premature death. AD is the clinical manifestation of altered proteostasis. The initiating step of altered proteostasis in most AD patients is not known. The progression of AD is accelerated by several chronic disorders, among which the contribution of diabetes to AD is well understood at the cell biology level. The pathological mechanisms of AD and diabetes interact and tend to reinforce each other, thus accelerating cognitive impairment. At present, only symptomatic interventions are available for treating AD. To optimise symptomatic treatment, a personalised therapy approach has been suggested. Intranasal insulin administration seems to open the possibility for a safe, and at least in the short term, effective symptomatic intervention that delays loss of cognition in AD patients. This review summarizes the interactions of AD and diabetes from the cell biology to the patient level and the clinical results of intranasal insulin treatment of cognitive decline in AD. PMID:27240327

  1. Intensive therapy and autotransplantation in Hodgkin's disease.

    PubMed

    Reece, D E; Phillips, G L

    1994-09-01

    Intensive therapy and autologous marrow or peripheral blood stem cell transplantation is often utilized in Hodgkin's disease patients whose disease has progressed after primary conventional chemotherapy. A number of studies have described long-term disease-free survival in up to 50% of transplanted patients. High-dose chemotherapy conditioning regimens such as "CBV" or "BEAM" have been used more often than regimens containing total body irradiation. Usually unpurged autologous bone marrow has been utilized as the source of hematopoietic stem cell reconstitution, although recently the use of "primed" peripheral blood stem cells has increased markedly. The challenges of transplant-related toxicity and recurrence of disease post-transplant are discussed, as well as possible strategies to reduce these problems. The use of autologous transplantation is discussed in three clinical settings: patients who have failed to enter a complete remission (CR) after primary chemotherapy, those who have relapsed within 12 months of attaining a CR and those who have relapsed after a longer (i.e., > or = 12 months) first CR. When compared with conventional salvage chemotherapy, transplantation appears to produce a higher long-term disease-free survival rate in all of these patient groups. However, assessment of an advantage for autotransplantation, particularly in patients with long first remissions, is difficult without a Phase III trial. On the other hand, recently updated results from our center indicate that 72% of patients relapsing after long initial remissions benefit from autotransplantation at this point in their disease course, and that transplant-related mortality is low in this setting. Other issues addressed include the potential role of autologous transplantation as consolidation therapy in selected high-risk patients in an initial CR, as well as the utility of conventional chemotherapy and involved-field radiotherapy in conjunction with autotransplantation. PMID:7804123

  2. Insulin therapy refusal among type II diabetes mellitus patients in Kubang Pasu district, Kedah, Malaysia

    PubMed Central

    Tan, Wei Leong; Asahar, Siti Fairus; Harun, Noor Liani

    2015-01-01

    INTRODUCTION Diabetes mellitus is a rising non-communicable disease in Malaysia. Insulin therapy refusal is a challenge for healthcare providers, as it results in delayed insulin initiation. This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors. METHODS This cross-sectional study was conducted at seven public health clinics in Kubang Pasu district of Kedah, Malaysia, from March to October 2012. A newly developed and validated questionnaire was used and participants were selected via systematic random sampling. Only patients diagnosed with type II diabetes mellitus (T2DM) and under the public health clinic care in Kubang Pasu were included in the study. Multiple logistic regression was used to study the association between insulin therapy refusal and its associated factors. RESULTS There were 461 respondents and the response rate was 100%. Among these 461 patients with T2DM, 74.2% refused insulin therapy. The most common reason given for refusal was a lack of confidence in insulin injection (85.4%). Multiple logistic regression revealed that respondents who had secondary education were 55.0% less likely to refuse insulin therapy than those who had primary education or no formal education (adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25–0.82, p = 0.009). There was also a significant inverse association between glycated haemoglobin (HbA1c) level and insulin therapy refusal (adjusted OR 0.87, 95% CI 0.76–1.00, p = 0.047). CONCLUSION Insulin therapy refusal is common in Kubang Pasu. Educational status and HbA1c level should be taken into consideration when counselling patients on insulin therapy initiation. PMID:25532511

  3. Intranasal Insulin Therapy for Cognitive Impairment and Neurodegeneration: Current State of the Art

    PubMed Central

    de la Monte, Suzanne M.

    2015-01-01

    Introduction Growing evidence supports the concept that insulin resistance plays an important role in the pathogenesis of cognitive impairment and neurodegeneration, including in Alzheimer's disease (AD). The metabolic hypothesis has led to the development and utilization of insulin- and insulin agonist-based treatments. Therapeutic challenges faced include the ability to provide effective treatments that do not require repeated injections and also minimize potentially hazardous off-target effects. Areas covered This review covers the role of intra-nasal insulin therapy for cognitive impairment and neurodegeneration, particularly Alzheimer's disease. The literature reviewed focuses on data published within the past 5 years as this field is evolving rapidly. The author provides evidence that brain insulin resistance is an important and early abnormality in Alzheimer's disease, and that increasing brain supply and utilization of insulin improves cognition and memory. Emphasis was placed on discussing outcomes of clinical trials and interpreting discordant results to clarify the benefits and limitations of intranasal insulin therapy. Expert Opinion Intranasal insulin therapy can efficiently and directly target the brain to support energy metabolism, myelin maintenance, cell survival, and neuronal plasticity, which begin to fail in the early stages of neurodegeneration. Efforts must continue toward increasing the safety, efficacy, and specificity of intranasal insulin therapy. PMID:24215447

  4. Low intensity laser therapy: the clinical approach

    NASA Astrophysics Data System (ADS)

    Kahn, Fred

    2006-02-01

    Recently, there has been significant improvement in the process of research and application of Low Intensity Laser Therapy (LILT). Despite this positive direction, a wide discrepancy between the research component and clinical understanding of the technology remains. In our efforts to achieve better clinical results and more fully comprehend the mechanisms of interaction between light and cells, further studies are required. The clinical results presented in this paper are extrapolated from a wide range of musculoskeletal problems including degenerative osteoarthritis, repetitive motion injuries, sports injuries, etc. The paper includes three separate clinical studies comprising 151, 286 and 576 consecutive patient discharges at our clinic. Each patient studied received a specific course of treatment that was designed for that individual and was modified on a continuing basis as the healing process advanced. On each visit, clinical status correlation with the duration, dosage and other parameters was carried out. The essentials of the treatment consisted of a three stage approach. This involved a photon stream emanating from a number of specified gallium-aluminum-arsenide diodes; stage one, red light array, stage two consisting of an array of infrared diodes and stage three consisting of the application of an infrared laser diode probe. On average, each of these groups required less than 10 treatments per patient and resulted in a significant improvement / cure rate greater than 90% in all conditions treated. This report clearly demonstrates the benefits of LILT, indicating that it should be more widely adapted in all medical therapeutic settings.

  5. High intensity interval training improves liver and adipose tissue insulin sensitivity

    PubMed Central

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  6. Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

    PubMed Central

    Feher, Michael D; Brazier, John; Schaper, Nicolaas; Vega-Hernandez, Gabriela; Bøgelund, Mette

    2016-01-01

    Objectives This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes. Research design and methods Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment. Results A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1%-point decrease in HbA1c; US$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events. Conclusions Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important. PMID:27158518

  7. Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy.

    PubMed

    Shimoda, Seiya; Okubo, Mina; Koga, Kotaro; Sekigami, Taiji; Kawashima, Junji; Kukidome, Daisuke; Igata, Motoyuki; Ishii, Norio; Shimakawa, Akiko; Matsumura, Takeshi; Motoshima, Hiroyuki; Furukawa, Noboru; Nishida, Kenro; Araki, Eiichi

    2015-01-01

    To assess the total daily inulin dose (TDD) and contribution of basal insulin to TDD and to identify the predictive factors for insulin requirement profiles in subjects with type 2 diabetes, we retrospectively examined insulin requirement profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy (BBT) (mean age, 60.1 ± 12.9 years; HbA1c, 10.2 ± 4.5%). Target plasma glucose level was set between 80 and 129 mg/dL before breakfast and between 80 and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also analyzed the relationship between the insulin requirement profiles (TDD and basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical parameters. The mean TDD was 0.463 ± 0.190 unit/kg/day (range, 0.16-1.13 unit/kg/day). The mean B/TD ratio was 0.300 ± 0.099 (range, 0.091-0.667). A positive correlation of TDD with B/TD ratio was revealed by linear regression analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post-breakfast glucose levels before titrating insulin as an independent determinant of the insulin requirement profile [Std β (standard regression coefficient) = 0.228, p<0.01 for TDD, Std β = -0.189, p<0.01 for B/TD ratio]. The TDD was <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects in the present study. These findings may have relevance in improving glycemic control and decreasing the risk of hypoglycemia and weight gain in subjects with type 2 diabetes treated with BBT. PMID:25392020

  8. Effectiveness and tolerability of treatment intensification to basal–bolus therapy in patients with type 2 diabetes on previous basal insulin-supported oral therapy with insulin glargine or supplementary insulin therapy with insulin glulisine: the PARTNER observational study

    PubMed Central

    Pfohl, Martin; Siegmund, Thorsten; Pscherer, Stefan; Pegelow, Katrin; Seufert, Jochen

    2015-01-01

    Background Due to the progressive nature of type 2 diabetes mellitus (T2DM), antidiabetic treatment needs to be continuously intensified to avoid long-term complications. In T2DM patients on either basal insulin-supported oral therapy (BOT) or supplementary insulin therapy (SIT) presenting with HbA1c values above individual targets for 3–6 months, therapy should be intensified. This study investigated effectiveness and tolerability of an intensification of BOT or SIT to a basal–bolus therapy (BBT) regimen in T2DM patients in daily clinical practice. Methods This noninterventional, 8-month, prospective, multicenter study evaluated parameters of glucose control, occurrence of adverse events (eg, hypoglycemia), and acceptance of devices in daily clinical practice routine after 12 and 24 weeks of intensifying insulin therapy to a BBT regimen starting from either preexisting BOT with insulin glargine (pre-BOT) or preexisting SIT with ≥3 daily injections of insulin glulisine (pre-SIT). Results A total of 1,530 patients were documented in 258 German medical practices. A total of 1,301 patients were included in the full analysis set (55% male, 45% female; age median 64 years; body mass index median 30.8 kg/m2; pre-BOT: n=1,072; pre-SIT: n=229), and 1,515 patients were evaluated for safety. After 12 weeks, HbA1c decreased versus baseline (pre-BOT 8.67%; pre-SIT 8.46%) to 7.73% and 7.66%, respectively (Δ mean −0.94% and −0.80%; P<0.0001). At week 24, HbA1c was further reduced to 7.38% and 7.30%, respectively (Δ mean −1.29% and −1.15%; P<0.0001), with a mean reduction of fasting blood glucose values in both treatment groups by more than 46 mg/dL. An HbA1c goal of ≤6.5% was reached by 17.9% (pre-BOT) and 18.6% (pre-SIT), and an HbA1c ≤7.0% by 46.1% (pre-BOT) and 43.0% (pre-SIT) of patients. During 24 weeks, severe as well as serious hypoglycemic events were rare (pre-BOT: n=5; pre-SIT: n=2; pretreated with both insulins: n=1). Conclusion Intensifying

  9. Intensity-Modulated Radiation Therapy (IMRT)

    MedlinePlus

    ... modulating—or controlling—the intensity of the radiation beam in multiple small volumes. IMRT also allows higher ... of multiple intensity-modulated fields coming from different beam directions produce a custom tailored radiation dose that ...

  10. Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients☆

    PubMed Central

    Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  11. Impact of clinical pharmacist collaboration in patients beginning insulin pump therapy: a retrospective and cross-sectional analysis*

    PubMed Central

    Ledford, James L.; Hess, Rick; Johnson, Frank P.

    2013-01-01

    Objective To measure clinical and qualitative outcomes in patients with diabetes mellitus transitioning from intensive insulin therapy using multiple daily injections (MDI) to continuous subcutaneous insulin infusion (CSII) initiated and managed by clinical pharmacists under a collaborative practice agreement in a primary care setting without an endocrinologist. Research design and methods This study was a retrospective and cross-sectional analysis of data from an electronic medical record (EMR) and patient survey at a large primary care private practice. Patients with type 1 or type 2 diabetes who were ≥18 years old, started on CSII between 2007 and 2010, and had at least one follow-up visit post-CSII were analyzed. Mean HbA1c results were stratified across 3-month intervals post-CSII initiation and compared to pre-CSII levels. Body mass index (BMI), the number of diabetes-related clinic visits with the primary care physician (PCP), and non-insulin diabetes medication use was compared pre- and post-CSII initiation. Paper-based questionnaires were used to assess patient satisfaction with CSII vs MDI and pharmacist-led services. Results Twenty-five patients were included in the analysis. HbA1c decreased from 8.69 to 7.52% pre and post-CSII, respectively (p < 0.001). HbA1c also decreased across all 3-month intervals post-CSII. BMI decreased from 33.0 to 32.3 kg/m2 pre- and post-CSII, respectively (p = 0.085). Fewer diabetes-related PCP visits were completed post-CSII (5.09 vs 3.78 visits/year, p = 0.009), and less non-insulin diabetes medications were prescribed post-CSII (p < 0.001). Patients felt more comfortable controlling glycemic excursions and resultant insulin adjustments with CSII compared to MDI (p < 0.001). Conclusions Pharmacist-led CSII services appear to improve diabetes control in patients requiring intensive insulin therapy. Patients report greater comfort using CSII and strong confidence in the abilities of the pharmacist

  12. Identifying and meeting the challenges of insulin therapy in type 2 diabetes

    PubMed Central

    Sorli, Christopher; Heile, Michael K

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic illness that requires clinical recognition and treatment of the dual pathophysiologic entities of altered glycemic control and insulin resistance to reduce the risk of long-term micro- and macrovascular complications. Although insulin is one of the most effective and widely used therapeutic options in the management of diabetes, it is used by less than one-half of patients for whom it is recommended. Clinician-, patient-, and health care system-related challenges present numerous obstacles to insulin use in T2DM. Clinicians must remain informed about new insulin products, emerging technologies, and treatment options that have the potential to improve adherence to insulin therapy while optimizing glycemic control and mitigating the risks of therapy. Patient-related challenges may be overcome by actively listening to the patient’s fears and concerns regarding insulin therapy and by educating patients about the importance, rationale, and evolving role of insulin in individualized self-treatment regimens. Enlisting the services of Certified Diabetes Educators and office personnel can help in addressing patient-related challenges. Self-management of diabetes requires improved patient awareness regarding the importance of lifestyle modifications, self-monitoring, and/or continuous glucose monitoring, improved methods of insulin delivery (eg, insulin pens), and the enhanced convenience and safety provided by insulin analogs. Health care system-related challenges may be improved through control of the rising cost of insulin therapy while making it available to patients. To increase the success rate of treatment of T2DM, the 2012 position statement from the American Diabetes Association and the European Association for the Study of Diabetes focused on individualized patient care and provided clinicians with general treatment goals, implementation strategies, and tools to evaluate the quality of care. PMID:25061317

  13. Insulin

    MedlinePlus

    ... pump is connected to your body by a flexible tube that has a tip that sticks under your skin. A cartridge of insulin is put in the pump. The insulin flows through the tube into your body. The pump controls how much insulin goes into your body. The ...

  14. Intensive Diabetes Therapy and Ocular Surgery in Type 1 Diabetes

    PubMed Central

    2015-01-01

    BACKGROUND The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes. METHODS Between 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies. RESULTS Over a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P = 0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P = 0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P = 0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up. CONCLUSIONS

  15. [Diet therapy in non-insulin dependent diabetes mellitus (NIDDM)].

    PubMed

    Cavallo-Perin, P; Bodoni, P; Marena, S

    1997-12-01

    The main approach in NIDDM therapy is diet. Most patients present insulin resistance characterized by overweight, VLDL increase, minimal increase of LDL, decrease of HDL cholesterol, and hypertension. The overall goals of nutrition therapy are the maintenance of near normal glucose levels, and the achievement of optimal serum lipid levels with adequate calories for maintaining or attaining a reasonable body weight. In presence of obesity and hypertension even a slightly weight loss could achieve an improvement in metabolic control and in hypertension with a better life expectance. General-ly carbohydrate intake would represent the 50-60% of total caloric amount (with preference to those with low glycemic index), and lipids no more than 35% (less than 10% of these 10-15% from monounsaturated fats with less than 300 mg/day of cholesterol). If elevated very low density lipoproteins level is the primary problem, a beneficial approach is 10% of total caloric intake from saturated fats, 10% from polyunsaturated, and 15-20% from monounsaturated fats with less than 200 mg/day of cholesterol and 40% of carbohydrates. A large amount of fructose (20% of calories) may increase LDL levels but sweeteners as saccarine or aspartame are approved and determine a better diet compliance. Daily consumpion of 20-35 g of dietary fibres from food sources is recommended for metabolic control. Protein intake would be of about 10% of total caloric amount especially in presence of diabetic nepropathy. Alcohol would not exceed 30 g/day for men and 20 g/day for women keeping in mild that alcohol may worsen metabolic control, diet compliance, and may be dangerous itself. For people with hypertension a decrease of dietary sodium intake is recommended. Nutritional recommendations are developed to meet treatment goals and desired outcomes. Monitoring metabolic parameters, blood pressure, and body weight is very important to ensure successful outcomes. PMID:16501444

  16. Robust optimization of intensity modulated proton therapy

    SciTech Connect

    Liu Wei; Zhang Xiaodong; Li Yupeng; Mohan, Radhe

    2012-02-15

    Purpose: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. Methods: The authors use the so-called ''worst-case robust optimization'' to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed--one each for {+-} setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for {+-} range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. Results: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the

  17. Targeting insulin-producing beta cells for regenerative therapy.

    PubMed

    Migliorini, Adriana; Roscioni, Sara S; Lickert, Heiko

    2016-09-01

    Pancreatic beta cells differ in terms of glucose responsiveness, insulin secretion and proliferative capacity; however, the molecular pathways that regulate this cellular heterogeneity are unknown. We have identified the Wnt-planar cell polarity (PCP) effector Flattop (FLTP) as a biomarker that identifies mature beta cells in the islets of Langerhans. Interestingly, three-dimensional architecture and Wnt-PCP ligands are sufficient to trigger mouse and human beta cell maturation. These results highlight the fact that novel biomarkers shed light on the long-standing mystery of beta cell heterogeneity and identify the Wnt-PCP pathway as triggering beta cell maturation. Understanding heterogeneity in the islets of Langerhans might allow targeting of beta cell subpopulations for regenerative therapy and provide building principles for stem cell-derived islets. This review summarises a presentation given at the 'Can we make a better beta cell?' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Amin Ardestani and Kathrin Maedler, DOI: 10.1007/s00125-016-3892-9 , and by Harry Heimberg and colleagues, DOI: 10.1007/s00125-016-3879-6 ) and a commentary by the Session Chair, Shanta Persaud (DOI: 10.1007/s00125-016-3870-2 ). PMID:27412250

  18. Linagliptin as add-on therapy to insulin for patients with type 2 diabetes

    PubMed Central

    von Websky, Karoline; Reichetzeder, Christoph; Hocher, Berthold

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a highly prevalent, progressive disease that often is poorly controlled. The combination of an incretin-based therapy and insulin is a promising approach to optimize the management of glycemic control without hypoglycemia and weight gain. Linagliptin, a recently approved oral dipeptidyl peptidase-4 inhibitor, has a unique pharmacological profile. The convenient, once-daily dosing does not need adjustment in patients with hepatic and/or renal impairment. In clinical studies linagliptin shows an important reduction of blood glucose with an overall safety profile similar to that of placebo. So far, the combination of linagliptin and insulin has been tested in three major clinical studies in different populations. It has been shown that linagliptin is an effective and safe add-on therapy to insulin in patients with T2DM. The efficacy and safety of this combination was also shown in vulnerable, elderly T2DM patients and in patients with T2DM and renal impairment. Favorable effects regarding the counteraction of hypoglycemia make linagliptin especially interesting as an add-on therapy to insulin. This review aims to present the existing clinical studies on the efficacy and safety of linagliptin as add-on therapy to insulin in patients with T2DM in the context of current literature. Additionally, the possible advantages of linagliptin as an add-on therapy to insulin in relation to cardiovascular safety, patient-centered therapy and the prevention of hypoglycemia, are discussed. PMID:24204157

  19. The nuts and bolts of subcutaneous insulin therapy in non-critical care hospital settings.

    PubMed

    Juneja, Rattan; Foster, Shonda A; Whiteman, Douglas; Fahrbach, Jessie L

    2010-01-01

    In non-critical care settings, patients with hyperglycemia experience increased morbidity and mortality. Despite an increased recognition of the importance of treating inpatient hyperglycemia, many patients are still not adequately controlled. Insulin offers flexibility to address varying glucose levels and therefore is the preferred therapy to achieve recommended targets and manage hyperglycemia. Traditional sliding-scale insulin regimens often ineffectively control blood glucose levels as they are unable to mimic physiologic insulin secretion. Basal-bolus insulin regimens are recognized as a more effective way to correct hyperglycemia in non-critical care settings and a systematic glycemic control program is necessary to address hyperglycemia while minimizing hypoglycemia. Critical components of these programs include addressing barriers to glycemic control, understanding varying needs of different types of patients, and developing standardized subcutaneous insulin orders to achieve target glucose levels. This article provides strategies for using insulin in non-critical care settings to facilitate glycemic control. PMID:20107299

  20. [Insulin therapy in type 2 diabetes: a review of "when" over "how" up to "why"].

