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  • 1.
    Adolfsson, Peter
    et al.
    Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden; Endocrine and Diabetes Center, The hospital of Halland Kungsbacka, Kungsbacka, Sweden.
    Mattsson, Stig
    Faculty of Health Sciences and Medicine, Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Falun Hospital, Falun, Sweden.
    Jendle, Johan
    Faculty of Health Sciences and Medicine, Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Evaluation of glucose control when a new strategy of increased carbohydrate supply is implemented during prolonged physical exercise in type 1 diabetes2015In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, no 12, p. 2599-2607Article in journal (Refereed)
    Abstract [en]

    Purpose: In healthy individuals, high carbohydrate intake is recommended during prolonged exercise for maximum performance. In type 1 diabetes (T1D), this would alter the insulin requirements. The aim of the study was to evaluate the safety of high glucose supplementation during prolonged exercise and the glucose control when a novel strategy of increased carbohydrate supply was implemented during prolonged exercise in T1D.

    Methods: Eight subjects with T1D participated in a sports camp including sessions of prolonged exercise and individualized feedback during three consecutive days. This was later followed by a 90 km cross-country skiing race. Large amounts of carbohydrates, 75 g/h, were supplied during exercise and the insulin requirements were registered. Glucose was measured before, during and after exercise aiming at euglycaemia, 4-8 mmol/L (72-144 mg/dL). During the race, continuous glucose monitoring (CGM) was used as an aspect of safety and to allow direct and individual adjustments.

    Results: Compared to ordinary carbohydrate supply during exercise, the high carbohydrate supplementation resulted in significantly increased insulin doses to maintain euglycaemia. During the cross-country skiing race, the participants succeeded to reach mean target glucose levels; 6.5 ± 1.9 mmol/L (117 ± 34 mg/dL) and 5.7 ± 1.5 mmol/L (103 ± 27 mg/dL) at the start and finish of the race, respectively. Episodes of documented hypoglycemia (<4 mmol/L/72 mg/dL) were rare. CGM was used for adjustments.

    Conclusion: In this study, large carbohydrate supplementation in T1D individuals during prolonged aerobic exercise is safe and allows the subjects to maintain glycaemic control and indicates the feasibility of CGM under these conditions.

  • 2.
    Adolfsson, Peter
    et al.
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; The Queen Silvia Children's Hospital, Göteborg, Sweden.
    Ornhagen, Hans
    Swedish Sports Diving Federation, Idrottshuset, Farsta, Sweden.
    Eriksson, Bengt M.
    Hyperbaric Medicine, Department of Anesthesiology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
    Gautham, Raghavendhar
    Medtronic Diabetes, Northridge CA, USA.
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    In-vitro performance of the Enlite sensor in various glucose concentrations during hypobaric and hyperbaric conditions2012In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 6, no 6, p. 1375-1382Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for reliable methods of glucose measurement in different environmental conditions. The objective of this in vitro study was to evaluate the performance of the Enlite® Sensor when connected to either the iPro™ Continuous Glucose Monitor recording device or the Guardian® REAL-Time transmitting device, in hypobaric and hyperbaric conditions.

    Methods: Sixteen sensors connected to eight iPro devices and eight Guardian REAL-Time devices were immersed in three beakers containing separate glucose concentrations: 52, 88, and 207 mg/dl (2.9, 4.9, and 11.3 mmol/liter). Two different pressure tests were conducted: a hypobaric test, corresponding to maximum 18000 ft/5500 m height, and a hyperbaric test, corresponding to maximum 100 ft/30 m depth. The linearity of the sensor signals in the different conditions was evaluated.

    Results: The sensors worked continuously, and the sensor signals were collected without interruption at all pressures tested. When comparing the input signals for glucose (ISIGs) and the different glucose concentrations during altered pressure, linearity (R(2)) of 0.98 was found. During the hypobaric test, significant differences (p < .005) were seen when comparing the ISIGs during varying pressure at two of the glucose concentrations (52 and 207 mg/dl), whereas no difference was seen at the 88 mg/dl glucose concentration. During the hyperbaric test, no differences were found.

    Conclusions: The Enlite Sensors connected to either the iPro or the Guardian REAL-Time device provided values continuously. In hyperbaric conditions, no significant differences were seen during changes in ambient pressure; however, during hypobaric conditions, the ISIG was significantly different in the low and high glucose concentrations.