    PubMed

    Laimer, Markus; Jenni, Stefan; Stettler, Christoph

    2015-02-11

    Type 2 Diabetes is characterized by its progressive character. An intensification of the therapy is necessary in most cases over the years and insulin is typically used as an add-on agent when oral antidiabetic regimes are judged to be no longer sufficient. However, insulin can also be used in the initial phase of the disease directly after diagnosis of diabetes. Intermittent worsening of glycemic control (e.g. due to infectious diseases or corticosteroids) may be additional indications for an insulin treatment at an earlier stage. Noticeably, insulin can often be stopped if the triggering event or treatment is reversible, thereby countering the widely spread fear of dependency on insulin. We recommend a rather cautious starting dose of insulin and individual adaptations thereafter. Well-informed patients can also perform such adaptations themselves. PMID:25669222

  1. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    PubMed

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. PMID:26450442

  2. Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review

    PubMed Central

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

  3. Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review.

    PubMed

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3-5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

  4. Insulin Absorption from Lipodystrophic Areas: A (Neglected) Source of Trouble for Insulin Therapy?

    PubMed Central

    Heinemann, Lutz

    2010-01-01

    The experienced clinical diabetologist first checks the skin at the area where the patient usually injects his insulin when he sees widely fluctuating blood glucose levels in the diary of the patient. He knows that insulin absorption from skin with lipodystrophic changes is irregular. However, our scientific knowledge about why this is the case is very limited. Most probably, the number of blood vessels near the insulin depot in the subcutaneous tissue varies depending on the nature of the lipodystrophic changes, or the structural changes in this tissue hamper the diffusion of insulin. Not only is our knowledge about the number of patients who exhibit such changes very limited, but also our understanding why such changes show up in certain patients and not in others is minimal. More practically important, we also have few quantitative studies investigating the impact of this diabetes-related complication on insulin absorption/insulin action; however, it is not difficult to run such studies in practice. Nevertheless, it is impressive to see how often metabolic control improves considerably once the patients apply the insulin into other skin areas. PMID:20513344

  5. Effect of Insulin Sensitizer Therapy on Amino Acids and their Metabolites

    PubMed Central

    Irving, B.A.; Carter, R.E.; Soop, M.; Weymiller, A.; Syed, H.; Karakelides, H.; Bhagra, S.; Short, K.R.; Tatpati, L.; Barazzoni, R.; Nair, K.S.

    2015-01-01

    Aims Prior studies have reported that elevated concentrations of several plasma amino acids (AA) in plasma, particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. Methods We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI~30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Results Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Conclusions Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. PMID:25733201

  6. Continuous subcutaneous IGF-1 therapy via insulin pump in a patient with Donohue syndrome

    PubMed Central

    Weber, David R.; Stanescu, Diana E.; Semple, Robert; Holland, Cheryl; Magge, Sheela N.

    2015-01-01

    Donohue syndrome (DS) is a severe form of congenital insulin resistance due to mutation(s) in the insulin receptor (INSR) gene. Given the similarities between insulin and insulin-like growth factor 1 (IGF-1) receptors, recombinant human IGF-1 (rhIGF-1) has been used to treat severe insulin resistance due to INSR mutation(s). Traditional subcutaneous therapy may be limited by the shortened IGF-1 half-life in these patients. We report the case of a female with molecularly confirmed DS treated with continuous rhIGF-1 therapy via an insulin pump. With treatment, the patient’s hemoglobin A1c decreased from 9.8% to 8.8%, and her weight increased by 0.8 kg. Development of an ovarian tumor complicated her course, but it was unclear whether this was related to rhIGF-1 therapy. Limited treatment options exist for patients with DS. The use of continuous rhIGF-1 via an insulin pump may be a viable option, although further experience is needed to establish safety and efficacy. PMID:25153212

  7. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  8. Treating Hyperglycemia and Diabetes With Insulin Therapy: Transition From Inpatient to Outpatient Care

    PubMed Central

    Lavernia, Frank

    2008-01-01

    Abstract and Introduction Abstract Context Intensive insulin therapy is recommended to control glucose elevations in the critically ill and has been shown to significantly improve outcomes among hospital inpatients with acute hyperglycemia or newly diagnosed diabetes. Once discharged, the hyperglycemic patient may require ongoing outpatient care, most often under the attention of a primary care physician. Evidence acquisition The purpose of this review is to provide a background of in-hospital hyperglycemia management and discharge planning in preparation for continued outpatient care. Primary data sources were identified through a PubMed search (1990–2007) using keywords, such as diabetes, hyperglycemia, in-hospital, discharge, and insulin. Evidence synthesis Hyperglycemia protocols with strict glycemic goals have been shown to improve morbidity and mortality among critically ill inpatients. Discharge planning should prepare patients for self-care and give them the survival skills necessary to maintain glycemic control. In preparation for discharge, patients are usually transitioned from insulin infusions to subcutaneous insulin administered through an appropriate basal-prandial regimen. Conclusion A thorough understanding of hyperglycemia history and treatment will allow the primary care physician to deliver optimal diabetes care and thereby improve both short-term and long-term outcomes for those patients with critical illnesses and hyperglycemia or diabetes. Introduction Hyperglycemia, when left untreated, can have a negative impact on the patient's prognosis and outcome during the hospital stay and after discharge.[1–5] The prevalence of hyperglycemia in hospitalized patients is high, and may be associated with multiple factors: First, about 20.8 million Americans have diabetes, 6.2 million of whom (around one third) have not been diagnosed.[1,6] Furthermore, diabetes itself may contribute to hospitalization because it can lead to cardiovascular disease

  9. Effect of metformin therapy on 2-h post-glucose insulin levels in patients of polycystic ovarian syndrome

    PubMed Central

    Saxena, Pikee; Prakash, Anupam; Nigam, Aruna

    2010-01-01

    AIMS: To evaluate if 2-h post glucose insulin level is an effective tool to monitor insulin resistance in response to metformin therapy, in infertile women with polycystic ovarian syndrome (PCOS). SETTINGS AND DESIGN: This prospective observational study was carried out in a tertiary care infertility clinic. MATERIALS AND METHODS: 40 women with PCOS were categorized as having insulin resistance if fasting or 2-h post glucose insulin levels were >25 or >41μU/ml respectively. Post glucose insulin was compared before and after six months of metformin therapy along with other clinical, hormonal and metabolic parameters by using McNemar and the Student’s t-test. RESULTS: Fasting insulin was elevated in 4 (10%) and post-load insulin in 34 (85%) patients; after metformin therapy respective values were 2 (5%) and 16 (40%). Metformin therapy reduced post glucose insulin levels (P<0.001), improved the regularity of periods (P<0.001) and resulted in reduction of LH levels (P<0.001), total testosterone (P<0.001) and mean Body mass index (BMI) (P=0.047). Metformin therapy did not alter waist-hip ratio and fasting insulin levels. CONCLUSION: 2-h post glucose insulin level is an effective tool to monitor insulin resistance in PCOS patients and improves significantly after metformin therapy, similar to improvements observed in clinical, hormonal and metabolic parameters. PMID:21234175

  10. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  11. [Overprotectiveness as a coping reaction in intensive physical therapy].

    PubMed

    Sarimski, K; Hoffmann, I W

    1993-06-01

    25 mothers of children with cerebral palsy who were doing daily intensive physical therapy (Vojta) completed questionnaires concerning their child's temperament, parental attitudes and how they coped with everyday problems. Their responses were compared to those given by mothers who were not under the stress of conducting therapy. The results revealed compensatory coping processes: Mothers doing therapy try to compensate for their child's stress by being overprotective in ambiguous everyday situations. PMID:8342332

  12. NOCTURNAL HYPOGLYCEMIA--THE MAIN INDICATION FOR INSULIN PUMP THERAPY IN ADULTHOOD.

    PubMed

    Baretić, Maja; Kraljević, Ivana; Renar, Ivana Pavlić

    2016-03-01

    The aim was to determine which adult type 1 diabetic patient receiving multiple daily injection therapy is the most appropriate candidate for insulin pump therapy, while taking into consideration limited insulin pump affordability in Croatia. A total of 145 type 1 diabetic patients (52% diagnosed in adult age) were monitored at the Department of Endocrinology, Clinical Department of Internal Medicine, Zagreb University Hospital Center from 2009 to 2014. Twenty-one patients started insulin pump therapy in adulthood (seven men and 14 women, median age 27). Five patients had chronic complications (retinopathy in two, polyneuropathy in one, and both nephropathy and retinopathy in two patients). The median HbA1c at the initiation of pump therapy was 6.95% versus 6.5% after 1 year of pump therapy. Patients were stratified according to indications for insulin pump therapy (frequent and/or severe hypoglycemia, specific lifestyle, having not reached glycemic goals despite adherence/labile diabetes, and preconception). Patients could meet more than one criterion. Initially, the occurrence of hypoglycemia was analyzed by 6-day continuous glucose monitoring, while re-evaluation was done after collecting history data at 1 year ± 3 months. Initially, all patients had a median of 5 hypoglycemias/6 days (30% nocturnal) versus 1 hypoglycemia/6 days (without nocturnal) after 1 year. The Wilcoxon signed-rank test yielded a statistically significant difference in hypoglycemic events, nocturnal hypoglycemia and HbA1c. Patients commencing insulin pump therapy due to hypoglycemia initially had median HbA1c of 6.7% with 7 hypoglycemia/6 days (50% nocturnal). After one year, median HbA1c was 6% with 1 hypoglycemia/6 days (without nocturnal). In conclusion, the main indication for insulin pump therapy in adults is the frequency of hypoglycemia, especially nocturnal ones. PMID:27333724

  13. Intense Pulsed Light Therapy for Skin Rejuvenation.

    PubMed

    DiBernardo, Barry E; Pozner, Jason N

    2016-07-01

    Intense pulsed light (IPL), also known as pulsed light and broad band light, is a nonlaser light source used to treat a variety of vascular and pigmented lesions, photo damage, active acne, and unwanted hair. Current IPL systems are much improved from older-generation devices with better calibration, integrated cooling, and improved tuning. These devices are extremely popular because of their versatility and are often the first devices recommended and purchased in many offices. PMID:27363767

  14. (Poly)peptide-based therapy for diabetes mellitus: insulins versus incretins.

    PubMed

    Bavec, Aljoša

    2014-03-18

    Insulin therapy remains the standard of care for achieving and maintaining adequate glycemic control, especially in hospitalized patients with critical and noncritical illnesses. Insulin therapy is more effective against elevated fasting glycaemia but less in the reduction of postprandial hyperglycaemia. It is associated with a high incidence of hypoglycemia and weight gain. Contrary, GLP-1 mimetic therapy improves postprandial glycaemia without the hypoglycaemia and weight gain associated with aggressive insulin therapy. Moreover, it has the potential to reduce cardiovascular related morbidity. However, its increased immunogenicity and severe gastrointestinal adverse effects present a huge burden on patients. Thus, a right combination of basal insulin which has lowering effect on fasting plasma glucose and GLP-1 mimetic with its lowering effect on postprandial plasma glucose with minimal gastrointestinal adverse effects, seems the right therapy choice from a clinical point of view for some diabetic patients. In this article, we discuss the pros and cons of the use of insulin analogues and GLP-1 mimetics that are associated with the treatment of type 2 diabetes. PMID:24412390

  15. A REVIEW OF LOW-INTENSITY ULTRASOUND FOR CANCER THERAPY

    PubMed Central

    WOOD, ANDREW K. W.; SEHGAL, CHANDRA M.

    2015-01-01

    The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients. PMID:25728459

  16. Respiratory syncytial virus, infants and intensive therapy.

    PubMed

    Bueno, Ieda Aparecida Correa; Riccetto, Adriana Gut Lopes; Morcillo, André Moreno; Arns, Clarice Weis; Baracat, Emílio Carlos Elias

    2012-01-01

    The aims of this study were to determine the presence of respiratory syncytial virus (RSV) and to assess the clinical features of the disease in infants with acute low respiratory tract infection hospitalized at pediatric intensive care units (PICU) of two university teaching hospitals in São Paulo State, Brazil. Nasopharyngeal secretions were tested for the RSV by the polymerase chain reaction. Positive and negative groups for the virus were compared in terms of evolution under intensive care (mechanical pulmonary ventilation, medications, invasive procedures, complications and case fatality). Statistical analysis was performed using the Mann Whitney and Fisher's exact tests. A total of 21 infants were assessed, 8 (38.1%) of whom were positive for RSV. The majority of patients were previously healthy while 85.7% required mechanical pulmonary ventilation, 20/21 patients presented with at least one complication, and the fatality rate was 14.3%. RSV positive and negative groups did not differ for the variables studied. Patients involved in this study were critically ill and needed multiple PICU resources, independently of the presence of RSV. Further studies involving larger cohorts are needed to assess the magnitude of the impact of RSV on the clinical evolution of infants admitted to the PICU in our settings. PMID:22358363

  17. Impact of patient attitudes and beliefs to insulin therapy upon initiation, and their attitudinal changes after initiation: the DAWN Japan study.

    PubMed

    Odawara, Masato; Ishii, Hitoshi; Tajima, Naoko; Iwamoto, Yasuhiko

    2016-01-01

    Objective As a part of the Diabetes Attitudes, Wishes and Needs (DAWN) Japan study, a multi-center, questionnaire-based survey conducted between 2004 and 2005, this analysis aimed to (1) explore patients' attitudes and beliefs contributing to their decision to start insulin therapy, and (2) assess the changes in their attitudes and beliefs after actual initiation. Methods Insulin-naive patients with type 2 diabetes who were recommended to start insulin therapy (n = 149) were invited to answer a 21-item questionnaire consisting of five clusters assessing their attitudes and beliefs toward insulin therapy. The questionnaire was administered twice: first upon insulin recommendation, and then 1 month after insulin initiation for those who started and 4 months after for those who did not. Results Of 130 patients included in the analysis, 74 patients (56.9%) started insulin therapy. 'Negative image of injections' and 'Positive image toward insulin therapy' were significantly associated with patient decision to start insulin therapy (odds ratios [95% CI]: 0.49 [0.32-0.76] and 2.58 [1.51-4.42], respectively). After insulin initiation, 'Negative image of injections', 'Positive image toward insulin therapy', 'Feelings of guilt regarding diabetes self-management', and 'Negative image toward insulin therapy' decreased significantly (P < 0.001 for all). 'Social/interpersonal effects' did not change after insulin initiation. Conclusions This study demonstrated that patients who started insulin therapy were less likely to have negative images of injections and more likely to have positive images toward insulin therapy. Starting insulin therapy did not deteriorate the patient's overall impression of therapy. The key limitation is the relatively small sample size (n = 130). The results suggest that education about the benefits of insulin therapy may help patients who are not ready to initiate insulin overcome their barrier to early insulin initiation and practical

  18. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

  19. Carbohydrate-to-Insulin Ratio in a Mediterranean Population of Type 1 Diabetic Patients on Continuous Subcutaneous Insulin Infusion Therapy

    PubMed Central

    Alcántara-Aragón, Valeria; Gonzalez, Cintia; Corcoy, Rosa; Ubeda, Justa; Chico, Ana

    2014-01-01

    Background: The carbohydrate-to-insulin ratio (CIR) is initially calculated from the total daily insulin dose (TDID). However, CIR likely presents variations owing to different population characteristics and intraday variations not being taken into account by most formulas. No information is available concerning the Mediterranean population. We investigated the CIR used by patients with type 1 diabetes (T1DM) using continuous subcutaneous insulin infusion (CSII) therapy in a Mediterranean area, to identify possible intraday variations and establish an adequate formula to calculate CIR. Methods: Data from 170 T1DM patients from Barcelona were obtained retrospectively from the Spanish National Registry of CSII Therapy (SNR-CSII). Theoretical CIR was calculated using the formula: 500 divided by TDID. This theoretical CIR was compared to the real CIR. Results: The real CIR was also compared between main meals. Patients with HbA1c < 7% (n = 44) were considered a reference group for accurate bolus calculation and were analyzed as a subgroup. The real CIR used was 11.5 g/UI for breakfast, 12 g/UI for lunch, and 13.3 g/UI for dinner. CIR obtained by the 500/TDID formula for all meals was 15.5 g/UI. We obtained similar results for the group with HbA1c < 7%. The real CIR differed significantly from the theoretical CIR values and between breakfast and the other main meals (P < .005). Conclusions: CIR in our population was significantly lower for breakfast than for other meals. CIR using the 500/TDID formula underestimated prandial insulin requirements. A calculation of 350/TDID for breakfast and 400/TDID for lunch and dinner would be more appropriate for this population. PMID:25519294

  20. Update on a Quality Initiative to Standardize Perioperative Care for Continuous Subcutaneous Insulin Infusion Therapy

    PubMed Central

    Mackey, Patricia A.; Thompson, Bithika M.; Boyle, Mary E.; Apsey, Heidi A.; Seifert, Karen M.; Schlinkert, Richard T.; Stearns, Joshua D.; Cook, Curtiss B.

    2015-01-01

    Objective: The objective of the analysis was to review the effectiveness of a care process model (CPM) developed to guide management of patients on insulin pump therapy undergoing elective surgical procedures. Methods: Electronic medical records were reviewed to assess the impact of the CPM on documentation of insulin pump status, glucose monitoring, and safety during the perioperative phase of care. Post-CPM care was compared with management provided before CPM implementation. Results: We reviewed 45 cases on insulin pump therapy in the pre-CPM cohort and 106 in the post-CPM cohort. Demographic characteristics, categories of surgery, and perioperative times were not significantly different between the 2 groups. Recommended hemoglobin A1c monitoring occurred in 73% of cases in the pre-CPM cohort but improved to 94% in the post-CPM group (P < .01). There was a higher frequency of documentation of the insulin pump during the preoperative, intraoperative, and postanesthesia care unit segments of care in the post- vs pre-CPM periods (all P < .01). The number of cases with intraoperative glucose monitoring increased (57% pre-CPM vs 81% post-CPM; P < .01). Glycemic control was comparable between the 2 CPM periods. Hypoglycemia was rare, with only 3 episodes in the pre-CPM group and 4 in the post-CPM. No adverse events associated with perioperative insulin pump use were observed. Conclusions: This analysis adds to previous data on use of insulin pump therapy during the perioperative period. Some processes require additional attention, but data continue to indicate that a standardized approach to care can lead to a successful and safe transition of insulin pump therapy throughout the perioperative period. PMID:26092687

  1. Exploring patients’ perceptions for insulin therapy in type 2 diabetes: a Brazilian and Canadian qualitative study

    PubMed Central

    Guimarães, Camila; Marra, Carlo A; Gill, Sabrina; Meneilly, Graydon; Simpson, Scot; Godoy, Ana LPC; Foss de, Maria Cristina; Freitas; Queiroz, Regina HC; Lynd, Larry

    2010-01-01

    Objective: To explore which attributes of insulin therapy drive patients’ preferences for management in Canada and Brazil. Methods: A qualitative design was implemented in which a total of 32 patients with type 2 diabetes from Canada and Brazil, were interviewed in one of the 4 focus groups, or 16 individual interviews. Eighteen participants (56%) were women and fourteen participants (44%) were men (15 insulin nonusers and 17 insulin users). Two focus groups of 4 participants each and 9 individual interviews were conducted in Brazil. In Canada, 2 focus groups of 4 participants each and 7 individual interviews were conducted. A framework analysis was used to analyse all data. Results: Brazilian participants, when considering two insulin treatments, would prefer the one that had fewer side-effects (specially hypoglycemia events), was noninjectable, had the lowest cost and was most effective. Meanwhile, Canadian participants would prefer a treatment that had fewer side-effects (specially weight gain), was less invasive, was more convenient and was most effective. Conclusions: Finding the insulin-delivery system and the attributes of insulin therapy that best meet patients’ preferences may lead to improved control, through improved compliance, which may ultimately reduce the financial burden of the disease and improve quality of life. PMID:20694179

  2. [Advantages and disadvantages of insulin therapy in elderly diabetics with asymptomatic hyperglycemia].

    PubMed

    Straumann, M; Staffelbach, O; Sonnenberg, G E; Keller, U; Berger, W

    1979-12-01

    15 elderly diabetic patients with fasting blood glucose levels above 160 mg/100 ml, without hyperglycemic symptoms and previously treated with oral antidiabetic agents, were put on insulin. The change of treatment regimen was made in the outpatient department. Frequent clinical and laboratory controls were performed and the patients were given full instructions for injection technique and diet. On the insulin regimen a prompt and lasting improvement was observed in the metabolic parameters (blood glucose levels both fasting and after food intake, Hb A1c, serum insulin, glucagon and serum lipid concentrations). The so-called "asymptomatic" patients noticed a marked improvement in their general status and performance. Three months after insulin therapy was started 13 of our 15 patients preferred the insulin treatment to oral agents. However, weight gain and a tendency to hypoglycemia were noticed in less disciplined patients. In addition, considerable time was spent on instruction of the patients. Bearing these factors in mind, insulin therapy in elderly diabetics with so-called "sysmptomatic hyperglycemia" can be regarded as worthwhile. PMID:515719

  3. Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

    PubMed Central

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-01-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5–7 days after the virus injection of 7 × 109 INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50–100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach. PMID:22354377

  4. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy.

    PubMed

    Zhang, Ya; Shao, Jiashen; Li, Feifei; Xu, Xianming

    2016-01-01

    Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM). Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT) were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC) were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h), and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT) alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM. PMID:27478440

  5. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy

    PubMed Central

    Zhang, Ya; Shao, Jiashen; Li, Feifei

    2016-01-01

    Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM). Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT) were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC) were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h), and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT) alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM. PMID:27478440

  6. Impact of insulin treatment in diabetic macular edema therapy in type 2 diabetes

    PubMed Central

    Matsuda, Simone; Tam, Tiffany; Singh, Rishi P.; Kaiser, Peter K.; Petkovsek, Daniel; Zanella, Maria Teresa; Ehlers, Justis P.

    2014-01-01

    Objective To evaluate the impact of insulin therapy on the outcomes of diabetic macular edema (DME) treatment with vascular endothelial growth factor (VEGF) inhibitors in type 2 diabetics. Methods A retrospective consecutive case series of 95 type 2 diabetic patients with DME treated with anti-VEGF therapy. Two cohorts were examined—patients taking only oral anti-diabetic agents and patients on insulin therapy. The main outcome measures were change in visual acuity (VA) and change in central subfield macular thickness (CST) measured by spectral-domain optical coherence tomography (SD-OCT). Additional variables analyzed included HbA1c, creatinine, blood pressure and body mass index and their correlation with clinical findings. Results Both groups had a statistical significant improvement in VA (insulin therapy group: 20/61 to 20/49, p=0.003; oral anti-diabetic agents group: 20/76 to 20/56, p=0.005). There was no difference between groups at initial or 12 month examination (p=0.239 and p=0.489, respectively). From an anatomic standpoint, CST also improved significantly in both groups [454.7 μm to 354.9 μm (p<0.001) in the oral anti-diabetic agents group and 471.5 μm to 368.4 μm (p<0.001) in the insulin therapy group]. Again, there was no significant difference between groups at initial or 12 month follow-up examination (p= 0.586 and p=0.591, respectively). Mean HBA1c levels remained relatively stable during the follow-up in both groups. Conclusion Anti-VEGF therapy is a useful treatment for DME. This study suggests that chronic insulin therapy, compared to oral anti-diabetic agents, does not modify the anatomic or functional effectiveness of DME treatment. PMID:25444681

  7. Gene Therapy for Diabetes Mellitus in Rats by Hepatic Expression of Insulin

    NASA Astrophysics Data System (ADS)

    Kolodka, Tadeusz M.; Finegold, Milton; Moss, Larry; Woo, Savio L. C.

    1995-04-01

    Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic β cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.

  8. Gene therapy for diabetes mellitus in rats by hepatic expression of insulin.

    PubMed Central

    Kolodka, T M; Finegold, M; Moss, L; Woo, S L

    1995-01-01

    Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic beta cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy. Images Fig. 3 PMID:7724555

  9. Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases.

    PubMed

    Sádaba, M C; Martín-Estal, I; Puche, J E; Castilla-Cortázar, I

    2016-07-01

    This review resumes the association between mitochondrial function and diseases, especially neurodegenerative diseases. Additionally, it summarizes the major role of IGF-1 as a mitochondrial protector, as studied in several experimental models (cirrhosis, aging …). The contribution of mitochondrial dysfunction to impairments in insulin metabolic signaling is also suggested by gene array analysis showing that reductions in gene expression, that regulates mitochondrial ATP production, are associated with insulin resistance and type 2 diabetes mellitus. Moreover, reductions in oxidative capacity of mitochondrial electron transport chain are manifested in obese, insulin-resistant and diabetic patients. Genetic and environmental factors, oxidative stress, and alterations in mitochondrial biogenesis can adversely affect mitochondrial function, leading to insulin resistance and several pathological conditions, such as type 2 diabetes. Finally, it remains essential to know the exact mechanisms involved in mitochondrial generation and metabolism, mitophagy, apoptosis, and oxidative stress to establish new targets in order to develop potentially effective therapies. One of the newest targets to recover mitochondrial dysfunction could be the administration of IGF-1 at low doses. In the last years, it has been observed that IGF-1 therapy has several beneficial effects: restores physiological IGF-1 levels; improves insulin resistance and lipid metabolism; exerts mitochondrial protection; and has hepatoprotective, neuroprotective, antioxidant and antifibrogenic effects. In consequence, treatment of mitochondrial dysfunctions with low doses of IGF-1 could be a powerful and useful effective therapy to restore normal mitochondrial functions. PMID:27020404

  10. Insulin

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The manipulation of organic materials--cells, tissues, and even living organisms--offers many exciting possibilities for the future from organic computers to improved aquaculture. Commercial researchers are using the microgravity environment to produce large near perfect protein crystals Research on insulin has yielded crystals that far surpass the quality of insulin crystals grown on the ground. Using these crystals industry partners are working to develop new and improved treatments for diabetes. Other researchers are exploring the possibility of producing antibiotics using plant cell cultures which could lead to both orbital production and the improvement of ground-based antibiotic production.

  11. Combination therapies in the management of type 2 diabetes: the use of insulin degludec/liraglutide

    PubMed Central

    Minze, Molly G; Chastain, Lisa M

    2016-01-01

    The global burden of type 2 diabetes is estimated to currently affect over 350 million people worldwide and is anticipated to continue increasing over the next 20 years. Current treatment guidelines recommend the choice of pharmacotherapy based upon patient-specific parameters, with combination therapy for patients with a hemoglobin A1c level ≥9%. A new combination therapy of insulin degludec + liraglutide provides a long-acting basal insulin with a glucagon-like peptide agonist. In clinical trials, this combination product has reduced hemoglobin A1c and fasting plasma glucose more than the individual agents alone. Further advantages observed with this combination include weight loss and decrease in hypoglycemia compared to basal insulin alone. PMID:27099505

  12. Beneficial effects of combined resveratrol and metformin therapy in treating diet-induced insulin resistance.

    PubMed

    Frendo-Cumbo, Scott; MacPherson, Rebecca E K; Wright, David C

    2016-08-01

    The polyphenol compound resveratrol (RSV) has attracted attention due to its reputed beneficial effects on insulin sensitivity. Our lab has previously identified protective effects of RSV against the development of type 2 diabetes in rats. These effects occurred in a manner similar to thiazolidinedione's (TZDs), a class of insulin sensitizing drugs. TZDs are commonly prescribed in combination with metformin (MET) and thus we sought to examine the combined effects of RSV and MET in treating insulin resistance. Male C57BL6 mice were fed a low- (LFD; 10% Kcal from fat) or high-fat diet (HFD; 60% Kcal from fat) for 9 weeks to induce glucose and insulin intolerance. HFD mice were then assigned to control (HFD), MET (231.28 ± 12.24 mg/kg/day), RSV (93.68 ± 3.51 mg/kg/day), or combined (COM; MET 232.01 ± 17.12 mg/kg/day and RSV 92.77 ± 6.92 mg/kg/day) treatment groups. Changes in glucose and insulin tolerance and tissue-specific insulin signaling were measured 4 weeks post-treatment. RSV or MET alone did not have beneficial effects on glucose tolerance, although MET significantly improved insulin tolerance compared to HFD Glucose and insulin tolerance were significantly improved in COM compared to HFD and this was mirrored by enhanced insulin-stimulated AKT phosphorylation in triceps muscle and inguinal subcutaneous adipose tissue in COM compared to HFD mice. Improvements with COM treatment were not explained by differences in body weight, adiposity, or markers of adipose tissue inflammation. In summary, this study provides evidence of beneficial effects of combined RSV and MET therapy in treating impairments in glucose homeostasis. PMID:27482073

  13. Psychological barriers to optimal insulin therapy: more concerns in adolescent females than males

    PubMed Central

    Wisting, Line; Bang, Lasse; Skrivarhaug, Torild; Dahl-Jørgensen, Knut; Rø, Øyvind

    2016-01-01

    Objective The aim of this study is to investigate psychological barriers (illness perceptions, insulin beliefs, and coping strategies) to optimal insulin therapy among adolescents with type 1 diabetes (T1D), with a specific focus on gender differences and mode of treatment (insulin pump vs pen). Methods A total of 105 males and females (12–20 years) participated in this study. The Brief Illness Perception Questionnaire, the Beliefs about Medicines Questionnaire, and the Adolescent Coping Orientation for Problem Experiences were completed. Additionally, diabetes clinical data were collected by the Norwegian Childhood Diabetes Registry. Results Females had significantly more negative illness perceptions than males on all dimensions (p<0.05), with moderate-to-large effect sizes. Regarding insulin beliefs, females scored significantly higher than males on insulin concern (p<0.001), indicating more concerns about insulin. There were no significant gender differences on perceptions of insulin necessity. Finally, females scored significantly higher on the coping strategies being social and solving family problems (p<0.01), indicating more positive coping among females than males for these subscales. In terms of treatment mode, the only statistically significant difference in the psychological aspects was for the illness perception treatment control, with patients using insulin pen reporting more negative perceptions on this dimension than patients using insulin pump. Conclusions Addressing psychological aspects may be a clinically important supplement to standard somatic T1D care. The consistent finding of gender differences across the psychological measures implies that a tailored treatment approach for males and females with T1D may be warranted. PMID:27403325

  14. Acute and chronic effects of glyceryl trinitrate therapy on insulin and glucose regulation in humans.

    PubMed

    Jedrzkiewicz, Sean; Parker, John D

    2013-05-01

    This study examined the effect of acute and sustained transdermal glyceryl trinitrate (GTN) therapy on insulin and glucose regulation. Totally, 12 males (18-30 years) underwent a glucose tolerance test at baseline (visit 1), 90 minutes after acute transdermal GTN 0.6 mg/h (visit 2), following 7 days of continuous GTN (visit 3), and 2 to 3 days after stopping GTN (visit 4). At each visit, plasma glucose and insulin concentrations were measured before and 30, 60, 90, and 120 minutes after a 75-g oral glucose load. Indices of glucose metabolism that were examined included the insulin sensitivity index, the homeostasis model assessment of insulin resistance (HOMA-IR), and the insulinogenic index. The acute administration of GTN had no effect on glucose and insulin responses (visit 2). However, after 7 days of GTN exposure (visit 3) there was an increase in the mean glucose concentration measured after the oral glucose load. On visit 1, the mean glucose concentration (± standard deviation) following the 75 g oral glucose challenge was 5.7 ± 0.5 µmol/L. On visit 3, after 7 days of transdermal GTN therapy, the mean glucose concentration after the oral glucose was significantly higher; 6.2 ± 0.5 µmol/L (P < .015; 95% confidence intervals 0.25-0.77). There was also an increase in the HOMA-IR index; on visit 1, the median HOMA-IR (interquartile range) was 5.2 (3.9) versus 6.9 (6.8) on visit 3 (P < .015). Other indices of glucose metabolism did not change. These observations document that GTN therapy modifies glucose metabolism causing evidence of increased insulin resistance during sustained therapy in normal humans. PMID:23230283

  15. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  16. Glucose-Insulin Therapy, Plasma Substrate Levels and Cardiac Recovery After Cardiac Ischemic Events

    PubMed Central

    Van Wezel, H. B.

    2008-01-01

    Introduction The potential usefulness of glucose-insulin therapy relies to a large extent on the premise that it prevents hyperglycemia and hyperlipidemia following cardiac ischemic events. Methods In this review we evaluate the literature concerning plasma glucose and free fatty acids levels during and following cardiac ischemic events. Results The data indicate that hyperlipidemia and hyperglycemia most likely occur during acute coronary ischemic syndromes in the conscious state (e.g. acute myocardial infarction) and less so during reperfusion following CABG reperfusion. This is in accordance with observations that glucose-insulin therapy during early reperfusion post CABG may actually cause hypolipidemia, because substantial hyperlipidemia does not appear to occur during that stage of cardiac surgery. Discussion Considering recent data indicating that hypolipidemia may be detrimental for cardiac function, we propose that free fatty acid levels during reperfusion post CABG with the adjunct glucose-insulin therapy need to be closely monitored. Conclusion From a clinical point of view, a strategy directed at monitoring and thereafter maintaining plasma substrate levels in the normal range for both glucose (4–6 mM) and FFA (0.2–0.6 mM) as well as stimulation of glucose oxidation, promises to be the most optimal metabolic reperfusion treatment following cardiac ischemic episodes. Future (preclinical and subsequently clinical) investigations are required to investigate whether the combination of glucose-insulin therapy with concomitant lipid administration may be beneficial in the setting of reperfusion post CABG. PMID:18266096

  17. Effects of Intensive versus Non-Intensive Physical Therapy on Children with Cerebral Palsy.

    PubMed

    Rahman, M A; Zaman, M M; Rahman, M M; Moniruzzaman, M; Ahmed, B; Chhobi, F K; Rahman, N; Akter, M R

    2016-07-01

    Cerebral Palsy (CP) is one of the most common causes of all childhood disorders. There are tone, posture and movements difficulty due to non-progressive damage to the immature brain in CP. The hallmark of CP is a disability in the development of gross motor function (GMF). The influence of gross motor development on fine motor development is more important in early developmental period, specially under three years old and in children with CP. Various therapeutic interventions have been used in the management of GMF development. Among them physical therapy is the most common intervention in CP and is usually a component of mandated programs. Physical therapy means physical stimulations in the form of various therapeutic exercises, touch, massage, limbs and trunk movement, balancing and coordination training, gait and ambulation training, cognitive stimulation as well as speech, language and occupational therapy. Our study focused to see the effect by short term intensive versus non-intensive physical therapy on children GMF development by using gross motor function measure (GMFM) Score sheet, GMFM-88, version 1.0. Study provides the information that physical therapy intervention is effective in GMF development and intensive interventions are more effective in children with spastic CP than non-intensive one. Study also inform that the more early treatment the more effective result. PMID:27612885

  18. Analgesic effect of high intensity laser therapy in knee osteoarthritis.

    PubMed

    Stiglić-Rogoznica, Nives; Stamenković, Doris; Frlan-Vrgoc, Ljubinka; Avancini-Dobrović, Viviana; Vrbanić, Tea Schnurrer-Luke

    2011-09-01

    Knee osteoarthritis (KOA), the most common type of osteoarthritis (OA), is associated with pain and inflammation of the joint capsule, impaired muscular stabilization, reduced range of motion and functional disability. High-intensity laser therapy (HILT) involves higher-intensity laser radiation and causes minor and slow light absorption by chromophores. Light stimulation of the deep structures, due to high intensity laser therapy, activates cell metabolism through photochemical effect. The transmissions of pain stimulus are slowed down and result in a quick achievement of pain relief. The aim of our research was to investigate the prompt analgesic effect of HILT on patients with KOA. Knee radiographs were performed on all patients and consequently graded using the Kellgren-Lawrence grading scale (K/L). A group of 96 patients (75 female, 21 male, mean age 59.2) with K/L 2 and 3 were submitted to HILT therapy. Pain intensity was evaluated with visual analogue scale (VAS) before and after the treatment. HILT consisted in one daily application, over a period of ten days, using protocol wavelength, frequency and duration. The results showed statistically significant decrease in VAS after the treatment (p < 0.001). Considering these results, HILT enables prompt analgesic effects in KOA treatment. Therefore HILT is a reliable option in KOA physical therapy. PMID:22220431

  19. Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

    PubMed

    Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

    2016-01-15

    Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. PMID:26644274

  20. Biphasic Insulin Aspart 30/70: Pharmacokinetics and Pharmacodynamics Compared With Once-Daily Biphasic Human Insulin and Basal-Bolus Therapy

    PubMed Central

    Heise, Tim; Heinemann, Lutz; Hövelmann, Ulrike; Brauns, Bianca; Nosek, Leszek; Haahr, Hanne L.; Olsen, Klaus J.

    2009-01-01

    OBJECTIVE Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients. RESEARCH DESIGNS AND METHODS Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h. RESULTS Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg. CONCLUSIONS BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy. PMID:19487640

  1. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach. PMID:26379428

  2. Intensive insulin treatment increases donor site wound protein synthesis in burn patients

    PubMed Central

    Tuvdendorj, Demidmaa; Zhang, Xiao-Jun; Chinkes, David L.; Aarsland, Asle; Kulp, Gabriela A.; Jeschke, Marc G.; Herndon, David N.

    2013-01-01

    Background In the treatment of burns, patients’ own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is routinely used to treat hyperglycemia after injury. We investigated whether intensive insulin treatment (INS) increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). Methods FSR of the donor site wound protein was measured in pediatric patients randomized to control (CNT) (n = 13) and INS (n = 10) treatments. Depending on the postoperative day when the tracer study was done studies were divided into “Early” (days < 5) and “Late” (days >=5) periods. Results FSR of the donor site wound protein was greater in the INS group at the “Early” period of wound healing (CNT vs. INS, 8.2±3.8 vs. 13.1±6.9 %/day, p: < 0.05); but not at the “Late” (CNT vs. INS, 19.7±4.6 vs. 16.6±4.0 %/day, p > 0.05). Despite these differences LOS/TBSA was not decreased in the INS group. Correlation analyses demonstrated that independently of the treatment regimen FSR positively correlated (p < 0.05) with time post creation of the donor site and negatively correlated (p < 0.05) with LOS/TBSA. Conclusions Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independently of the treatment regimen. PMID:21236451

  3. Devices for insulin administration.

    PubMed

    Selam, J L; Charles, M A

    1990-09-01

    There is a significant need for revised, safe, and more effective insulin-delivery methods than subcutaneous injections in the treatment of both type I (insulin-dependent) and type II (non-insulin-dependent) diabetes. The aim of this review is to describe the rationale and methods for better use of injection and infusion devices for intensive insulin therapy and to describe results of animal and human research that will lead to an implantable artificial pancreas. Injection devices, e.g., jet injectors, insulin pens, and access ports, cannot be considered as a major breakthrough in the quest for improved control, although they may improve the patient's comfort. External pumps have benefits over multiple injections and conventional insulin therapy only in specific subgroups of patients, e.g., those with recurrent severe hypoglycemia, but only when used by experienced personnel. The external artificial pancreas (Biostator) is also to be used by experienced personnel for limited clinical and research applications, e.g., surgery of the diabetic patient. The development of an implantable version of the artificial pancreas is linked to progress in the field of reliable long-duration glucose sensors. Finally, programmable implantable insulin pumps, used as an open-loop delivery system, are the most promising alternative to intensive subcutaneous insulin strategies in the short term, although clear evidence of improved safety and efficacy remains to be documented. PMID:2226111

  4. Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus.