  • 3.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy,University of Gothenburg, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Eriksson, Bengt M.
    Hyperbaric Medicine, Department of Anesthesiology, Karolinska University Hospital, Solna, Sweden.
    Cooper, Ken
    Medtronic Diabetes (Sensor R&D), Northridge CA, USA.
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Continuous glucose monitoring: a study of the Enlite sensor during hypo- and hyperbaric conditions2012In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 14, no 6, p. 527-532Article in journal (Refereed)
    Abstract [en]

    Background: The performance and accuracy of the Enlite(™) (Medtronic, Inc., Northridge, CA) sensor may be affected by microbubble formation at the electrode surface during hypo- and hyperbaric conditions. The effects of acute pressure changes and of prewetting of sensors were investigated.

    Materials and Methods: On Day 1, 24 sensors were inserted on the right side of the abdomen and back in one healthy individual; 12 were prewetted with saline solution, and 12 were inserted dry. On Day 2, this procedure was repeated on the left side. All sensors were attached to an iPro continuous glucose monitoring (CGM) recorder. Hypobaric and hyperbaric tests were conducted in a pressure chamber, with each test lasting 105 min. Plasma glucose values were obtained at 5-min intervals with a HemoCue(®) (Ängelholm, Sweden) model 201 glucose analyzer for comparison with sensor glucose values.

    Results: Ninety percent of the CGM systems operated during the tests. The mean absolute relative difference was lower during hyperbaric than hypobaric conditions (6.7% vs. 14.9%, P<0.001). Sensor sensitivity was slightly decreased (P<0.05) during hypobaric but not during hyperbaric conditions. Clarke Error Grid Analysis showed that 100% of the values were found in the A+B region. No differences were found between prewetted and dry sensors.

    Conclusions: The Enlite sensor performed adequately during acute pressure changes and was more accurate during hyperbaric than hypobaric conditions. Prewetting the sensors did not improve accuracy. Further studies on type 1 diabetes subjects are needed under various pressure conditions.

  • 4.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute for the Health of Women and Children, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Faculty of Health Sciences, Örebro University Hospital, Örebro, Sweden.
    Accuracy and reliability of continuous glucose monitoring in individuals with type 1 diabetes during recreational diving2009In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 11, no 8, p. 493-497Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study evaluated the accuracy and function of the Continuous Glucose Monitoring System (CGMS, Minneapolis, MN) during recreational scuba diving in individuals with type 1 diabetes.

    METHODS: Twenty-four adults, 12 with type 1 diabetes and 12 healthy controls, were studied during five recreational scuba dives performed on three consecutive days. All the participants used the CGMS on all the days and during all the dives. Comparisons were made between plasma glucose at specific time intervals and the CGMS.

    RESULTS: The recording by the CGMS was robust, with few sensor problems. The mean sensor survival time was >48 h. Eighty-five percent of the individuals used one sensor during the entire length of the trial. The overall mean absolute difference (MAD) within the group with diabetes was 14.4 +/- 6%, and the corresponding daily figures were 23.2 +/- 19.3% on day 1, 11.6 +/- 4.5% on day 2, and 11.2 +/- 5.7% on day 3. A significant improvement regarding MAD when day 1 was compared with day 2 and 3 (P < 0.05). With a limit set at 70 mg/dL, hypoglycemia pre- and post-dive was detected with a positive predictive value of 0.39, negative predictive value of 0.98, sensitivity of 0.64, and specificity of 0.94.

    CONCLUSIONS: We demonstrate that the CGMS was used with accuracy in such difficult conditions as scuba diving and provided robust information on glucose variations.

  • 5.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Centre, Department of Pediatrics, Institute for the Health of Women and Children, the Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sportsdiving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    The benefits of continuous glucose monitoring and a glucose monitoring schedule in individuals with type 1 diabetes during recreational diving2008In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 2, no 5, p. 778-784Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our objective is to evaluate the Medtronic CGMS continuous glucose monitoring system and plasma glucose (PG) measurement performed in a monitoring schedule as tools to identify individuals with type 1 diabetes at risk when diving.

    METHODS: We studied 24 adults, 12 type 1 diabetes subjects and 12 controls, during 5 recreational scuba dives performed on 3 consecutive days. The CGMS was used by all participants on all the days and all the dives. Comparisons were made between PG performed in a monitoring schedule during the days of diving, self-monitored blood glucose (SMBG) performed 2 weeks prior to diving, and the CGMS during the study.