    PubMed

    Yki-Järvinen, Hannele

    2002-01-01

    The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes. PMID:12324990

  5. Cortical thinning in type 2 diabetes mellitus and recovering effects of insulin therapy.

    PubMed

    Chen, Zhiye; Sun, Jie; Yang, Yang; Lou, Xin; Wang, Yulin; Wang, Yan; Ma, Lin

    2015-02-01

    The purpose of this study was to explore the brain structural changes in type 2 diabetes and the effect of insulin on the brain using a surface-based cortical thickness analysis. High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI were obtained from 11 patients with type 2 diabetes before and after insulin therapy. The cortical thickness over the entire brain was calculated, and cross-sectional and longitudinal surface-based cortical thickness analyses were also performed. Regional cortical thinning was demonstrated in the middle temporal gyrus, posterior cingulate gyrus, precuneus, right lateral occipital gyrus and entorhinal cortex bilaterally for patients with type 2 diabetes mellitus compared with normal controls. Cortical thickening was seen in the middle temporal gyrus, entorhinal cortex and left inferior temporal gyrus bilaterally after patients underwent 1 year of insulin therapy. These findings suggest that insulin therapy may have recovering effects on the brain cortex in type 2 diabetes mellitus. The precise mechanism should be investigated further. PMID:25439756

  6. Improving the efficacy of type 1 diabetes therapy by transplantation of immunoisolated insulin-producing cells.

    PubMed

    Ngoc, Phan Kim; Phuc, Pham Van; Nhung, Truong Hai; Thuy, Duong Thanh; Nguyet, Nguyen Thi Minh

    2011-06-01

    Type 1 diabetes occurs when pancreatic islet β-cells are damaged and are thus unable to secrete insulin. Pancreas- or islet-grafting therapy offers highly efficient treatment but is limited by inadequate donor islets or pancreases for transplantation. Stem-cell therapy holds tremendous potential and promises to enhance treatment efficiency by overcoming the limitations of traditional therapies. In this study, we evaluated the efficiency of preclinical diabetic treatment. Diabetes was induced in mice by injections of streptozotocin. Mesenchymal stem cells (MSCs) were derived from mouse bone marrow or human umbilical cord blood and subsequently differentiated into insulin-producing cells. These insulin-producing cells were encapsulated in an alginate membrane to form capsules. Finally, these capsules were grafted into diabetic mice by intraperitoneal injection. Treatment efficiency was evaluated by monitoring body weight and blood glucose levels. Immune reactions after transplantation were monitored by counting total white blood cells. Allografting or xenografting of encapsulated insulin-producing cells (IPCs) reduced blood glucose levels and increased body weight following transplantation. Encapsulation with alginate conferred immune isolation and prevented graft rejection. These results provide further evidence supporting the use of allogeneic or xenogeneic MSCs obtained from bone marrow or umbilical cord blood for treating type 1 diabetes. PMID:21567289

  7. A review of low-intensity ultrasound for cancer therapy.

    PubMed

    Wood, Andrew K W; Sehgal, Chandra M

    2015-04-01

    The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy-sonodynamic therapy, ultrasound-mediated chemotherapy, ultrasound-mediated gene delivery and anti-vascular ultrasound therapy-was reviewed. Each technique consistently resulted in the death of cancer cells, and the bio-effects of ultrasound were attributed primarily to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform that can monitor the success of anti-cancer therapy. Little attention, however, has been given either to the direct assessment of the mechanisms underlying the observed bio-effects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data, there could be prompt application of a therapy technique in the treatment of cancer patients. PMID:25728459

  8. High Intensity Focused Ultrasound Tumor Therapy System and Its Application

    NASA Astrophysics Data System (ADS)

    Sun, Fucheng; He, Ye; Li, Rui

    2007-05-01

    At the end of last century, a High Intensity Focused Ultrasound (HIFU) tumor therapy system was successfully developed and manufactured in China, which has been already applied to clinical therapy. This article aims to discuss the HIFU therapy system and its application. Detailed research includes the following: power amplifiers for high-power ultrasound, ultrasound transducers with large apertures, accurate 3-D mechanical drives, a software control system (both high-voltage control and low-voltage control), and the B-mode ultrasonic diagnostic equipment used for treatment monitoring. Research on the dosage of ultrasound required for tumour therapy in multiple human cases has made it possible to relate a dosage formula, presented in this paper, to other significant parameters such as the volume of thermal tumor solidification, the acoustic intensity (I), and the ultrasound emission time (tn). Moreover, the HIFU therapy system can be applied to the clinical treatment of both benign and malignant tumors in the pelvic and abdominal cavity, such as uterine fibroids, liver cancer and pancreatic carcinoma.

  9. An arc-sequencing algorithm for intensity modulated arc therapy

    SciTech Connect

    Shepard, D. M.; Cao, D.; Afghan, M. K. N.; Earl, M. A.

    2007-02-15

    Intensity modulated arc therapy (IMAT) is an intensity modulated radiation therapy delivery technique originally proposed as an alternative to tomotherapy. IMAT uses a series of overlapping arcs to deliver optimized intensity patterns from each beam direction. The full potential of IMAT has gone largely unrealized due in part to a lack of robust and commercially available inverse planning tools. To address this, we have implemented an IMAT arc-sequencing algorithm that translates optimized intensity maps into deliverable IMAT plans. The sequencing algorithm uses simulated annealing to simultaneously optimize the aperture shapes and weights throughout each arc. The sequencer enforces the delivery constraints while minimizing the discrepancies between the optimized and sequenced intensity maps. The performance of the algorithm has been tested for ten patient cases (3 prostate, 3 brain, 2 head-and-neck, 1 lung, and 1 pancreas). Seven coplanar IMAT plans were created using an average of 4.6 arcs and 685 monitor units. Additionally, three noncoplanar plans were created using an average of 16 arcs and 498 monitor units. The results demonstrate that the arc sequencer can provide efficient and highly conformal IMAT plans. An average sequencing time of approximately 20 min was observed.

  10. Optimizing antibiotic therapy in the intensive care unit setting

    PubMed Central

    Kollef, Marin H

    2001-01-01

    Antibiotics are one of the most common therapies administered in the intensive care unit setting. In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms. Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance. This review will present several strategies aimed at achieving optimal use of antimicrobial agents. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de-escalation therapy) be evaluated at the local level. PMID:11511331

  11. High-Intensity Focused Ultrasound Therapy: an Overview for Radiologists

    PubMed Central

    Kim, Young-sun; Choi, Min Joo; Lim, Hyo Keun; Choi, Dongil

    2008-01-01

    High-intensity focused ultrasound therapy is a novel, emerging, therapeutic modality that uses ultrasound waves, propagated through tissue media, as carriers of energy. This completely non-invasive technology has great potential for tumor ablation as well as hemostasis, thrombolysis and targeted drug/gene delivery. However, the application of this technology still has many drawbacks. It is expected that current obstacles to implementation will be resolved in the near future. In this review, we provide an overview of high-intensity focused ultrasound therapy from the basic physics to recent clinical studies with an interventional radiologist's perspective for the purpose of improving the general understanding of this cutting-edge technology as well as speculating on future developments. PMID:18682666

  12. Oxygen therapy in neonatal intensive care units in Khartoum State

    PubMed Central

    Omer, Ilham M; Ibrahim, Nada G; Nasr, Abdalhalim M A

    2015-01-01

    Oxygen is a drug that is essential in the treatment and prevention of neonatal hypoxia. The goal of oxygen therapy is to deliver sufficient oxygen to tissues while minimizing oxygen toxicity and oxidative stress. Improvement in monitoring technology of oxygen therapy has helped to improve clinicians’ ability to appropriately apply and deliver oxygen. The objectives of this prospective observational descriptive hospital based study were: to evaluate the practice of oxygen therapy in the neonatal intensive care units (NICUs) in Khartoum State, to identify guidelines of oxygen therapy in NICUs, to determine the mode of oxygen delivery to the neonates, and to assess the practice of long term follow up of patients who used oxygen. During the period January – June 2014, 139 neonates were included. Oxygen was delivered to the neonates in the study depending on the clinical assessment. Saturation was not measured at the time of oxygen administration in 119 (85.6%) neonates. Oxygen was delivered by central device in 135 neonates (97.1%). The majority of the staff did not know the practice of long-term follow up. Hundred and sixteen (83.5%) of the nursing staff knew that oxygen has complications but the majority didn’t know the nature of the complications and what causes them. The study showed that there is lack of guidelines of oxygen therapy in the NICUs and lack of monitoring procedures, which is important to be highlighted to overcome the complications and to improve the practice of oxygen therapy.

  13. Optimization, delivery and evaluation of intensity modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Oliver, Michael R.

    Intensity modulated arc therapy (IMAT) is a radiation therapy technique whereby the shape of the cone beam of radiation changes as it rotates around the patient. This is in contrast to other more commonly delivered forms of advanced radiation therapy, Intensity Modulated Radiation Therapy (IMRT) or helical tomotherapy. IMRT is a radiation technique where a patient is treated with a cone beam of radiation from a number of fixed beam directions, where the shapes and weights of the radiation beams are varied and tomotherapy is treated with a fan beam of radiation that follows a helical trajectory. In this thesis two aspects of IMAT were investigated: optimization of treatment plans and delivery of plans in conjunction with and without respiratory motion management. Optimization of IMAT deliveries consisted of two studies. In the first study, an algorithm that uses dosimetric ray tracing to set multi-leaf collimator (MLC) positions then directly optimizes the MLC positions to create IMAT treatment plans with only beam shape variations was developed and tested in three phantom studies and a clinical case. The second study investigated variable angular dose rate deliveries to a concave target and assessed the optimization strategy including arc initialization strategy, angular sampling and delivery efficiency. IMAT delivery with and without respiratory gated radiation delivery was studied with dose measurement using radiographic film in a motion phantom. In addition, simulations based on delivered log files were used to confirm that motion management for IMAT is effective and within dosimetric tolerances. As a pilot test, plans from IMRT and tomotherapy for partial breast irradiation were first studied, comparing them to conventional treatments. An IMAT plan was generated for one patient, demonstrating feasibility and was compared with IMRT and tomotherapy. This thesis has introduced a new IMAT optimization algorithm with and without variable angular dose rate, applied

  14. The Efficacy of Vildagliptin Concomitant With Insulin Therapy in Type 2 Diabetic Subjects

    PubMed Central

    Ito, Daisuke; Inoue, Kazuyuki; Kaneko, Kimie; Yanagisawa, Morifumi; Sumita, Takashi; Ikegami, Yuichi; Awata, Takuya; Ishida, Hitoshi; Katayama, Shigehiro; Inukai, Kouichi

    2015-01-01

    Background In Japan, dipeptidyl peptidase 4 (DPP4) inhibitors have become standard therapeutic agents for type 2 diabetes, and numbers of patients receiving insulin therapy combined with DPP4 inhibitors, which is a highly effective regimen, are increasing. Methods In this study, we evaluated the efficacy of vildagliptin administered at the dose of 100 mg twice daily in 57 patients with type 2 diabetes already receiving insulin treatment. Results The 36 patients who simply received add-on vildagliptin showed a 0.6% decrease in HbA1c levels, despite a marked insulin dose reduction, mainly bolus insulin, of approximately 8.3 units. In addition, body mass index exhibited a significant negative correlation with the efficacy of vildagliptin, i.e., ΔHbA1c. On the other hand, the 21 patients switched from 50 mg of sitagliptin to vildagliptin showed HbA1c decreases approaching 0.7%. Conclusion Taking into consideration that twice-daily oral vildagliptin has already been reported to be advantageous in reducing postprandial hyperglycemia, this drug was suggested to be more effective in reducing HbA1c than sitagliptin under conditions in which it is used as a supplement to basal insulin, as in this study. PMID:25780477

  15. Redesigning an intensive insulin service for patients with type 1 diabetes: a patient consultation exercise

    PubMed Central

    Ozcan, Seyda; Rogers, Helen; Choudhary, Pratik; Amiel, Stephanie A; Cox, Alison; Forbes, Angus

    2013-01-01

    Context Providing effective support for patients in using insulin effectively is essential for good diabetes care. For that support to be effective it must reflect and attend to the needs of patients. Purpose To explore the perspectives of adult type 1 diabetes patients on their current diabetes care in order to generate ideas for creating a new patient centered intensive insulin clinic. Methods A multi-method approach was used, comprising: an observational exercise of current clinical care; three focus groups (n = 17); and a survey of service users (n = 419) to test the ideas generated from the observational exercise and focus groups (rating 1 to 5 in terms of importance). The ideas generated by the multi-method approach were organized thematically and mapped onto the Chronic Care Model (CCM). Results The themes and preferences for service redesign in relation to CCM components were: health care organization, there was an interest in having enhanced systems for sharing clinical information; self-management support, patients would like more flexible and easy to access resources and more help with diabetes technology and psychosocial support; delivery system design and clinical information systems, the need for greater integration of care and better use of clinic time; productive relationships, participants would like more continuity; access to health professionals, patient involvement and care planning. The findings from the patient survey indicate high preferences for most of the areas for service enhancement identified in the focus groups and observational exercise. Clinical feedback and professional continuity (median = 5, interquartile range = 1) were the most highly rated. Conclusion The patient consultation process had generated important ideas on how the clinical team and service can improve the care provided. Key areas for service development were: a stronger emphasis of collaborative care planning; improved patient choice in the use of health technology

  16. Personalized intensification of insulin therapy in type 2 diabetes - does a basal-bolus regimen suit all patients?

    PubMed

    Giugliano, D; Sieradzki, J; Stefanski, A; Gentilella, R

    2016-08-01

    Many patients with type 2 diabetes mellitus (T2DM) require insulin therapy. If basal insulin fails to achieve glycemic control, insulin intensification is one possible treatment intensification strategy. We summarized clinical data from randomized clinical trials designed to compare the efficacy and safety of basal-bolus and premixed insulin intensification regimens. We defined a between-group difference of ≥0.3% in end-of-study glycated hemoglobin (HbA1c) as clinically meaningful. A PubMed database search supplemented by author-identified papers yielded 15 trials which met selection criteria: randomized design, patients with T2DM receiving basal-bolus (bolus injection ≤3 times/day) vs. premixed (≤3 injections/day) insulin regimens, primary/major endpoint(s) HbA1c- and/or hypoglycemia-related, and trial duration ≥12 weeks. Glycemic control improved with both basal-bolus and premixed insulin regimens with - in most cases - acceptable levels of weight gain and hypoglycemia. A clinically meaningful difference between regimens in glycemic control was recorded in only four comparisons, all of which favored basal-bolus therapy. The incidence of hypoglycemia was significantly different between regimens in only three comparisons, one of which favored premixed insulin and two basal-bolus therapy. Of the four trials that reported a significant difference between regimens in bodyweight change, two favored basal-bolus therapy and two favored premixed insulin. Thus, on a population level, neither basal-bolus therapy nor premixed insulin showed a consistent advantage in terms of glycemic control, hypoglycemic risk, or bodyweight gain. It is therefore recommended that clinicians should adopt an individualized approach to insulin intensification - taking into account the benefits and risks of each treatment approach and the attitude and preferences of each patient - in the knowledge that both basal-bolus and premixed regimens may be successful. PMID:27126277

  17. Combined therapy of insulin-producing cells and haematopoietic stem cells offers better diabetic control than only haematopoietic stem cells’ infusion for patients with insulin-dependent diabetes

    PubMed Central

    Dave, Shruti D; Trivedi, Hargovind L; Gopal, Saroj C; Chandra, Tulika

    2014-01-01

    Insulin-dependent diabetes mellitus (IDDM) is a chronic condition characterised by impaired blood sugar metabolism and autoimmunity. We report two children: a 5-year-old girl on exogenous insulin therapy of 30 IU/day and a 9-year-old boy on short-acting insulin 30 IU/day, long-acting insulin 70 IU/day, with IDDM since 4 and 7 years, respectively. We infused in vitro-generated donor bone marrow (BM)-derived haematopoietic stem cells (HSC) in patient 1 and insulin-secreting cells trans-differentiated from autologous adipose tissue-derived mesenchymal stem cells along with BM-HSC in patient 2 under non-myeloablative conditioning. Patient 1 improved during the initial 6 months, but then again lost metabolic control with increased blood sugar levels and insulin requirement of 32 IU/day; we lost her to follow-up after 18 months. Patient 2, over follow-up of 24.87 months, has stable blood sugar levels with glycosylated haemoglobin of 6.4% and present insulin requirement of 15 IU/day. PMID:25199184

  18. Advances in endonasal low intensity laser irradiation therapy

    NASA Astrophysics Data System (ADS)

    Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

    2005-07-01

    Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

  19. Hormone resuscitation therapy for brain-dead donors - is insulin beneficial or detrimental?

    PubMed

    Novitzky, Dimitri; Mi, Zhibao; Videla, Luis A; Collins, Joseph F; Cooper, David K C

    2016-07-01

    Hormonal replacement therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63 593 donors in whom information on thyroid hormone therapy (triiodothyronine or levothyroxine [T3 /T4 ]) was available. In 40 124 donors, T3 /T4 and all other hormonal therapy were recorded. The percentage of all organs procured, except livers, was greater when T3 /T4 had been administered. An independent beneficial effect of antidiuretic hormone (ADH) was also clear. Corticosteroids were less consistently beneficial (most frequently when T3 /T4 had not been administered), although never detrimental. Insulin was almost never beneficial and at times was associated with a reduced yield of organs, particularly of the pancreas and intestine, an observation that does not appear to have been reported previously. In addition, there was reduced survival at 12 months of recipients of pancreases from T3 /T4 -treated donors, but not of pancreas grafts. The possibly detrimental effect observed following insulin therapy is discussed. PMID:27037748

  20. Clinical recommendations in the management of the patient with type 1 diabetes on insulin pump therapy in the perioperative period: a primer for the anaesthetist.

    PubMed

    Partridge, H; Perkins, B; Mathieu, S; Nicholls, A; Adeniji, K

    2016-01-01

    Insulin pump therapy is increasingly common in patients with type 1 diabetes. Many of these patients will require surgery at some point in their lifetime. Few doctors will have experience of managing these patients, and little evidence exists to assist in the development of guidelines for patients with insulin pump therapy, undergoing surgery.It is clear that during emergency surgery insulin pump therapy is not appropriate and should be discontinued, but patients undergoing some elective surgery can and should continue insulin pump therapy, without any adverse effect on their blood sugar control, or on the outcome of their surgery. Individual hospitals need to formalize guidance on the management of patients receiving continuous subcutaneous insulin therapy, to allow patients the choice to continue their therapy during surgery. This expert opinion presents anaesthetists with a suggested clinical framework to help facilitate continued insulin pump therapy, during elective surgery and into the postoperative period. PMID:26675948

  1. Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics.

    PubMed

    Garnier-Sagne, I; Leblanc, J C; Verger, P

    2001-07-01

    In 1994, European Directive 94/35/CE authorised the use as food additives of five intense sweeteners for which Acceptable Daily Intakes (ADI) were established. The same directive stipulated that member states should organise a monitoring system to determine the consumption of these substances. Diabetic children are normally considered to constitute a group with a high consumption of sweeteners (European Commission, 1998. Report on Methodology for the Monitoring of Food Additives Intake across the European Union. Report of the Scientific Cooperation, Task 4.2 SCOOP/INT/REPORT/2. European Commission Directorate General III, Brussels.). A stepwise approach to the food additive intake in the general population had shown that three of the five authorised intense sweeteners (aspartame, saccharin and acesulfame K) are used at particularly high levels in sugar-free foods and are also very commonly utilised as table-top sweeteners. This paper presents the results of a food intake survey conducted in a group of French, insulin-dependent children in 1997, aimed at estimating the Theoretical Maximum Daily Intake (TMDI) for these three sweeteners and comparing this with the relevant ADI values. A 5-day diary questionnaire was used to estimate the intake of sugar-free, artificially sweetened foods and table-top sweeteners. When assessing the intake of each additive, all sugar-free products were assumed to be sweetened using a single sweetener at its maximum authorised level. This study was performed in five age groups, and based on the mean and 97.5th percentile of the distribution of consumption, demonstrated that it was unlikely that total exposure could rise above the ADI. PMID:11397521

  2. Insulin therapy in burn patients does not contribute to hepatic triglyceride production.

    PubMed Central

    Aarsland, A; Chinkes, D L; Sakurai, Y; Nguyen, T T; Herndon, D N; Wolfe, R R

    1998-01-01

    Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin

  3. Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoguang; Li, Jie; Liu, Timon Chengyi; Yuan, Jianqin; Luo, Qingming

    2008-12-01

    The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

  4. Segmentation and leaf sequencing for intensity modulated arc therapy

    SciTech Connect

    Gladwish, Adam; Oliver, Mike; Craig, Jeff; Chen, Jeff; Bauman, Glenn; Fisher, Barbara; Wong, Eugene

    2007-05-15

    A common method in generating intensity modulated radiation therapy (IMRT) plans consists of a three step process: an optimized fluence intensity map (IM) for each beam is generated via inverse planning, this IM is then segmented into discrete levels, and finally, the segmented map is translated into a set of MLC apertures via a leaf sequencing algorithm. To date, limited work has been done on this approach as it pertains to intensity modulated arc therapy (IMAT), specifically in regards to the latter two steps. There are two determining factors that separate IMAT segmentation and leaf sequencing from their IMRT equivalents: (1) the intrinsic 3D nature of the intensity maps (standard 2D maps plus the angular component), and (2) that the dynamic multileaf collimator (MLC) constraints be met using a minimum number of arcs. In this work, we illustrate a technique to create an IMAT plan that replicates Tomotherapy deliveries by applying IMAT specific segmentation and leaf-sequencing algorithms to Tomotherapy output sinograms. We propose and compare two alternative segmentation techniques, a clustering method, and a bottom-up segmentation method (BUS). We also introduce a novel IMAT leaf-sequencing algorithm that explicitly takes leaf movement constraints into consideration. These algorithms were tested with 51 angular projections of the output leaf-open sinograms generated on the Hi-ART II treatment planning system (Tomotherapy Inc.). We present two geometric phantoms and 2 clinical scenarios as sample test cases. In each case 12 IMAT plans were created, ranging from 2 to 7 intensity levels. Half were generated using the BUS segmentation and half with the clustering method. We report on the number of arcs produced as well as differences between Tomotherapy output sinograms and segmented IMAT intensity maps. For each case one plan for each segmentation method is chosen for full Monte Carlo dose calculation (NumeriX LLC) and dose volume histograms (DVH) are calculated

  5. The association of intensity and overall level of physical activity energy expenditure with a marker of insulin resistance

    PubMed Central

    Assah, F. K.; Brage, S.; Wareham, N. J.

    2008-01-01

    Aims/hypothesis Physical activity is important in preventing insulin resistance, but it is unclear which dimension of activity confers this benefit. We examined the association of overall level and intensity of physical activity with fasting insulin level, a marker of insulin resistance. Methods This was a cross-sectional analysis of the Medical Research Council Ely population-based cohort study (2000–2002). Physical activity energy expenditure (PAEE) in kJ kg−1 min−1 was measured by heart rate monitoring with individual calibration over a period of 4 days. The percentage of time spent above 1.5, 1.75 and 2 times resting heart rate (RHR) represented all light-to-vigorous, moderate-to-vigorous and vigorous activity, respectively. Results Data from a total of 643 non-diabetic individuals (319 men, 324 women) aged 50 to 75 years were analysed. In multivariate linear regression analyses, adjusting for age, sex and body fat percentage, PAEE was significantly associated with fasting insulin (pmol/l) (β = −0.875, p = 0.006). Time (% of total) spent above 1.75 × RHR and also time spent above 2 × RHR were both significantly associated with fasting insulin (β = −0.0109, p = 0.007 and β = −0.0365, p = 0.001 respectively), after adjusting for PAEE, age, sex and body fat percentage. Time spent above 1.5 × RHR was not significantly associated with fasting insulin in a similar model (β = −0.0026, p = 0.137). Conclusions/interpretation The association between PAEE and fasting insulin level, a marker of insulin resistance, may be attributable to the time spent in moderate-to-vigorous and vigorous activity, but not to time spent in light-intensity physical activity. PMID:18488189

  6. Intensity-Modulated Arc Therapy for Pediatric Posterior Fossa Tumors

    SciTech Connect

    Beltran, Chris; Gray, Jonathan; Merchant, Thomas E.

    2012-02-01

    Purpose: To compare intensity-modulated arc therapy (IMAT) to noncoplanar intensity-modulated radiation therapy (IMRT) in the treatment of pediatric posterior fossa tumors. Methods and Materials: Nine pediatric patients with posterior fossa tumors, mean age 9 years (range, 6-15 years), treated using IMRT were chosen for this comparative planning study because of their tumor location. Each patient's treatment was replanned to receive 54 Gy to the planning target volume (PTV) using five different methods: eight-field noncoplanar IMRT, single coplanar IMAT, double coplanar IMAT, single noncoplanar IMAT, and double noncoplanar IMAT. For each method, the dose to 95% of the PTV was held constant, and the doses to surrounding critical structures were minimized. The different plans were compared based on conformity, total linear accelerator dose monitor units, and dose to surrounding normal tissues, including the entire body, whole brain, temporal lobes, brainstem, and cochleae. Results: The doses to the target and critical structures for the various IMAT methods were not statistically different in comparison with the noncoplanar IMRT plan, with the following exceptions: the cochlear doses were higher and whole brain dose was lower for coplanar IMAT plans; the cochleae and temporal lobe doses were lower and conformity increased for noncoplanar IMAT plans. The advantage of the noncoplanar IMAT plan was enhanced by doubling the treatment arc. Conclusion: Noncoplanar IMAT results in superior treatment plans when compared to noncoplanar IMRT for the treatment of posterior fossa tumors. IMAT should be considered alongside IMRT when treatment of this site is indicated.

  7. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  8. Influence Of Low Intensity Laser Therapy On Diabetic Polyneuropathy

    NASA Astrophysics Data System (ADS)

    Abdel-Raoof, N. A.; Elnhas, N. G.; Elsayed, I. M.

    2011-09-01

    Diabetic peripheral neuropathy is a consequence of diabetes-mediated impairment of blood flow, and resultant hypoxia of nerves that may develop within 10 years of the onset of diabetes in 40-50% of people with type 1 or type 2 diabetes. Low Intensity Laser Therapy (LILT) has been advocated for the treatment of chronic pain disorders as blood flow is an important determinant for pain relief. Comparing the effect of Helium-Neon Laser therapy versus Infrared laser therapy on blood vessels diameter and flow as well as level of sensation for neuropathy. Twenty diabetic patients suffering from neuropathy were enrolled in the study with age 45-55 years. They were assigned randomly into two equal groups in number; Group A underwent an application of He-Neon laser while Group B underwent an application of Infrared laser. Both groups received laser for 2 months. Blood flow velocity, and blood vessel diameter were investigated by using duplex Doppler ultrasound and peripheral neuropathy parameters were investigated by Semmes-Weinstein monofilament assessment. The results revealed that He-Neon laser as well as Infrared laser groups showed significant improvement in blood flow velocity, blood vessel diameter & neuropathy tested parameters after treatment but there was no significance difference between the two types of LILT. LILT is a safe, non-invasive and drug free method for improving blood flow & sensation in patients suffering from diabetic polyneuropathy in addition to preventing one of the most threatening microvascular complications of diabetes.

  9. Stepwise intensification of insulin therapy in Type 2 diabetes management—exploring the concept of the basal-plus approach in clinical practice

    PubMed Central

    Owens, D R

    2013-01-01

    Basal insulin provides an effective method for initiating insulin therapy in people with Type 2 diabetes, resulting in significant improvements in glycaemic control, lower rates of hypoglycaemia and less weight gain than either prandial or premixed insulin regimens. However, the progressive nature of Type 2 diabetes and the inability of basal insulin to correct excessive postprandial glucose excursions mean that insulin therapy will eventually need to be intensified, typically by adding prandial insulin as part of a basal–bolus or premixed insulin regimen. The aim of this review is to summarize recent clinical evidence for a staged ‘basal-plus’ strategy for insulin intensification where one, two or three prandial insulin injections are added to basal insulin according to individual need. In the early stages of insulin therapy, most individuals seem to achieve favourable glycaemic control with basal insulin alone, or in combination with a single prandial insulin injection. The addition of a single prandial insulin injection at the largest meal is well tolerated and associated with significant improvements in glycated haemoglobin (HbA1c), low rates of hypoglycaemia and limited weight gain. More people achieve recommended HbA1c targets with a basal-plus strategy, compared with twice-daily premixed insulin therapy, with lower rates of hypoglycaemia. The data indicate that a step-by-step approach with the basal-plus strategy is a promising alternative method of insulin intensification that allows for individualization of treatment and may delay progression to a full basal–bolus insulin replacement therapy for many individuals. PMID:22998363

  10. Comparison of intensity modulated x-ray therapy and intensity modulated proton therapy for selective subvolume boosting: a phantom study

    NASA Astrophysics Data System (ADS)

    Flynn, R. T.; Barbee, D. L.; Mackie, T. R.; Jeraj, R.

    2007-10-01

    Selective subvolume boosting can theoretically improve tumour control probability while maintaining normal tissue complication probabilities similar to those of uniform dose distributions. In this work the abilities of intensity-modulated x-ray therapy (IMXT) and intensity-modulated proton therapy (IMPT) to deliver boosts to multiple subvolumes of varying size and proximities are compared in a thorough phantom study. IMXT plans were created using the step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) methods. IMPT plans were created with the spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT) methods. IMPT-DGT is a generalization of the distal edge tracking method designed to reduce the number of proton beam spots required to deliver non-uniform dose distributions relative to IMPT-SS. The IMPT methods were delivered over both 180° and 360° arcs. The IMXT-SAS and IMPT-SS methods optimally satisfied the non-uniform dose prescriptions the least and the most, respectively. The IMPT delivery methods reduced the normal tissue integral dose by a factor of about 2 relative to the IMXT delivery methods, regardless of the delivery arc. The IMPT-DGT method reduced the number of proton beam spots by a factor of about 3 relative to the IMPT-SS method.

  11. Concentrations of Insulin Glargine and Its Metabolites During Long-Term Insulin Therapy in Type 2 Diabetic Patients and Comparison of Effects of Insulin Glargine, Its Metabolites, IGF-I, and Human Insulin on Insulin and IGF-I Receptor Signaling

    PubMed Central

    Varewijck, Aimee J.; Yki-Järvinen, Hannele; Schmidt, Ronald; Tennagels, Norbert; Janssen, Joseph A.M.J.L.

    2013-01-01

    We investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m2, and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography–tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9–2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes. PMID:23569175

  12. Hypoglycemia, With or Without Insulin Therapy, Is Associated With Increased Mortality Among Hospitalized Patients

    PubMed Central

    Garg, Rajesh; Hurwitz, Shelley; Turchin, Alexander; Trivedi, Apoorva

    2013-01-01

    OBJECTIVE Hypoglycemia is associated with increased mortality in hospitalized patients. We investigated the relationship between spontaneous hypoglycemia versus insulin-associated hypoglycemia and mortality in hospitalized patients. RESEARCH DESIGN AND METHODS Data for this retrospective cohort study were obtained from electronic databases of patients admitted between 1 April 2008 and 30 November 2010. Patients with one or more blood glucose values ≤50 mg/dL on point-of-care glucose testing were considered hypoglycemic. Patients treated with insulin were assumed to have insulin-associated hypoglycemia. Age-, sex-, and race-matched patients with all blood glucose values >70 mg/dL were selected as controls. The Charlson comorbidity index (CCI) was used to control for severity of illness. RESULTS There were four groups: 1) noninsulin-treated hypoglycemia (NTH) (n = 135), 2) insulin-treated hypoglycemia (ITH) (n = 961), 3) noninsulin-treated control (NTC) (n = 1,058), and 4) insulin-treated control (ITC) (n = 736). Mortality was higher in the ITH group compared with the ITC group (20.3 vs. 4.5%, P < 0.0001), with a relatively higher CCI (1.8 vs. 1.5%, P < 0.0001), but much higher in the NTH group compared with the NTC group (34.5 vs. 1.1%, P < 0.0001), with much higher CCI (2.4 vs. 1.1%, P < 0.0001). Mortality was higher in the NTH group compared with the ITH group (P < 0.0001) but lower in the NTC group compared with the ITC group (P < 0.0001). After controlling for age, sex, CCI, and admission to the intensive care unit, insulin treatment was associated with a lower mortality among the hypoglycemic patients; hazard ratio of death in the ITH group relative to the NTH group was 0.34 (95% CI 0.25–0.47, P < 0.0001). CONCLUSIONS Insulin-associated and spontaneous hypoglycemia are associated with increased mortality among hospitalized patients. PMID:23248192

  13. Clinical Implementation of Intensity Modulated Proton Therapy for Thoracic Malignancies

    SciTech Connect

    Chang, Joe Y.; Li, Heng; Zhu, X. Ronald; Liao, Zhongxing; Zhao, Lina; Liu, Amy; Li, Yupeng; Sahoo, Narayan; Poenisch, Falk; Gomez, Daniel R.; Wu, Richard; Gillin, Michael; Zhang, Xiaodong

    2014-11-15

    Purpose: Intensity modulated proton therapy (IMPT) can improve dose conformality and better spare normal tissue over passive scattering techniques, but range uncertainties complicate its use, particularly for moving targets. We report our early experience with IMPT for thoracic malignancies in terms of motion analysis and management, plan optimization and robustness, and quality assurance. Methods and Materials: Thirty-four consecutive patients with lung/mediastinal cancers received IMPT to a median 66 Gy(relative biological equivalence [RBE]). All patients were able to undergo definitive radiation therapy. IMPT was used when the treating physician judged that IMPT conferred a dosimetric advantage; all patients had minimal tumor motion (<5 mm) and underwent individualized tumor-motion dose-uncertainty analysis and 4-dimensional (4D) computed tomographic (CT)-based treatment simulation and motion analysis. Plan robustness was optimized by using a worst-case scenario method. All patients had 4D CT repeated simulation during treatment. Results: IMPT produced lower mean lung dose (MLD), lung V{sub 5} and V{sub 20}, heart V{sub 40}, and esophageal V{sub 60} than did IMRT (P<.05) and lower MLD, lung V{sub 20}, and esophageal V{sub 60} than did passive scattering proton therapy (PSPT) (P<.05). D{sub 5} to the gross tumor volume and clinical target volume was higher with IMPT than with intensity modulated radiation therapy or PSPT (P<.05). All cases were analyzed for beam-angle-specific motion, water-equivalent thickness, and robustness. Beam angles were chosen to minimize the effect of respiratory motion and avoid previously treated regions, and the maximum deviation from the nominal dose-volume histogram values was kept at <5% for the target dose and met the normal tissue constraints under a worst-case scenario. Patient-specific quality assurance measurements showed that a median 99% (range, 95% to 100%) of the pixels met the 3% dose/3 mm distance criteria for the

  14. Emotional exhaustion and defense mechanisms in intensive therapy unit nurses.

    PubMed

    Regan, Anna; Howard, Ruth A; Oyebode, Jan R

    2009-05-01

    Contrary to its original conceptualization, research has found that emotional demands do not lead to burnout in nurses. According to psychoanalytic theory, unconscious defense mechanisms may protect nurses from conscious awareness of work-related anxiety. This prevents self-report and may explain research findings. The maturity of defense style influences how anxiety is managed. Immature defenses prevent the conscious processing necessary for resolution of anxiety. Therefore, it is hypothesized that the use of immature defenses will lead to emotional exhaustion. This cross-sectional study used questionnaires to explore the defense mechanisms of 87 Intensive Therapy Unit nurses. Although the sample endorsed a predominantly mature defense style, the use of immature defenses predicted emotional exhaustion. Also, lower levels of reported stress associated with emotional demands predicted emotional exhaustion. Although this strongly implies the mediating role of immature defense mechanisms, the results were not statistically significant. PMID:19440106

  15. Basic studies on intravascular low-intensity laser therapy

    NASA Astrophysics Data System (ADS)

    Liu, Timon Cheng-Yi; Duan, Rui; Wang, Shuang-Xi; Liu, Jiang; Cui, Li-Ping; Jin, Hua; Liu, Song-Hao

    2006-09-01

    Intravascular low intensity laser therapy (ILILT) was originally put forward in USA in 1982, but popularized in Russia in 1980s and in China in 1990s, respectively. A randomized placebo-controlled study has shown ILILT clinical efficacy in patients suffering from rheumatoid arthritis. As Chinese therapeutic applications of ILILT were the most widely in the world, its basic research, such as intracellular signal transduction research, blood research in vitro, animal blood research in vivo, human blood research in vivo and traditional Chinese medicine research, was also very progressive in China. Its basic studies will be reviewed in terms of the biological information model of photobiomodulation in this paper. ILILT might work in view of its basic studies, but the further randomized placebo-controlled trial and the further safety research should be done.

  16. New Dosimetry Technologies for Imrt (intensity Modulated Radio Therapy)

    NASA Astrophysics Data System (ADS)

    Piermattei, A.; Cilla, S.; Pepe, D.; Grimaldi, L.; Craus, M.; Fidanzio, A.; Azario, L.; Dell'Omo, C.; Pasciuti, K.; Viola, P.

    2005-02-01

    An approach to verify the intensity modulated radiation therapy (IMRT) using an anthropomorphic phantom is reported. Step and shoot IMRT was delivered to a Rando phantom and the portal dose computed by a treatment planning system (TPS) was verified by a linear array of liquid ion-chambers. The array was calibrated in terms of dose to water, and supplies dose profiles with a spatial resolution of 1mm. In general the comparison between the experimental portal dose profiles and those computed by the TPS, is needed to detect the inaccuracy sources as the approximation of the calculation algorithms, patient positioning, linac mechanical failures as the incorrect sequences of segment beams. Using a Rando phantom the accuracy level of the TPS algorithm that supplies the portal dose was determined by the γ-index.

  17. Sodium-glucose co-transporter-2 inhibitors as add-on therapy to insulin: rationale and evidences.

    PubMed

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    Sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are recently approved class of anti-hyperglycaemic agents for the treatment of type 2 diabetes mellitus (T2DM). SGLT-2I inhibits renal glucose reabsorption, thereby ensuing urinary glucose excretion in a dose-dependent manner. This caloric loss and osmotic diuresis, secondary to increased urinary glucose excretion, has a unique potential to counter insulin induced weight gain and fluid retention, with little potential of hypoglycemic exacerbation. Also, as these agents act independently of insulin secretion or action, they are effective even in long-standing diabetes with depleted β-cell reserve. Improvement in insulin sensitivity, as observed with SGLT-2I can also facilitate insulin action. Furthermore, significant reduction in total daily insulin dosage and reduction of body weight as observed during combination therapy renders SGLT-2I, a near-ideal partner to insulin. This review aims to evaluate the safety and efficacy of currently used SGLT-2I as an add-on to insulin therapy in the treatment of T2DM. PMID:26732230

  18. The Influence of Insulin Therapy on the Course of Acute Exacerbation of Bronchial Asthma.

    PubMed

    Wytrychowski, K; Obojski, A; Hans-Wytrychowska, A

    2016-01-01

    Large doses of systemic corticosteroids are the basis of treatment of acute exacerbation of bronchial asthma. The hyperglycemic activity of systemic corticosteroids often leads to the loss of control of diabetes diagnosed earlier or to its first diagnosis during treatment of the exacerbation of asthma. We conducted a prospective, randomized study in a group of 24 adult patients treated for asthma exacerbation, with the blood glucose level at admission above 8.4 mmol/l. The patients were randomly divided into a group treated with intravenous insulin infusion by an electric syringe pump in doses controlling glycemia at 4.5-7.2 mmol/l (Group A) and a group of patients treated with insulin administered subcutaneously in three doses controlling glycemia at 7.2-10.0 mmol/l (Group B). A control group (Group C) consisted of patients without any disturbances in carbohydrate metabolism, treated for exacerbation of asthma. Asthma exacerbation was treated in all groups in a uniform way. We found that the average hospitalization time was 8.2 ± 2.4 days in Group A, 10.2 ± 5.2 days in Group B, and 5.8 ± 1.9 days in Group C; the last being significantly shorter than those in Groups A and B. We conclude that hyperglycemia is a significant factor increasing the risk of extending hospitalization time due to asthma exacerbation, regardless of the way of insulin therapy. PMID:26453066

  19. Effects of Hormone Replacement Therapy on Insulin Resistance in Postmenopausal Diabetic Women

    PubMed Central

    Bitoska, Iskra; Krstevska, Branka; Milenkovic, Tatjana; Subeska-Stratrova, Slavica; Petrovski, Goran; Mishevska, Sasha Jovanovska; Ahmeti, Irfan; Todorova, Biljana

    2016-01-01

    BACKGROUND: Insulin resistance (IR) is closely associated with diabetes mellitus. On the other hand, increased visceral fat in menopause is also associated with IR, which makes postmenopausal diabetic women in a big risk for cardiovascular diseases. There are conflicting reports about the effects on hormone replacement therapy (HRT) on IR. AIM: The aim of the study was to investigate the effects of HRT on IR. METHODS: A total of 40 postmenopausal women with type 2 diabetes were enrolled and followed for 12 months. Half of them were assigned to take HRT, while the other half made the control group. Fasting plasma glucose (FPG) and insulinemia were measured in both groups at baseline and after 12 months. IR was represented by Homeostatic model assessment for IR (HOMA-IR). RESULTS: HRT was associated with significant decrease in HOMA-IR, FPG and insulinemia in the examined group. There was no significant reduction in FPG and no significant increase in insulinemia levels and HOMA-IR values in control group after 12 months. CONCLUSION: HRT was associated with statistically signifficant increase of insulin sensitivity. Larger clinical trials will be necessary to understand whether HRT may improve insulin resistance and glucose homeostasis in women with diabetes, especially when given shortly after entering menopause.

  20. Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy.