    RESULTS: One hundred seventeen dives were performed. Hypoglycemia (<70 mg/dl) was found in six individuals and on nine occasions. However, no symptoms of hypoglycemia were present during or immediately postdiving. In one case, repetitive hypoglycemia prediving gave rise to a decision not to dive. None of the dives were aborted. The number of hypoglycemic episodes, 10 min prediving or immediately postdiving, were related to the duration of diabetes, r = 0.83 and p =0.01, and the percentage of SMBG values below target (<72 mg/dl), r = 0.65 and p =0.02. Moreover, the number of hypoglycemic episodes was also related to the total duration below low limit (<70 mg/dl), measured by the CGMS, r =0.74 and p =0.006.

    CONCLUSION: Safe dives are possible to achieve by well-informed, well-controlled individuals with type 1 diabetes. Using downloaded SMBG, CGMS, and repetitive PG in a monitoring schedule, it is possible to identify those subjects who are suitable for diving.

  • 6. Birkeland, Kare I.
    et al.
    Home, Philip D.
    Wendisch, Ulrich
    Ratner, Robert E.
    Johansen, Thue
    Endahl, Lars A.
    Lyby, Karsten
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences.
    Roberts, Anthony P.
    DeVries, J. Hans
    Meneghini, Luigi F.
    Insulin degludec in type 1 diabetes: a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine2011In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 34, no 3, p. 661-665Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.

    RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.

    RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.

    CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.

  • 7.
    Blonde, Lawrence
    et al.
    Department of Endocrinology, Ochsner Medical Center, New Orleans LA, USA.
    Jendle, Johan
    Örebro University, School of Medical Sciences. Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Gross, Jorge
    Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
    Woo, Vincent
    Section of Endocrinology and Metabolism, University of Manitoba, Winnipeg MB, Canada.
    Jiang, Honghua
    Lilly Diabetes, Eli Lilly and Company, Indianapolis IN, USA.
    Fahrbach, Jessie L.
    Diabetes, Eli Lilly and Company, Indianapolis IN, USA.
    Milicevic, Zvonko
    Lilly Research Laboratories, Vienna, Austria.
    Once-weekly dulaglutide versus bedtime insulin glargine, both in combination with prandial insulin lispro, in patients with type 2 diabetes (AWARD-4): a randomised, open-label, phase 3, non-inferiority study2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9982, p. 2057-2066Article in journal (Refereed)
    Abstract [en]

    Background: For patients with type 2 diabetes who do not achieve target glycaemic control with conventional insulin treatment, advancing to a basal-bolus insulin regimen is often recommended. We aimed to compare the efficacy and safety of long-acting glucagon-like peptide-1 receptor agonist dulaglutide with that of insulin glargine, both combined with prandial insulin lispro, in patients with type 2 diabetes.

    Methods: We did this 52 week, randomised, open-label, phase 3, non-inferiority trial at 105 study sites in 15 countries. Patients (aged ≥18 years) with type 2 diabetes inadequately controlled with conventional insulin treatment were randomly assigned (1:1:1), via a computer-generated randomisation sequence with an interactive voice-response system, to receive once-weekly dulaglutide 1·5 mg, dulaglutide 0·75 mg, or daily bedtime glargine. Randomisation was stratified by country and metformin use. Participants and study investigators were not masked to treatment allocation, but were unaware of dulaglutide dose assignment. The primary outcome was a change in glycated haemoglobin A1c (HbA1c) from baseline to week 26, with a 0·4% non-inferiority margin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01191268.

    Findings: Between Dec 9, 2010, and Sept 21, 2012, we randomly assigned 884 patients to receive dulaglutide 1·5 mg (n=295), dulaglutide 0·75 mg (n=293), or glargine (n=296). At 26 weeks, the adjusted mean change in HbA1c was greater in patients receiving dulaglutide 1·5 mg (-1·64% [95% CI -1·78 to -1·50], -17·93 mmol/mol [-19·44 to -16·42]) and dulaglutide 0·75 mg (-1·59% [-1·73 to -1·45], -17·38 mmol/mol [-18·89 to -15·87]) than in those receiving glargine (-1·41% [-1·55 to -1·27], -15·41 mmol/mol [-16·92 to -13·90]). The adjusted mean difference versus glargine was -0·22% (95% CI -0·38 to -0·07, -2·40 mmol/mol [-4·15 to -0·77]; p=0·005) for dulaglutide 1·5 mg and -0·17% (-0·33 to -0·02, -1·86 mmol/mol [-3·61 to -0·22]; p=0·015) for dulaglutide 0·75 mg. Five (<1%) patients died after randomisation because of septicaemia (n=1 in the dulaglutide 1·5 mg group); pneumonia (n=1 in the dulaglutide 0·75 mg group); cardiogenic shock; ventricular fibrillation; and an unknown cause (n=3 in the glargine group). We recorded serious adverse events in 27 (9%) patients in the dulaglutide 1·5 mg group, 44 (15%) patients in the dulaglutide 0·75 mg group, and 54 (18%) patients in the glargine group. The most frequent adverse events, arising more often with dulaglutide than glargine, were nausea, diarrhoea, and vomiting.