    PubMed

    Marshall, Merville C

    2007-08-01

    A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African-American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID:17722663

  1. Historical data enhances safety supervision system performance in T1DM insulin therapy risk management.

    PubMed

    Hughes-Karvetski, Colleen; Patek, Stephen D; Breton, Marc D; Kovatchev, Boris P

    2013-02-01

    Safety measures to prevent or mitigate hypoglycemia are an important component of open loop, closed loop, and advisory mode insulin therapy control settings in type 1 diabetes. In recent work, we introduce a method for the automatic, gradual attenuation of the insulin pump delivery rate when a risk of hypoglycemia is detected, a method that we refer to as brakes. In the methods presented here, we demonstrate the use of historical glucose measurement data to inform and enhance the ability of the brakes to prevent hypoglycemia in real-time. The updated brakes are based on a patient-specific, time-varying model that reflects the typical trajectory of glycemic fluctuations throughout the day. Historical heightened risk of hypoglycemia throughout the day prompts an increase in the aggressiveness of insulin attenuation as compared to the original brakes that are based on real-time data alone. Through the use of available real-time data supplemented with historical glucose information to assess hypoglycemic risk, we are able to better anticipate and prevent hypoglycemia. PMID:22342221

  2. Intensification of insulin therapy in patients with type 2 diabetes: a retrospective, non- interventional cohort study of patients treated with insulin glargine or biphasic human insulin in daily clinical practice

    PubMed Central

    2013-01-01

    Background The aim of this study is to compare the efficacy of intensification of insulin treatment with insulin glargine and biphasic human insulin in patients with type 2 diabetes on concomitant therapy with oral antidiabetic drugs (OAD) in daily clinical practice. Methods A retrospective multicentre parallel two-arm study included 301 patients with type 2 diabetes already on treatment with biphasic human insulin twice daily (bd) in combination with OAD. Data were collected retrospectively from 142 patients who had been switched from biphasic human insulin to insulin glargine in a period of 6–12 months prior to their inclusion (active group) and compared to data collected retrospectively from 159 patients who continued treatment with biphasic human insulin bd for the same time period (control group). Our primary objective was to examine the efficacy of the two treatments, assessed as change in HbA1c. Secondary objectives were to examine for changes in fasting blood glucose (FBG), body weight, treatment with OAD or fast-acting insulin and safety, by assessing the frequency and severity of hypoglycaemic episodes. Results At the end of the study there was a significant reduction in HbA1c in both arms. The least squares (LS) mean [(95% confidence intervals (CI)] reduction in HbA1c was -1.13 (-0.96 to -1.30)% in the active and -0.59 (-0.41to -0.77)% in the control group [LS mean treatment difference 0.53 (0.31-0.76)%, p < 0.001]. Similarly, fasting blood glucose declined significantly in both arms. The LS mean decline in FBG was -47.02 (-37.89 to -56.14) mg/dl in the active and -19.73 (-11.57 to -27.89) mg/dl in the control group [LS mean treatment difference 27.85 (15.74-39.95) mg/dl, p < 0.001]. No significant difference in hypoglycaemic episodes and in body weight was found. In the active group, more patients received rapid-acting pre-meal insulin and used insulin secretagogues drugs. Conclusions Glargine alone or in combination with fast acting insulin

  3. Low Intensity Laser Therapy Applied in the Healing of Wounds

    NASA Astrophysics Data System (ADS)

    Kahn, Fred; Matthews, Jeffrey

    2009-06-01

    Objective: The aim of this study was to determine the outcomes of Low Intensity Laser Therapy (LILT) on wound healing for patients presenting with pain, compromised neurological and physical function and tissue damage associated with vascular/diabetic ulcerations of the lower extremity. Methods: A retrospective case review of six patients treated with LILT (GaAlAs SLD, 660 nm, 750 mW, 3.6 J/cm2; GaAlAs SLD, 840 nm, 1,500 mW, 6.48 J/cm2; GaAlAs laser, 830 nm, 75 mW, 270 J/cm2) was conducted of clinical features including pain, measured by visual analogue scale (VAS), motor function, measured by range of motion (ROM) and visual outcome, measured by wound dimensions for six patients (n = 6; 5 males, 1 female; age = 67.83 years). Results: Significant progress with regard to alleviation of pain (ΔVAS = -5), improvements in motor function (ΔROM = +40%), epithelialization (wound closure rate = 3%/week) and complete wound closure was achieved. No recurrence of pathology at least one month post cessation of therapy was evident (x¯% reduction in wound area = 100%). Conclusions: LILT achieved consistent, effective and clear endpoints, was cost effective, created no adverse effects and ultimately led to the salvage of extremities.

  4. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  5. Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

    PubMed Central

    Vanikar, A. V.; Dave, S. D.; Thakkar, U. G.; Trivedi, H. L.

    2010-01-01

    Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4) patients with 1–24-year disease duration, in age group: 13–43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 103/μL, CD45−/90+/73+:40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1 × 103/μL, CD45−/34+:0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques. PMID:21197448

  6. High Reported Treatment Satisfaction in People With Type 1 Diabetes Switching to Latest Generation Insulin Pump Regardless of Previous Therapy

    PubMed Central

    Barnard, Katharine D; Bromba, Michael; de Lange, Mirja; Halbron, Marine; Levy, Brian L.; Lévy, Marc; Lippmann-Grob, Bernhard; Walshe, Kieran; Ziegler, Ralph

    2015-01-01

    Background: The effects of transition by individuals with type 1 diabetes (T1D) to more recently available continuous glucose monitoring (CGM)-enabled insulin pumps from either multiple daily insulin injections (MDI) or older insulin pumps on treatment satisfaction have not been well studied. We conducted a survey to assess treatment satisfaction among users of the Animas® Vibe™ insulin pump, a latest generation insulin pump (LGIP) system (CGM-enabled), after switching from MDI or earlier generation insulin pumps. Methods: Individuals with T1D from 141 centers in 5 countries and 4 language areas participated in the survey. Treatment satisfaction was assessed by the Insulin Treatment Satisfaction Questionnaire (ITSQ), which was included in a 50-item online questionnaire that also assessed preference for using the LGIP compared with previous treatment and satisfaction with key LGIP features. Results: A total of 356 individuals, ages 12-79 years, responded to the survey: mean (SD) age 38.4 (16.1) years; diabetes duration 19.1 (13.3) years; female 59%; previously treated with MDI 58%. Overall mean (SD) ITSQ scores were high among all respondents regardless of prior treatment: 95.1 (23.2) (scale: 0-132). No differences between previous-treatment groups were seen. Most (83%) of respondents rated the LGIP to be better than their previous insulin delivery system: “much better” (65%), “a bit better” (18%) regardless of age, and 95% would recommend using the LGIP to others. Conclusions: Use of the Animas Vibe was associated with high treatment satisfaction and perceived as a better method of insulin delivery regardless of previous insulin therapy or age. PMID:25591855

  7. Continuous subcutaneous insulin infusion: practical issues

    PubMed Central

    Saboo, Banshi D.; Talaviya, Praful A.

    2012-01-01

    The growing number of individuals with diabetes mellitus has prompted new way of treating these patients, continuous subcutaneous insulin infusion (CSII) or insulin pump therapy is an increasingly form of intensive insulin therapy. An increasing number of individuals with diabetes mellitus individuals of all ages have started using insulin pump therapy. Not everyone is a good candidate for insulin pump therapy, and the clinician needs to be able to determine which patients are able to master the techniques required and to watch for the adverse reactions that may develop. Insulin pump increases quality of life of patient with diabetes mellitus with increasing satisfaction with treatment and decrease impact of diabetes mellitus. Manual errors by insulin pump users may lead to hypo or hyperglycemia, resulting into diabetic ketoacidosis (DKA) sometimes. Some of practical aspect is associated with insulin pump therapy such as selection of candidates, handling of pump and selection of site, and pump setting, henceforth this review is prepared to explore and solve the practical problems or issues associated with pump therapy. PMID:23565394

  8. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  9. Ultrasound-based guidance of intensity-modulated radiation therapy

    SciTech Connect

    Fung, Albert Y.C. . E-mail: afung@unmc.edu; Ayyangar, Komanduri M.; Djajaputra, David; Nehru, Ramasamy M.; Enke, Charles A.

    2006-04-01

    In ultrasound-guided intensity-modulated radiation therapy (IMRT) of prostate cancer, ultrasound imaging ascertains the anatomical position of patients during x-ray therapy delivery. The ultrasound transducers are made of piezoelectric ceramics. The same crystal is used for both ultrasound production and reception. Three-dimensional (3D) ultrasound devices capture and correlate series of 2-dimensional (2D) B-mode images. The transducers are often arranged in a convex array for focusing. Lower frequency reaches greater depth, but results in low resolution. For clear image, some gel is usually applied between the probe and the skin contact surface. For prostate positioning, axial and sagittal scans are performed, and the volume contours from computed tomography (CT) planning are superimposed on the ultrasound images obtained before radiation delivery at the linear accelerator. The planning volumes are then overlaid on the ultrasound images and adjusted until they match. The computer automatically deduces the offset necessary to move the patient so that the treatment area is in the correct location. The couch is translated as needed. The currently available commercial equipment can attain a positional accuracy of 1-2 mm. Commercial manufacturer designs differ in the detection of probe coordinates relative to the isocenter. Some use a position-sensing robotic arm, while others have infrared light-emitting diodes or pattern-recognition software with charge-couple-device cameras. Commissioning includes testing of image quality and positional accuracy. Ultrasound is mainly used in prostate positioning. Data for 7825 daily fractions of 234 prostate patients indicated average 3D inter-fractional displacement of about 7.8 mm. There was no perceivable trend of shift over time. Scatter plots showed slight prevalence toward superior-posterior directions. Uncertainties of ultrasound guidance included tissue inhomogeneities, speckle noise, probe pressure, and inter

  10. Preoperative Intensity Modulated Radiation Therapy for Retroperitoneal Sarcoma

    PubMed Central

    El-Bared, Nancy; Taussky, Daniel; Mehiri, Selma; Patocskai, Erika; Roberge, David; Donath, David

    2014-01-01

    The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <5 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p = 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered. PMID:23919397

  11. Approaching oxygen-guided intensity-modulated radiation therapy

    PubMed Central

    Epel, Boris; Redler, Gage; Pelizzari, Charles; Tormyshev, Victor M.; Halpern, Howard J.

    2016-01-01

    The outcome of cancer radiation treatment is strongly correlated with tumor oxygenation. The aim of this study is to use oxygen tension distributions in tumors obtained using Electron Paramagnetic Resonance (EPR) imaging to devise better tumor radiation treatment. The proposed radiation plan is delivered in two steps. In the first step, a uniform 50% tumor control dose (TCD50) is delivered to the whole tumor. For the second step an additional dose boost is delivered to radioresistant, hypoxic tumor regions. FSa fibrosarcomas grown in the gastrocnemius of the legs of C3H mice were used. Oxygen tension images were obtained using a 250 MHz pulse imager and injectable partially deuterated trityl OX63 (OX71) spin probe. Radiation was delivered with a novel animal intensity modulated radiation therapy (IMRT) XRAD225Cx microCT/radiation therapy delivery system. In a simplified scheme for boost dose delivery, the boost area is approximated by a sphere, whose radius and position are determined using an EPR O2 image. The sphere that irradiates the largest fraction of hypoxic voxels in the tumor was chosen using an algorithm based on Receiver Operator Characteristic (ROC) analysis. We used the fraction of irradiated hypoxic volume as the true positive determinant and the fraction of irradiated normoxic volume as the false positive determinant in the terms of that analysis. The most efficient treatment is the one that demonstrates the shortest distance from the ROC curve to the upper left corner of the ROC plot. The boost dose corresponds to the difference between TCD90 and TCD50 values. For the control experiment an identical radiation dose to the normoxic tumor area is delivered. PMID:26782211

  12. Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

    SciTech Connect

    Lim, Karen; Stewart, James; Kelly, Valerie; Xie, Jason; Brock, Kristy K.; Moseley, Joanne; Cho, Young-Bin; Fyles, Anthony; Lundin, Anna; Rehbinder, Henrik; Löf, Johan; Jaffray, David A.; Milosevic, Michael

    2014-09-01

    Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

  13. Preoperative intensity modulated radiation therapy for retroperitoneal sarcoma.

    PubMed

    El-Bared, Nancy; Taussky, Daniel; Mehiri, Selma; Patocskai, Erika; Roberge, David; Donath, David

    2014-06-01

    The use of intensity modulated radiation therapy (IMRT) has allowed for the administration of high doses to retroperitoneal sarcomas (RSTS) while limiting toxicity to adjacent organs. The purpose of our study is to assess the outcome and toxicities of patients with RSTS treated with neo-adjuvant external beam radiation (EBRT) therapy using IMRT. This is a retrospective study of 21 patients treated with preoperative IMRT for primary or recurrent RSTS between 2005 and 2011. Overall survival (OS) and local recurrence free survival (LRFS) were computed using the Kaplan-Meier method (log-rank test). Acute and chronic toxicities were assessed using the CTCAE v. 3 criteria. The actuarial 2 and 3-year OS was 66% for both and the 5-year OS was 51%. As for LRFS it was 57% at 2 and 3-year and 51% for the 5-year LRFS. Factors predictive for local control were microscopically negative margins (p = 0.022), a median tumor diameter <15 cm (p = 0.007) and pathology of liposarcoma (p = 0.021). Furthermore, patients treated for recurrent disease fared worse (p = 0.04) in local control than patients treated for primary disease. As for OS, patients treated for Grade 1 histology had a better outcome (p 5 0.05). EBRT was generally well tolerated. Acute gastrointestinal (GI) Grade 1 or 2 toxicities occurred in 33% of patients and one patient had unexplained post-radiation Grade 2 fever that resolved after tumor resection. As for chronic toxicities 24% of our patients presented Grade 1 GI toxicity and one patient presented Grade 3 small bowel stenosis not clearly due to radiation toxicity. Despite the location and volume of the tumors treated, preoperative IMRT was very well tolerated in our patients with retroperitoneal sarcoma. Unfortunately local recurrences remain common and dose escalation is to be considered. PMID:23919397

  14. Non-insulin antidiabetic therapy in cardiac patients: current problems and future prospects.

    PubMed

    Fisman, Enrique Z; Motro, Michael; Tenenbaum, Alexander

    2008-01-01

    ) these hazards are not mere 'side effects' but are deeply rooted in the drugs' mechanisms of action; (3) current data indicate that combined glibenclamide/metformin therapy seems to present a special risk and should be avoided in the long-term management of type 2 diabetics with proven CAD, and (4) Non-Insulin Antidiabetic Therapy in Diabetic Cardiac Patients 155 customized antihyperglycemic pharmacological approaches should be investigated for the optimal treatment of diabetic patients with heart disease. New possibilities are represented by incretin mimetic compounds, dipeptidyl peptidase (DPP)-4 inhibitors, inhaled insulin and eventually oral insulin. PMID:18230961

  15. High Intensity Laser Therapy (HILT) versus TENS and NSAIDs in low back pain: clinical study

    NASA Astrophysics Data System (ADS)

    Zati, Allesandro; Fortuna, Damiano; Valent, A.; Filippi, M. V.; Bilotta, Teresa W.

    2004-09-01

    Low back pain, caused by lumbar disc herniation, is prevalently treated with a conservative approach. In this study we valued the efficacy of High Intensity Laser Therapy (HILT), compared with accepted therapies such as TENS and NSAIDs. Laser therapy obtained similar results in the short term, but better clinical effect over time than TENS and NSAIDs. In conclusion high intensity laser therapy appears to be a interesting new treatment, worthy of further research.

  16. Type 1 Diabetes Patients Using Continuous Subcutaneous Insulin Infusion Therapy: Feeling Burdened Correlated with Factors

    PubMed Central

    Nishio, Ikuko; Chujo, Masami

    2015-01-01

    Background The purpose of this study was to investigate factors related to feelings of being burdened in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII) therapy. Methods Participants were 106 subscribers to the Diabetes Network’s e-mail newsletter. An online survey was used. Eligible participants were aged at least 20 years, had type 1 diabetes, and were using CSII. Survey questions concerned whether participants found CSII burdensome, and seven potential reasons for feelings of burden. Analysis calculated correlations among participants’ demographic and treatment-related factors, and among participants’ reasons for feeling CSII to be burdensome. Results Regarding demographic and treatment-related factors, gender was found to be weakly negatively correlated with the following variables: employment status, and whether participants had discussed their concerns with a doctor. Employment status was found to be weakly correlated with diabetes duration; employment status and diabetes duration were found to be weakly correlated with age. Regarding reasons for finding CSII therapy burdensome, “It takes too much time” was found to be strongly positively correlated with “It interferes with work responsibilities”; 16 weak positive correlations were also found. Conclusion To explain our results, we suggest that medical expenses, glycemic control, scheduling outpatient visits around home and work responsibilities, and interacting with medical staff may have caused participants to find CSII therapy burdensome. Most participants had never discussed their treatment concerns with a doctor. This suggests that nurses may be able to mitigate feeling burdened in participants using CSII therapy. PMID:26538798

  17. Clinical Experience with Insulin Glargine in Type 1 Diabetes

    PubMed Central

    Moser, Emily; Dain, Marie-Paule; Rodionova, Anastasia

    2010-01-01

    Abstract The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal–bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults. PMID:20969435

  18. Reshapable physical modulator for intensity modulated radiation therapy.

    PubMed

    Xu, Tong; Shikhaliev, Polad M; Al-Ghazi, Muthana; Molloi, Sabee

    2002-10-01

    A new method of generating beam intensity modulation filters for intensity modulated radiation therapy (IMRT) is presented. The modulator was based on a reshapable material, which is not compressible but can be deformed under pressure. A two-dimensional (2D) piston array was used to repeatedly shape the attenuating material. The material is a mixture of tungsten powder and a silicon-based binder. The linear attenuation coefficient of the material was measured to be 0.409 cm(-1) for a 6 MV x-ray beam. The maximum thickness of the physical modulator is 10.2 cm, allowing a transmission of 1.5%. A 16 x 16 square piston array was used to generate a depth pattern in the deformable attenuating material. Each piston has a cross section of 6.37 x 6.37 mm2. The modulator was placed 65 cm from the radiation source of the linear accelerator in the position of the shielding tray. At this position, each piston projects to a 1.0 x 1.0 cm2 area at the isocenter, giving a treatment field of 16 x 16 cm2. The percent depth dose curve and output factor measurement show a slight beam hardening and a 1%-4% increase in scatter fraction when 2.2-4.4 cm uniform thickness filters are in the beam. The surface dose was decreased with the filter in the beam. Ion chamber and verification films were used to verify the entrance dose. The measured absolute and relative doses were compared with the calculated dose. The agreement of measurements and calculations is within 3%. In order to verify the spatial modulation of dose, 1-D dose profiles were obtained using dose calculations. Calculated and measured profiles were compared. The 20%-80% penumbra of the modulator was measured to be 5.5-10 mm. The results show that a physical modulator formed using a 16 x 16 piston array and a deformable attenuation material can provide intensity modulation for IMRT comparable with those provided by currently available commercial MLC techniques. PMID:12408295

  19. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

    2000-11-01

    A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

  20. [Factors limiting glycaemic control in insulin-treated type 2 diabetes].

    PubMed

    Ferencz, Viktória; Domján, Beatrix; Gerő, László; Tänczer, Tímea; Tabák, Gy Ádám

    2015-09-01

    Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia. PMID:26320598

  1. Failure to initiate early insulin therapy – A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35)

    PubMed Central

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-01-01

    Context: Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). Aim: The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Materials and Methods: Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Results: Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02–1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). Conclusions: The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control. PMID:27488152

  2. The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

    PubMed

    Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

    2015-11-01

    The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. PMID:26481101

  3. Diabetes and Insulin Therapy, but Not Metformin, Are Related to Hepatocellular Cancer Risk

    PubMed Central

    Bosetti, Cristina; Rapaccini, Gianlodovico; Gasbarrini, Antonio; La Vecchia, Carlo; Boccia, Stefania; Grieco, Antonio

    2015-01-01

    Introduction. Metabolic conditions, including type 2 diabetes, have been related to hepatocellular carcinoma (HCC) risk. We have further analyzed the role of diabetes and antidiabetic treatments on HCC. Methods. Data derived from a hospital-based case-control study (Italy, 2005–2012) on 224 HCC patients and 389 controls. Odds ratios (ORs) were estimated using multiple logistic regression models. Results. Sixty-nine (30.9%) cases versus 52 (13.5%) controls reported a diabetes diagnosis, corresponding to a multivariate OR of 2.25 (95% confidence interval, CI = 1.42–3.56). A stronger excess risk emerged for a longer time since diabetes diagnosis (OR = 2.96 for <10 years and 5.33 for ≥10 years). Oral therapies were inversely, though not significantly, related to HCC risk, OR being 0.44 for metformin and 0.88 for sulfonylureas; conversely, insulin was nonsignificantly directly associated (OR = 1.90). Compared to nondiabetic subjects who were never smokers, those who were diabetics and ever smokers had an OR of 6.61 (95% CI 3.31–13.25). Conclusion. Our study confirms an over 2-fold excess HCC risk in diabetics, with a stronger excess risk in diabetic subjects who are also tobacco smokers. Metformin may decrease the risk of HCC, whereas insulin may increase the risk. PMID:26074956

  4. Basal insulin analogs: from pathophysiology to therapy. What we see, know, and try to comprehend?

    PubMed

    Monnier, L; Colette, C; Owens, D

    2013-12-01

    During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable. PMID:24139826

  5. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    PubMed

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy. PMID:25597225

  6. Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

    PubMed Central

    Brahmkhatri, Varsha P.; Prasanna, Chinmayi; Atreya, Hanudatta S.

    2015-01-01

    Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies. PMID:25866791

  7. Skeletal effects of growth hormone and insulin-like growth factor-I therapy.

    PubMed

    Lindsey, Richard C; Mohan, Subburaman

    2016-09-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis. PMID:26408965

  8. AB067. Future ED therapy: low-energy shock wave therapy and low-intensity pulsed ultrasound therapy

    PubMed Central

    Xin, Zhong-Cheng

    2015-01-01

    Current treatments for erectile dysfunction (ED) such as phosphodiesterase type 5 inhibitors (PDE5Is) and intracavernosal injections (ICI) therapy, such a symptom therapy used as on demanded before sexual intercourse, the clinical efficacy reached to 80%, with mild side effects, however, such a symptom therapy could not restore pathological changes in the penis. Low-energy shock wave therapy (LESWT) has been developed for treating ED, and clinical studies have shown that LESWT has the potential to affect PDE5I non-responders with ED with few adverse effects. Studies have reported that LESWT could partially restore corpus cavernosum fibromuscular pathological changes, include corpus cavernosum smooth muscle and endothelial dysfunction, and neuropathy. Although the mechanisms remain to be further investigated its underlying mechanisms may involve recruiting endogenous mesenchymal stem cells. Recently, device of low-intensity pulsed ultrasound (LIPUS) has been developed and animal study had been proven to have effects of improving erectile function and restoring pathological changes in penile tissue in STZ-induced diabetic ED, however, it is needed to perform clinical study. LESWT & LIPUS could be novel therapy for treating ED with restore pathological changes in the penis in the near future. However, further extensive evidence-based basic and clinical studies are needed.

  9. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  10. Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

    SciTech Connect

    Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

    2012-11-01

    Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

  11. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  12. Emerging technology in diabetes mellitus: glucose monitoring and new insulins.

    PubMed

    Reynolds, L Raymond; Karounos, Dennis G

    2002-08-01

    Modern diabetes management requires intensive self-monitoring of blood glucose levels, often coupled with a multicomponent insulin program. Recent advances include alternate site blood glucose testing devices, which facilitate more frequent sampling by individuals with diabetes. Continuous glucose monitoring through interstitial fluid analysis is now available and appears to give a more representative picture of the glycemic variations typical for type 1 diabetes. Recombinant DNA technology has led to the development of new insulin analogs that provide more physiologic insulin delivery. Inhaled and oral insulin formulations may replace multiple injections in future insulin therapy regimens. PMID:12190231

  13. Comparative analysis of 60Co intensity-modulated radiation therapy.

    PubMed

    Fox, Christopher; Romeijn, H Edwin; Lynch, Bart; Men, Chunhua; Aleman, Dionne M; Dempsey, James F

    2008-06-21

    In this study, we perform a scientific comparative analysis of using (60)Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and (60)Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered (60)Co beams and (iii) a helical tomotherapy (60)Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and (60)Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant (60)Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical (60)Co beam geometry achieved similar plan quality as static plans with 11 equidistant (60)Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and (60)Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable

  14. [Anesthesia and intensive therapy for a patient with mitochondrial myopathy].

    PubMed

    Breucking, E; Mortier, W; Lampert, R; Brandt, L

    1993-10-01

    Since 1983 we have been involved in the diagnostic work-up and emergency treatment of a female patient now 48 years old who has a mitochondrial myopathy resembling Luft's disease. The syndrome was first described in 1959, and in more detail in 1962, by Luft and et al., who reported a picture of hypermetabolism with high temperature, extreme sweating, tachycardia, dyspnoea at rest, polydipsia, polyphagia and irritability but normal thyroid function. In 1971 and 1976 Haydar and Di Mauro presented a second case and proposed treatment with chloramphenicol. Our patient has the third case of the syndrome reported so far: her case was initially published in 1987. CASE REPORT. Since her 17th year of life the patient had suffered from episodes of fever, tachycardia and sweating. At the age of 32 these attacks worsened, leading to unconsciousness and apnoea. The patient then had to be intubated, ventilated and sometimes resuscitated. The diagnosis of MH susceptibility and Luft's disease was made on biochemical grounds after the first muscle biopsy in 1983. Therapy with chloramphenicol failed. Therapy with beta blockers, vitamin C and K or E, coenzyme Q10 and a high-caloric diet was started in 1985. The patient was registered with an emergency service, which flew her to our ICU whenever she had a severe crisis. For milder episodes she was supplied with an oxygen breathing mask at home. Myalgia increased with the episodes starting in 1988, and the patient needed dantrolene infusions and analgesics at home. To facilitate venepuncture a Port-A-Cath system was implanted in 1987, which had to be removed four times due to infection and sepsis. A muscle biopsy was taken in Rotterdam, which revealed differences in mitochondrial function from the biochemical findings recorded in 1983 and not in keeping with Luft's disease. Unfortunately, the patient was not able to undergo further metabolic investigations or therapeutic trials. ANAESTHESIA. The patient received three local and six

  15. Comparative analysis of 60Co intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Fox, Christopher; Romeijn, H. Edwin; Lynch, Bart; Men, Chunhua; Aleman, Dionne M.; Dempsey, James F.

    2008-06-01

    In this study, we perform a scientific comparative analysis of using 60Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and 60Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered 60Co beams and (iii) a helical tomotherapy 60Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and 60Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant 60Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical 60Co beam geometry achieved similar plan quality as static plans with 11 equidistant 60Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and 60Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable target coverage

  16. Insulin-dependent (type I) diabetes mellitus.

    PubMed Central

    Rodger, W

    1991-01-01

    Insulin-dependent (type I) diabetes mellitus is a chronic disease characterized by hyperglycemia, impaired metabolism and storage of important nutrients, evidence of autoimmunity, and long-term vascular and neurologic complications. Insulin secretory function is limited. Cell membrane binding is not primarily involved. The goal of treatment is to relieve symptoms and to achieve blood glucose levels as close to normal as possible without severe hypoglycemia. However, even with education and self-monitoring of the blood glucose level, attaining recommended target values (plasma glucose level less than 8.0 mmol/L before main meals for adults) remains difficult. Human insulin offers no advantage in glycemic control but is important in the management and prevention of immune-related clinical problems (e.g., injection-site lipoatrophy, insulin resistance and allergy) associated with the use of beef or pork insulin. Therapy with one or two injections per day of mixed short-acting or intermediate-acting insulin preparations is a compromise between convenience and the potential for achieving target plasma glucose levels. Intensive insulin therapy with multiple daily injections or continuous infusion with an insulin pump improves mean glycated hemoglobin levels; however, it increases rates of severe hypoglycemia and has not been shown to decrease the incidence of clinically significant renal, retinal or neurologic dysfunction. Future prospects include automated techniques of insulin delivery, immunosuppression to preserve endogenous insulin secretion and islet transplantation. PMID:1933705

  17. Inverse planning optimization method for intensity modulated radiation therapy.

    PubMed

    Lan, Yihua; Ren, Haozheng; Li, Cunhua; Min, Zhifang; Wan, Jinxin; Ma, Jianxin; Hung, Chih-Cheng

    2013-10-01

    In order to facilitate the leaf sequencing process in intensity modulated radiation therapy (IMRT), and design of a practical leaf sequencing algorithm, it is an important issue to smooth the planned fluence maps. The objective is to achieve both high-efficiency and high-precision dose delivering by considering characteristics of leaf sequencing process. The key factor which affects total number of monitor units for the leaf sequencing optimization process is the max flow value of the digraph which formulated from the fluence maps. Therefore, we believe that one strategy for compromising dose conformity and total number of monitor units in dose delivery is to balance the dose distribution function and the max flow value mentioned above. However, there are too many paths in the digraph, and we don't know the flow value of which path is the maximum. The maximum flow value among the horizontal paths was selected and used in the objective function of the fluence map optimization to formulate the model. The model is a traditional linear constrained quadratic optimization model which can be solved by interior point method easily. We believe that the smoothed maps from this model are more suitable for leaf sequencing optimization process than other smoothing models. A clinical head-neck case and a prostate case were tested and compared using our proposed model and the smoothing model which is based on the minimization of total variance. The optimization results with the same level of total number of monitor units (TNMU) show that the fluence maps obtained from our model have much better dose performance for the target/non-target region than the maps from total variance based on the smoothing model. This indicates that our model achieves better dose distribution when the algorithm suppresses the TNMU at the same level. Although we have just used the max flow value of the horizontal paths in the diagraph in the objective function, a good balance has been achieved between

  18. Survey of resident education in intensity-modulated radiation therapy.

    PubMed

    Malik, Renuka; Oh, Julia L; Roeske, John C; Mundt, Arno J

    2005-06-01

    Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States. Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education. Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (> or = 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated > 25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively. Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics

  19. IMRT (intensity modulated radiation therapy): progress in technology and reimbursement.

    PubMed

    Young, R; Snyder, B

    2001-01-01

    For a new treatment technology to become widely accepted in today's healthcare environment, the technology must not only be effective but also financially viable. Intensity modulated radiation therapy (IMRT), a technology that enables radiation oncologists to precisely target and attack cancerous tumors with higher doses of radiation using strategically positioned beams while minimizing collateral damage to healthy cells, now meets both criteria. With IMRT, radiation oncologists for the first time have obtained the ability to divide the treatment field covered by each beam angle into hundreds of segments as small as 2.5 mm by 5 mm. Using the adjustable leaves of an MLC to shape the beam and by controlling exposure times, physicians can deliver a different dose to each segment and therefore modulate dose intensity across the entire treatment field. Development of optimal IMRT plans using conventional manual treatment planning methods would take days. To be clinically practical, IMRT required the development of "inverse treatment planning" software. With this software, a radiation oncologist can prescribe the ideal radiation dose for a specific tumor as well as maximum dose limits for surrounding healthy tissue. These numbers are entered into the treatment planning program which then calculates the optimal delivery approach that will best fit the oncologist's requirements. The radiation oncologist then reviews and approves the proposed treatment plan before it is initiated. The most recent advance in IMRT technology offers a "dynamic" mode or "sliding window" technique. In this more rapid delivery method, the beam remains on while the leaves of the collimator continually re-shape and move the beam aperture over the planned treatment area. This creates a moving beam that saturates the tumor volume with the desired radiation dose while leaving the surrounding healthy tissue in a protective shadow created by the leaves of the collimator. In the dynamic mode, an IMRT

  20. [MODERN VIEW ON INTENSIVE THERAPY OF GASTRO-INTESTINAL HEMORRHAGE].

    PubMed

    Tutchenko, M I; Rudyk, D V; Iskra, N I; Trofimenko, S P; Shchur, I V

    2015-10-01

    Basing on analysis of the treatment results in 47 patients for gastro-intestinal hemorrhage, the experience of application of a tranexamic acid in a content of infusion therapy and hemaxam per os was adduced. The data obtained witness the expediency of hemaxam application in a content of therapy on the stage of a hemorrhage letup and for the recurrence prevention. PMID:26946650

  1. Low-intensity voluntary running lowers blood pressure with simultaneous improvement in endothelium-dependent vasodilatation and insulin sensitivity in aged spontaneously hypertensive rats.

    PubMed

    Sun, Meng-Wei; Qian, Feng-Lei; Wang, Jian; Tao, Tao; Guo, Jing; Wang, Lie; Lu, Ai-Yun; Chen, Hong

    2008-03-01

    Our objective is to examine the effects of voluntary running at different intensity levels on blood pressure, endothelium-dependent vessel dysfunction and insulin resistance in aged spontaneously hypertensive rats (SHR) with severe hypertension. Ten-month-old male and female SHR with severe hypertension were assigned to voluntary running at either low intensity (30% of maximal aerobic velocity) or moderate intensity (60% of maximal aerobic velocity) on a motor-driven treadmill for 6 weeks, 20 min per day and 7 days per week. Age-matched Wistar-Kyoto rats and SHR were kept under sedentary conditions as controls. Blood pressure and heart rate were measured by the tail-cuff method. At the end of the exercise training, blood samples were collected for glucose, insulin and lipids assay, and aortae were isolated to examine their function in vitro. Low-intensity but not moderate-intensity running significantly lowered blood pressure in both male and female SHR (p<0.01). There was significant impairment in acetylcholine-induced vasorelaxation in SHR (p<0.01), which was improved by low-intensity training (p<0.05). Nitric oxide synthase blockade abrogated the improvement in endothelium-dependent relaxation. Hypertensive rats had elevated blood glucose and insulin levels with lowered insulin sensitivity that was ameliorated by low-intensity running. A significant increase in blood high-density lipoprotein (HDL)-cholesterol and a significant decrease in triglycerides were found in exercised SHR. In conclusion, low-intensity voluntary exercise lowers hypertension in aged SHR with severe hypertension. Exercise-induced simultaneous improvement in endothelium-dependent vessel relaxation and insulin sensitivity may act concomitantly in attenuating cardiovascular risk factors in aged hypertensive rats with significantly high blood pressure. PMID:18497475

  2. Short communication: The relationship between mitochondrial dysfunction and insulin resistance in HIV-infected children receiving antiretroviral therapy.

    PubMed

    Sharma, Tanvi S; Jacobson, Denise L; Anderson, Lynn; Gerschenson, Mariana; Van Dyke, Russell B; McFarland, Elizabeth J; Miller, Tracie L

    2013-09-01

    Mitochondrial abnormalities may lead to metabolic complications in HIV-infected children who have been receiving long-term antiretroviral treatment. We conducted a matched, case-control study comparing 21 HIV-infected children with insulin resistance (cases) to 21 HIV-infected children without insulin resistance (controls) to assess differences in mitochondrial DNA (mtDNA) copies/cell and oxidative phosphorylation NADH dehydrogenase (C1) and cytochrome c oxidase (C4) enzyme activities in peripheral blood mononuclear cells. MtDNA copies/cell tended to be lower in cases, and fasting serum glucose levels were inversely and significantly correlated with C1 enzyme activity, more so in cases. Larger pediatric studies should evaluate mitochondrial etiologies of insulin resistance and determine the role of antiretroviral therapies or HIV infection on mitochondrial dysfunction. PMID:23742635

  3. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

    PubMed

    Lee, Katrina; Lenards, Nishele; Holson, Janice

    2016-01-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. PMID:26235550

  4. Disordered Eating Behaviors in Youth with Type 1 Diabetes: Prospective Pilot Assessment Following Initiation of Insulin Pump Therapy

    PubMed Central

    Markowitz, Jessica T.; Alleyn, Cielo A.; Phillips, Roxanne; Muir, Andrew; Young-Hyman, Deborah

    2013-01-01

    Abstract Background There is risk for disordered eating behaviors in type 1 diabetes, especially related to insulin manipulation. Implementation of insulin pump therapy may encourage either normalization of eating behaviors or a greater focus on food intake due to renewed emphasis on carbohydrate counting. There is need for prospective studies to assess disordered eating behaviors upon implementation of pump therapy using diabetes-specific measurement tools. Subjects and Methods In a multicenter pilot study, 43 youth with type 1 diabetes, 10–17 years old, were assessed prior to pump initiation and after 1 and 6 months of pump therapy. Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a validated measure of risk for both diabetes-specific and general disordered eating behaviors. Results Youth (45% female), 13.3 years old with diabetes for 2.1 years, had a mean hemoglobin A1c of 8.3±1.3% (68±14.5 mmol/mol) at baseline. DEPS-R scores decreased over time (P=0.01). Overall rate of high risk for eating disorders was low. Overweight/obese youth endorsed more disordered eating behaviors than normal-weight participants. DEPS-R scores were correlated with z-score for body mass index at all three time points and with hemoglobin A1c after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6 months and was higher in overweight/obese compared with normal-weight participants. Conclusions Initiation of insulin pump therapy was associated with diminished endorsement of disordered eating behaviors in youth with type 1 diabetes. Longer follow-up studies are needed to assess the impact of insulin pump therapy on glycemic control, weight status, and disordered eating behaviors in this vulnerable population. PMID:23550556

  5. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study

    PubMed Central

    Cederholm, Jan; Eliasson, Björn; Rawshani, Araz; Eeg-Olofsson, Katarina; Svensson, Ann-Marie; Zethelius, Björn; Avdic, Tarik; Landin-Olsson, Mona; Jendle, Johan; Gudbjörnsdóttir, Soffia

    2015-01-01

    Objective To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Design Observational study. Setting Swedish National Diabetes Register, Sweden 2005-12. Participants 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. Main outcome measures Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. Results Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and

  6. Major Long-Term Benefits of Intensive Therapy for Type 1 Diabetes

    MedlinePlus

    ... Benefits of Intensive Therapy for Type 1 Diabetes: Study Reports Near-Normal Glucose Levels Lead to Large ... the latest results from a landmark government-sponsored study, reported at a special symposium held at the ...

  7. [Extracorporeal therapy of patients with liver disease in the intensive care unit].

    PubMed

    Fuhrmann, V; Horvatits, T; Drolz, A; Rutter, K

    2014-05-01

    Acute and acute-on-chronic liver failure are often associated with development of organ failure. Its occurrence is associated with high morbidity and mortality. Extracorporeal replacement therapies are frequently necessary in these patient populations. Replacement therapies can be divided into renal replacement therapies and liver support therapies. These therapies consist of artificial liver support systems (i.e., MARS(®) system, Prometheus(®)), which are able to remove water-soluble and albumin-bound toxins, and of bioartifical liver support systems. This manuscript provides a review of current practice in the extracorporeal support of patients with liver diseases in the intensive care unit. PMID:24770889

  8. Opinions and Satisfaction Regarding Continuous Subcutaneous Insulin Infusion Therapy in Adult Patients with Type 1 Diabetes

    PubMed Central

    Nishio, Ikuko; Chujo, Masami; Ohkura, Tsuyoshi; Kataoka, Hideyuki

    2015-01-01

    Background This study examined the treatment satisfaction of type 1 diabetic patients undergoing continuous subcutaneous insulin infusion (CSII) therapy, and patients’ thoughts regarding CSII. Methods We provided a self-administered questionnaire survey over the internet. Participants were 106 individuals with type-one diabetes aged 20 years or older, undergoing CSII. The survey examined patients’ treatment satisfaction, and their thoughts regarding CSII. Descriptive statistics were calculated. We compared relationships between treatment satisfaction and other variables using the Kruskal-Wallis rank sum test, and performed content analysis on participants’ thoughts regarding CSII. Results Regarding treatment satisfaction, the response, “neither of them” was the most frequent. Comparing relationships between treatment satisfaction and other variables, significant differences were found for the variables “age,” “presence of dissatisfaction regarding doctors’ response,” and “presence of a significant medical expense burden.” Participants’ thoughts regarding CSII were classified into 10 categories. Conclusion Participants expressed positive evaluations, such as that their blood sugar control had improved due to CSII, and that they perceived improvement in their health. Participants also expressed negative evaluations, however, such as that medical expenses resulting from CSII were high, and that these expenses may cause distress and future economic insecurity. In future, patients may benefit from nursing support that allows patients to confidently continue with CSII. PMID:26538796

  9. Insulin-like Growth Factor: Current Concepts and New Developments in Cancer Therapy

    PubMed Central

    King, Erin R.; Wong, Kwong-Kwok

    2013-01-01

    The insulin-like growth factor (IGF) family and the IGF-1 receptor (IGF-1R) play an important role in cancer. This intricate and complex signaling pathway provides many opportunities for therapeutic intervention, and several novel therapeutics aimed at the IGF-1R, particularly monoclonal antibodies and small molecule tyrosine kinase inhibitors, are under clinical investigation. This article provides a patent overview of the IGF signaling pathway and its complexity, addresses the justification for the use of IGF-1R-targeted therapy, and reviews the results of in vivo and in vitro novel therapeutics. Over the past year, the completion of several phase I, II, and III trials have provided interesting new information about the clinical activity of these novel compounds, particularly CP-751,871, IMC-A12, R1507, AMG-479, AVE-1642, MK-0646, XL-228, OSI-906, and BMS-754807. We review the important preliminary results from clinical trials with these compounds and conclude with a discussion about future therapeutic efforts. PMID:21875414

  10. Umbilical Cord Derived Mesenchymal Stem Cells Useful in Insulin Production - Another Opportunity in Cell Therapy

    PubMed Central

    Sarang, Shabari; Viswanathan, Chandra

    2016-01-01

    Background and Objectives Type 1 Diabetes Mellitus (T1DM) is an autoimmune disorder resulting out of T cell mediated destruction of pancreatic beta cells. Immunomodulatory properties of mesenchymal stem cells may help to regenerate beta cells and/or prevent further destruction of remnant, unaffected beta cells in diabetes. We have assessed the ability of umbilical cord derived MSCs (UCMSCs) to differentiate into functional islet cells in vitro. Methods and Results We have isolated UCMSCs and allowed sequential exposure of various inducing agents and growth factors. We characterized these cells for confirmation of the presence of islet cell markers and their functionality. The spindle shaped undifferentiated UCMSCs, change their morphology to become triangular in shape. These cells then come together to form the islet like structures which then grow in size and mature over time. These cells express pancreatic and duodenal homeobox −1 (PDX-1), neurogenin 3 (Ngn-3), glucose transporter 2 (Glut 2) and other pancreatic cell markers like glucagon, somatostatin and pancreatic polypeptide and lose expression of MSC markers like CD73 and CD105. They were functionally active as demonstrated by release of physiological insulin and C-peptide in response to elevated glucose concentrations. Conclusions Pancreatic islet like cells with desired functionality can thus be obtained in reasonable numbers from undifferentiated UCMSCs invitro. This could help in establishing a “very definitive source” of islet like cells for cell therapy. UCMSCs could thus be a game changer in treatment of diabetes. PMID:27426087

  11. The Insulin/IGF System in Colorectal Cancer Development and Resistance to Therapy

    PubMed Central

    Vigneri, Paolo Giovanni; Tirrò, Elena; Pennisi, Maria Stella; Massimino, Michele; Stella, Stefania; Romano, Chiara; Manzella, Livia

    2015-01-01

    The insulin/insulin-like growth factor (IGF) system is a major determinant in the pathogenesis and progression of colorectal cancer (CRC). Indeed, several components of this signaling network, including insulin, IGF-1, IGF-2, the IGF-binding proteins, the insulin receptor (IR), the IGF-1 receptor (IGF-1R), and IR substrate proteins 1 and 2 contribute to the transformation of normal colon epithelial cells. Moreover, the insulin/IGF system is also implicated in the development of resistance to both chemotherapeutic drugs and epidermal growth factor receptor targeted agents. The identification of hybrid receptors comprising both the IR and IGF-1R adds further complexity to this signaling network. Thus, a comprehensive understanding of the biological functions performed by each component of the insulin/IGF system is required to design successful drugs for the treatment of CRC patients. PMID:26528439

  12. Consensus evidence-based guidelines for use of insulin pump therapy in the management of diabetes as per Indian clinical practice.