    Iinterpretation: Dulaglutide in combination with lispro resulted in a significantly greater improvement in glycaemic control than did glargine and represents a new treatment option for patients unable to achieve glycaemic targets with conventional insulin treatment.

    FUNDING: Eli Lilly and Company.

  • 8.
    Brunner, G. A.
    et al.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Balent, B.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Ellmerer, M.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Schaupp, L.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Siebenhofer, A.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Jendle, Johan
    Novo Nordisk A/S, Copenhagen, Denmark.
    Okikawa, J.
    Aradigm Corp., Hayward, California, USA.
    Pieber, T. R.
    Department of Internal Medicine, Karl-Franzens University, Graz, Austria.
    Dose-response relation of liquid aerosol inhaled insulin in type I diabetic patients.2001In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 44, no 3, p. 305-308Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: The AERx insulin Diabetes Management system (AERx iDMS) is a liquid aerosol device that enables insulin to be administered to the peripheral parts of the lung. This study aimed to compare the pharmacokinetic and pharmacodynamic properties of insulin which is inhaled using AERx iDMS with insulin which is subcutaneously administered.

    METHODS: In total, 18 C-peptide negative patients with Type I (insulin-dependent) diabetes mellitus participated in this randomised, open-label, 5-period crossover trial. Human regular insulin was administered subcutaneously (0.12 U/kg body weight) or inhaled by means of the AERx iDMS (dosages 0.3, 0.6, 1.2, and 1.8 U/kg body weight). Thereafter plasma glucose was kept constant at 7.2 mmol/l for a 10-h period (glucose clamp technique).

    RESULTS: Inhaled insulin provided a dose-response relation that was close to linear for both pharmacokinetic (AUC-Ins(0-10 h); Cmax-Ins) and pharmacodynamic (AUC-GIR(0-10 h); GIRmax) parameters. Time to maximum insulin concentration (Tmax-Ins) and time to maximum glucose infusion rate (TGIRmax) were shorter with inhaled insulin than with subcutaneous administration. The pharmacodynamic system efficiency of inhaled insulin (AUC-GIR(0-6 h) was 12.7% (95% C.I.: 10.2-15.6).

    CONCLUSION/INTERPRETATION: The inhalation of soluble human insulin using the AERx iDMS is feasible and provides a clear dose response. Further long-term studies are required to investigate safety aspects, HbA1c values, incidence of hypoglycaemic events and the quality of life.

  • 9. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycaemia across patient subgroups in routine clinical care: The ReFLeCT study2019Conference paper (Other academic)
  • 10. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycemia (according to different definitions) in routine clinical care: The ReFLeCT Study2019Conference paper (Other academic)
  • 11. de Valk, H.W.
    et al.
    Feher, M.
    Krarup Hansen, T.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Merchante, A.
    Koefoed, M.M.
    Rizi, E.P.
    Zimmermann, E.
    Fadini, G.P.
    Switching to insulin degludec from other basal insulins reduces rates of hypoglycemia across patient subgroups in routine clinical care: The ReFleCT study2019Conference paper (Other academic)
    Abstract [en]

    ReFLeCT, a multicenter, prospective, observational study evaluated the safety and effectiveness of switching from other basal insulins to insulin degludec (degludec) in patients with type 1 (T1D) or type 2 diabetes (T2D) in routine clinical practice. ReFLeCT comprised a 4-week baseline period (pre-switch basal insulin) and 12-month follow-up period (degludec). The primary endpoint of overall hypoglycemia reported in patient diaries was reduced during the 12-month follow-up period vs. baseline, without compromising glycemic control. In pre-specified subgroup analyses of the primary endpoint, we assessed if the overall result was robust in different subgroups, characterized according to baseline A1C (<7.5, ≥7.5-<8.5, ≥8.5-<9.5, ≥9.5%), diabetes duration (quartiles) and physician’s reason for initiating degludec (hypoglycemia [Yes/No]). The estimated rate ratios of hypoglycemia were similar within subgroups (no significant interactions), and demonstrated overall lower rates (the majority significantly lower) during the 12-month follow-up periods vs. baseline in patients with T1D or T2D (Figure). Irrespective of baseline characteristics or physician’s reason for initiating degludec, switching to degludec from other basal insulins reduced rates of overall hypoglycemia in patients with T1D or T2D, in routine clinical practice.