    PubMed

    Kesavadev, Jothydev; Jain, Sunil M; Muruganathan, A; Das, Ashok Kumar

    2014-07-01

    The use of insulin pump in diabetes is likely to increase with recent advances in technology. Although the evidence for the superiority of pumps over multiple daily injections (MDI) is inconsistent, data from accumulating uncontrolled studies indicate greater reductions in glycated haemoglobin in patients switching to continuous subcutaneous insulin infusion (CSII) from MDI therapy. Due to the variability in insulin requirements and sensitivity to CSII pumps, hyperglycaemia in these patients is managed by endocrinologists using individualised therapy. A panel of experts reviewed the existing guidelines and framed recommendations specific to the clinical practice in Indian conditions for use of CSII pumps in the management of hyperglycaemia. Selection of right patient with basic education, motivation and learning skills are essential for successful implementation of CSII therapy with sophisticated programmes. Rapid acting insulin analogues with better pharmacokinetic and pharmacodynamic profile, physical and chemical stability and compatibility with most commercially available insulin pumps are preferred over regular insulin to achieve safe and stable glycaemic control. Further, educating pump users on proper use of CSII pumps, insulin dose adjustments, and handling of accessories are recommended in the current consensus guidelines. Practice of self-monitoring of blood glucose and glycated haemoglobin levels are essential to adjust insulin dosage for the management of diabetes. Use of CSII pumps in special patient populations should be carefully assessed and initiated by endocrinologist. The proposed guidelines can form a basis for use of CSII pumps in the management of hyperglycaemia in the Indian scenario. PMID:25668935

  13. Prolonged low intensity EPOCH–rituximab has improved toxicity in Burkitt lymphoma compared with standard short, high intensity therapy

    PubMed Central

    Shahbazi, Shandiz; Peer, Cody J; Figg, William D

    2014-01-01

    Burkitt lymphoma is an aggressive form of non-Hodgkin lymphoma that has a short doubling time, thus intense short-cycle chemotherapy has been thought to be essential. A recent NCI-sponsored clinical trial investigated DA-EPOCH-R given to 19 HIV-negative patients and a short course regimen (SC-EPOCH-RR) given to 11 HIV-positive patients in hopes of maintaining the efficacy of the regimen while decreasing the typical side effects from the intensive short-cycle chemotherapy. Low intensity EPOCH-R based therapy achieved excellent rates of efficacy despite a significant difference in the median cumulative dose between the DA-EPOCH-R and SC-EPOCH-RR cohorts. Furthermore, both cohorts experienced mainly grade 1 and grade 2 toxicities, with SC-EPOCH-RR cohort patients experiencing less adverse events than DA-EPOCH-R cohort patients. This recent clinical investigation suggests the most important therapeutic principle is not the intensity but rather the length of exposure time above an effective threshold concentration. Since short, intense bolus doses are the standard therapy for Burkitt lymphoma, these findings are clinically relevant and significant. PMID:24919059

  14. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  15. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  16. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  17. 1,5-Anhydro-D-Glucitol Could Reflect Hypoglycemia Risk in Patients with Type 2 Diabetes Receiving Insulin Therapy

    PubMed Central

    Kim, Min Kyeong; Kwak, Soo Heon; Cho, Young Min; Park, Kyong Soo; Kim, Seong Yeon

    2016-01-01

    Background The identification of a marker for hypoglycemia could help patients achieve strict glucose control with a lower risk of hypoglycemia. 1,5-Anhydro-D-glucitol (1,5-AG) reflects postprandial hyperglycemia in patients with well-controlled diabetes, which contributes to glycemic variability. Because glycemic variability is related to hypoglycemia, we aimed to evaluate the value of 1,5-AG as a marker of hypoglycemia. Methods We enrolled 18 adults with type 2 diabetes mellitus (T2DM) receiving insulin therapy and assessed the occurrence of hypoglycemia within a 3-month period. We measured 1,5-AG level, performed a survey to score the severity of hypoglycemia, and applied a continuous glucose monitoring system (CGMS). Results 1,5-AG was significantly lower in the high hypoglycemia-score group compared to the low-score group. Additionally, the duration of insulin treatment was significantly longer in the high-score group. Subsequent analyses were adjusted by the duration of insulin treatment and mean blood glucose, which was closely associated with both 1,5-AG level and hypoglycemia risk. In adjusted correlation analyses, 1,5-AG was negatively correlated with hypoglycemia score, area under the curve at 80 mg/dL, and low blood glucose index during CGMS (P=0.068, P=0.033, and P=0.060, respectively). Conclusion 1,5-AG level was negatively associated with hypoglycemia score determined by recall and with documented hypoglycemia after adjusting for mean glucose and duration of insulin treatment. As a result, this level could be a marker of the risk of hypoglycemia in patients with well-controlled T2DM receiving insulin therapy. PMID:27246285

  18. Application of Histogram Analysis in Radiation Therapy (HART) in Intensity Modulation Radiation Therapy (IMRT) Treatments

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-03-01

    A carcinoma is a malignant cancer that emerges from epithelial cells in structures through out the body.It invades the critical organs, could metastasize or spread to lymph nodes.IMRT is an advanced mode of radiation therapy treatment for cancer. It delivers more conformal doses to malignant tumors sparing the critical organs by modulating the intensity of radiation beam.An automated software, HART (S. Jang et al.,2008,Med Phys 35,p.2812) was used for efficient analysis of dose volume histograms (DVH) for multiple targets and critical organs in four IMRT treatment plans for each patient. IMRT data for ten head and neck cancer patients were exported as AAPM/RTOG format files from a commercial treatment planning system at Northwestern Memorial Hospital (NMH).HART extracted DVH statistics were used to evaluate plan indices and to analyze dose tolerance of critical structures at prescription dose (PD) for each patient. Mean plan indices (n=10) were found to be in good agreement with published results for Linac based plans. The least irradiated volume at tolerance dose (TD50) was observed for brainstem and the highest volume for larynx in SIB treatment techniques. Thus HART, an open source platform, has extensive clinical implications in IMRT treatments.

  19. High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

    PubMed

    Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

    2015-08-15

    The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. PMID:26112241

  20. Insulin resistance: site of the primary defect or how the current and the emerging therapies work.

    PubMed

    Kolaczynski, J W; Caro, J F

    1998-01-01

    Insulin resistance is one of the cardinal pathophysiological components of the metabolic syndrome, type 2 diabetes, and frequently co-exists with essential hypertension. Although insulin resistance is defined as inadequate target organ (muscle, liver and fat) responsiveness and/or sensitivity to insulin, the primary defect may be located in the target organs themselves or at their remote controller--the central nervous system. One of the ways of resolving this dilemma is studying the mechanisms of action of drugs that have insulin-sensitizing properties. In this brief review we discuss how the known and potential insulin sensitizers: metformin, appetite suppressants, thiazolidinediones, and the new class of centrally acting antihypertensive drugs, I1-receptor agonists, may work. PMID:10212839

  1. Effects of Intensive Therapy and Antecedent Hypoglycemia on Counterregulatory Responses to Hypoglycemia in Type 2 Diabetes

    PubMed Central

    Davis, Stephen N.; Mann, Stephanie; Briscoe, Vanessa J.; Ertl, Andrew C.; Tate, Donna B.

    2009-01-01

    OBJECTIVE—The physiology of counterregulatory responses during hypoglycemia in intensively treated type 2 diabetic subjects is largely unknown. Therefore, the specific aims of the study tested the hypothesis that 1) 6 months of intensive therapy to lower A1C <7.0% would blunt autonomic nervous system (ANS) responses to hypoglycemia, and 2) antecedent hypoglycemia will result in counterregulatory failure during subsequent hypoglycemia in patients with suboptimal and good glycemic control. RESEARCH DESIGN AND METHODS—Fifteen type 2 diabetic patients (8 men/7 women) underwent 6-month combination therapy of metformin, glipizide XL, and acarbose to lower A1C to 6.7% and 2-day repeated hypoglycemic clamp studies before and after intensive therapy. A control group of eight nondiabetic subjects participated in a single 2-day repeated hypoglycemic clamp study. RESULTS—Six-month therapy reduced A1C from 10.2 ± 0.5 to 6.7 ± 0.3%. Rates of hypoglycemia increased to 3.2 episodes per patient/month by study end. Hypoglycemia (3.3 ± 0.1 mmol/l) and insulinemia (1,722 ± 198 pmol/l) were similar during all clamp studies. Intensive therapy reduced (P < 0.05) ANS and metabolic counterregulatory responses during hypoglycemia. Antecedent hypoglycemia produced widespread blunting (P < 0.05) of neuroendocrine, ANS, and metabolic counterregulatory responses during subsequent hypoglycemia before and after intensive therapy in type 2 diabetic patients and in nondiabetic control subjects. CONCLUSIONS—Intensive oral combination therapy and antecedent hypoglycemia both blunt physiological defenses against subsequent hypoglycemia in type 2 diabetes. Prior hypoglycemia of only 3.3 ± 0.1 mmol/l can result in counterregulatory failure in type 2 diabetic patients with suboptimal control and can further impair physiological defenses against hypoglycemia in intensively treated type 2 diabetes. PMID:19073776

  2. Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

    SciTech Connect

    Ali, Arif N.; Dhabaan, Anees H.; Jarrio, Christie S.; Siddiqi, Arsalan K.; Landry, Jerome C.

    2012-10-01

    Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V{sub 25} (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V{sub 15} (53.4 Gy vs. 45.9 Gy, p = 0.035), V{sub 20} (32.2 Gy vs. 25.5 Gy, p = 0.016), and V{sub 25} (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

  3. Electroconvulsive therapy in a psychiatric intensive care unit.

    PubMed

    Hafner, R J; Holme, G

    1994-06-01

    This study reviewed all patients (N = 37) treated with ECT in a psychiatric intensive care unit during 1989-91. Diagnoses were: psychotic depression (8); bipolar disorder, manic phase (13); schizoaffective disorder (14); and schizophrenia (2). All patients were very severely disturbed and had failed to respond to medication given at highest levels judged to be safe, usually over 3-4 weeks. Response to ECT was generally rapid and marked, allowing substantial reductions in medication. To achieve the same clinical outcome for each course of ECT, 50% more unilateral than bilateral treatments were required, suggesting that bilateral ECT has a more rapid effect in this highly disturbed population. PMID:7993281

  4. Analysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia

    PubMed Central

    GAO, JIALIN; XIONG, QIANYIN; MIAO, JUN; ZHANG, YAO; XIA, LIBING; LU, MEIQIN; ZHANG, BINHUA; CHEN, YUEPING; ZHANG, ANSU; YU, CUI; WANG, LI-ZHUO

    2015-01-01

    The aims of the present study were to explore the efficacy of glycemic control and the risks of hypoglycemia with different methods of insulin therapy, and to provide reference data for the clinical treatment of diabetes. In this retrospective study, hospitalized patients diagnosed with type 2 diabetes between March and December 2014, in the Department of Endocrinology in the First Affiliated Hospital of Wannan Medical College, were divided into three groups, including an intensive insulin analogue therapy group, a premixed insulin analogue treatment group and a premixed human insulin therapy group. The efficacy of glycemic control and the incidence of hypoglycemia were determined in each of the insulin treatment groups. Compared with the other treatment groups, the intensive insulin analogue therapy group was associated with superior blood glucose control, shorter time to reach standard insulin regimen, shorter hospitalization time, fewer fluctuations in blood glucose levels and lower insulin dosage on discharge from hospital. However, this treatment was also associated with a high risk of hypoglycemia. In conclusion, when combined with the effective prevention of hypoglycemia and appropriate nursing care (especially in hospital care), intensive insulin analogue therapy may provide the greatest benefit to patients. PMID:26137223

  5. [Solcoseryl in intensive therapy in severe craniocerebral trauma].

    PubMed

    Marusanov, V E; Miroshnichenko, A G; Nikolau, S A; Petrova, N V; Bichun, A B

    2000-01-01

    The state of processes of lipid peroxidation and antioxidant defense was studied in patients with severe isolated craniocerebral closed injury. It was found that starting from the first days in the hospital the patients demonstrated marked alterations in the thiol-disulfide and ascorbate metabolism, activation of lipid peroxidation processes and lower antioxidant defense. The use of Solcoseryl as a component of the antioxidant therapy in treatment of the above mentioned category of patients resulted in considerably better indices of the thiol-disulfide metabolism. The isolated use of Solcoseryl failed to influence the ascorbate metabolism and lipid peroxidation. Solcoseryl used in combination with the ascorbic acid led to normalization of the thiol-disulfide and ascorbade metabolism without influencing the lipid peroxidation processes. Combined use of Solcoseryl and ascorbic acid promoted normalization of the neurological status and stabilization of the arterial pressure level. PMID:10983337

  6. Successful management of insulin allergy and autoimmune polyendocrine syndrome type 4 with desensitization therapy and glucocorticoid treatment: a case report and review of the literature.

    PubMed

    Rojas, Joselyn; Villalobos, Marjorie; Martínez, María Sofía; Chávez-Castillo, Mervin; Torres, Wheeler; Mejías, José Carlos; Miquilena, Edgar; Bermúdez, Valmore

    2014-01-01

    Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM). Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS), further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases. PMID:25548690

  7. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    PubMed Central

    Villalobos, Marjorie; Martínez, María Sofía; Chávez-Castillo, Mervin; Mejías, José Carlos; Miquilena, Edgar; Bermúdez, Valmore

    2014-01-01

    Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM). Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS), further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases. PMID:25548690

  8. THE EPENDYMAL ROUTE FOR INSULIN-LIKE GROWTH FACTOR-1 GENE THERAPY IN THE BRAIN

    PubMed Central

    Hereñú, Claudia B.; Sonntag, William E.; Morel, Gustavo R.; Portiansky, Enrique L.; Goya, Rodolfo G.

    2009-01-01

    Intracerebroventricular administration of the peptide insulin-like growth factor-1 (IGF-1) has been shown to be an effective neuroprotective strategy in the brain of different animal models, a major advantage being the achievement of high concentrations of IGF-1 in the brain without altering serum levels of the peptide. In order to exploit this therapeutic approach further, we used high performance recombinant adenoviral (RAd) vectors expressing their transgene under the control of the potent mouse cytomegalovirus immediate early (mCMV) promoter, to transduce brain ependymal cells with high efficiency and to achieve effective release of transgenic IGF-1 into the cerebrospinal fluid (CSF). We constructed RAd vectors expressing either the chimeric protein (TK/GFP)fus (green fluorescent protein fused to HSV1 thymidine kinase) or the cDNA encoding rat IGF-1, both driven by the mCMV promoter. The vectors were injected into the lateral ventricles of young rats and chimeric GFP expression in brain sections was assessed by fluorescence microscopy. The ependymal cell marker vimentin was detected by immunofluorescence and nuclei were labeled with the DNA dye DAPI. Blood and CSF samples were drawn at different times post vector injection. In all cerebral ventricles, vimentin immunoreactive cells of the ependyma were predominantly transduced by RAd-(TK/GFP)fus, showing nuclear and cytoplasmic expression of the transgene. For tanycytes (TK/GFP)fus expression was evident in their cytoplasmic processes as they penetrated deep into the hypothalamic parenchyma. Intracerebroventricular injection of RAd-IGF-1 induced high levels of IGF-1 in the CSF but not in serum. We conclude that the ependymal route constitutes an effective approach for implementing experimental IGF-1 gene therapy in the brain. PMID:19531373

  9. Multiple Daily Injections OR Insulin Pump Therapy: Choosing the Best Option for Your Patient-An Evidence-based Approach.

    PubMed

    Joshi, Mamta; Choudhary, Pratik

    2015-10-01

    Achieving optimal glucose control with minimal hypoglycemia and minimizing the impact of diabetes on quality of life are the aims of management of type 1 diabetes. The main therapeutic options for patients include multiple daily injections (MDI) and continuous subcutaneous insulin therapy (CSII). It is important to differentiate fixed dose MDI with more flexible use, based on carbohydrate counting and structured education programmes, often termed functional insulin therapy (FIT), shown to deliver better outcomes. A significant proportion of patients can achieve optimal glucose control with either therapy, and for those who are unable to achieve desired glucose control with MDI, there is a large body of observational data showing CSII enables them to reduce HbA1c and hypoglycemia, with associated improvements in diabetes-related quality of life. However, in many healthcare systems, guidelines restrict the use of CSII on the basis of cost, with only 20-35 % of patients with type 1 diabetes across Europe using CSII. Although data support improved glucose control and quality of life with CSII, we must recognize that insulin pump therapy is not for everyone and has some downsides such as being attached to a device or issues with cannulas. When we sit down with our patients, we have a responsibility to support those patients with the therapeutic strategy that is best suited to them. In this paper, we review some of the literature that informs this decision-making, highlighting areas where CSII offers clear benefits and also some areas where it may not be appropriate. PMID:26338287

  10. Initiating or Switching to Biphasic Insulin Aspart 30/70 Therapy in Subjects with Type 2 Diabetes Mellitus. An Observational Study

    PubMed Central

    Breum, Leif; Almdal, Thomas; Eiken, Pia; Lund, Per; Christiansen, Erik; on behalf of the Danish BIAsp Study Group

    2008-01-01

    OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in patients with type 2 diabetes (T2D) who initiated insulin with, or switched to, biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METHODS: This was a non-randomized, non-interventional, open-label, observational study involving patients under the care of approximately 150 insulin-prescribing physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine care. Starting dose, dose titration and injection frequency were determined individually by each physician. Information on serious adverse drug reactions (SADR), glycemic parameters and hypoglycemic events were obtained from patients’ notes, patients’ diaries and recall, and transferred to case report forms by physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12 and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided safety data. The age (mean ± SD) was 62.0 ± 11.4 years, body mass index (BMI) 30.4 ± 6.4 kg/m2, duration of diabetes 9.1 ± 8.1 years and HbA1c (%) 9.4 ± 1.7. 199 subjects were prior insulin users and 193 were insulin-naïve patients. Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users -1.2%, insulin-naïve patients -2.2% (both p < 0.001). 28% and 41% of patients, respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower for insulin-naïve patients than for prior insulin users: 5.0 vs. 6.6 episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or switching insulin to, BIAsp 30 in routine care was safe and effective in patients with T2D. PMID:19099087