  • 12.
    Evans, M.
    et al.
    University Hospital Llandough, Cardiff, UK.
    Ridderstråle, M.
    Steno Diabetes Center, Gentofte, Denmark.
    Jensen, H. H.
    Incentive, Holte, Denmark.
    Bøgelund, M.
    Novo Nordisk Ltd., Gatwick, United Arab Emirates.
    Jensen, M. M.
    Novo Nordisk, Copenhagen, Denmark.
    Ericsson, Å.
    Novo Nordisk Scandinavia AB, Malmö, Sweden.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Quantifying The Short-Term Impact of Changes In Hba1c, Weight And Insulin Regimen on Health Related Quality-of-Life2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 7, p. A616-A616Article in journal (Refereed)
  • 13.
    Fadini, G. P.
    et al.
    Department of Medicine, Division of Metabolic Diseases, University of Padova, Padova, Italy.
    Feher, M.
    Beta Cell Diabetes Centre, Chelsea and Westminster Hospital, London, UK; University of Surrey, Guildford, UK.
    Hansen, T. K.
    Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
    de Valk, H. W.
    Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
    Koefoed, M. M.
    Novo Nordisk A/S, Søborg, Denmark.
    Wolden, M.
    Novo Nordisk A/S, Søborg, Denmark.
    Zimmermann, E.
    Novo Nordisk A/S, Søborg, Denmark.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Reduced rates of overall hypoglycaemia in patients with Type 1 diabetes after switching to insulin degludec: A European, multinational, multicentre, prospective, observational study (ReFLeCT)2019In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 36, no Suppl. 1, p. 60-60Article in journal (Other academic)
    Abstract [en]

    Aims: To evaluate the safety and effectiveness of switching to once‐daily insulin degludec (degludec) from other basal insulins in patients with Type 1 diabetes in routine clinical practice.

    Methods: ReFLeCT was a multicentre, prospective, observational study in seven European countries in patients (≥18 years) with Type 1 or Type 2 diabetes, whose physician planned to switch their basal insulin to degludec (ClinicalTrials.gov: NCT02392117). ReFLeCT comprised a four week baseline period (pre‐switch basal insulin) and a 12 month follow‐up period (degludec). For the Type 1 diabetes cohort presented here, primary endpoint was changed from baseline in the rate of overall hypoglycaemia recorded in patient diaries.

    Results: Baseline characteristics (mean [SD]) for patients with Type 1 diabetes (n = 556) were: age 47.4 (15.7) years, diabetes duration 21.4 (13.5) years, HbA1c 8.1 (1.3)% (65.0 [14.2]mmol/mol), fasting plasma glucose (FPG) 8.8 (3.9)mmol/l, pre‐switch basal insulin dose 25.0 (14.1)u/day, body mass index (BMI) 26.1 (4.7)kg/m2 and body weight 76.4 (15.6)kg. Estimated rate ratios of overall (0.80 [0.74; 0.88]95%CI), non‐severe (0.81 [0.74; 0.88]95%CI), severe (American Diabetes Association definition; 0.28 [0.14; 0.56]95%CI) and nocturnal (00:01−05:59am; 0.61 [0.50; 0.73]95%CI) hypoglycaemia illustrated significantly lower rates during 12 month follow‐up vs baseline. HbA1c, FPG and basal insulin dose decreased significantly by –0.15% [–0.23; –0.07]95%CI (–1.64mmol/mol [–2.51; –0.77]95%CI), –0.54mmol/l [–0.95; –0.14]95%CI and –2.21u/day [–2.90; –1.53]95%CI, respectively, and body weight was 0.79kg [0.38; 1.20]95%CI higher, at 12 month follow‐up vs baseline.

    Conclusion: Switching from other basal insulins to degludec significantly reduced the rates of hypoglycaemia and improved glycaemic control at lower basal insulin doses in patients with Type 1 diabetes in routine clinical practice.

  • 14.
    Fadini, G. P.
    et al.
    Department of Medicine, Division of Metabolic Diseases, University of Padova, Padova, Italy.
    Feher, M.
    Beta Cell Diabetes Centre, Chelsea and Westminster Hospital, London, UK; University of Surrey, Guildford, UK.
    Hansen, T. K.
    Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
    de Valk, H. W.
    Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
    Koefoed, M. M.
    Novo Nordisk A/S, Søborg, Denmark.
    Wolden, M.
    Novo Nordisk A/S, Søborg, Denmark.
    Zimmermann, E.
    Novo Nordisk A/S, Søborg, Denmark.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Reduced rates of overall hypoglycaemia in patients with Type 2 diabetes after switching to insulin degludec: A European, multinational, multicentre, prospective, observational study (ReFLeCT)2019In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 36, no Suppl. 1, p. 60-60Article in journal (Other academic)
    Abstract [en]

    Aims: To evaluate the safety and effectiveness of switching to once‐daily insulin degludec (degludec) from other basal insulins in patients with Type 2 diabetes in routine clinical practice.

    Methods: ReFLeCT was a multicentre, prospective, observational study in seven European countries in patients (≥18 years) with Type 1 or Type 2 diabetes, whose physician planned to switch their basal insulin to degludec (ClinicalTrials.gov:NCT02392117). ReFLeCT comprised a four week baseline period (pre‐switch basal insulin) and a 12 month follow‐up period (degludec). For the Type 2 diabetes cohort presented here, primary endpoint was changed from baseline in the rate of overall hypoglycaemia recorded in patient diaries.

    Results: Baseline characteristics (mean [SD]) for patients with Type 2 diabetes (n = 611) were: age 65.2 (9.6) years, diabetes duration 18.0 (9.5) years, HbA1c 8.2 (1.4)% (66.1 [15.3]mmol/mol), fasting plasma glucose (FPG) 9.0 (3.1)mmol/l, pre‐switch basal insulin dose 37.5 (33.9)u/day, body mass index (BMI) 31.1 (6.3)kg/m2, body weight 87.6 (19.6)kg and 421 (68.9%) patients used a basal‐bolus regimen. Estimated rate ratios of overall (0.46 [0.38; 0.56]95%CI), non‐severe (0.46 [0.38; 0.56]95%CI) and nocturnal (00:01−05:59am; 0.35 [0.20; 0.62]95%CI) hypoglycaemia illustrated significantly lower rates during 12 month follow‐up vs baseline (severe hypoglycaemia [American Diabetes Association definition], too few events for statistical analysis). HbA1c and FPG decreased significantly by −0.32% [−0.42; −0.22]95%CI (−3.50 mmol/mol [−4.59; −2.40]95%CI) and −0.84mmol/l [−1.09; −0.60]95%CI, respectively, with no significant changes in basal insulin dose or body weight at 12 month follow‐up vs baseline.

    Conclusion: Switching from other basal insulins to degludec reduced the rates of hypoglycaemia and improved glycaemic control in patients with Type 2 diabetes in routine clinical practice.

  • 15.
    Fadini, Gian Paolo
    et al.
    Department of Medicine, Division of Metabolic Diseases, University of Padova, Padova, Italy.
    Feher, Michael
    Beta Cell Diabetes Centre, Chelsea and Westminster Hospital, London, UK; Department of Clinical and Experimental Medicine, University of Surrey, Guilford, UK.
    Hansen, Troels Krarup
    Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
    de Valk, Harold W.
    Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
    Koefoed, Mette Marie
    Novo Nordisk A/S, Søborg, Denmark.
    Wolden, Michael
    Novo Nordisk A/S, Søborg, Denmark.
    Zimmerman, E.
    Novo Nordisk A/S, Søborg, Denmark.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Switching to Degludec from Other Basal Insulins is Associated with Reduced Hypoglycemia Rates: a Prospective Study2019In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, article id jc.2019-01021Article in journal (Refereed)
    Abstract [en]

    CONTEXT: Observational studies of insulin degludec (degludec) with hypoglycemia events prospectively recorded are lacking.

    OBJECTIVE: To evaluate the safety and effectiveness of degludec in patients with type 1 (T1D) or type 2 diabetes (T2D) switching from other basal insulins in routine care.

    DESIGN: ReFLeCT was a multinational, multicenter, prospective, observational, single-arm study comprising a 4-week baseline period (pre-switch basal insulin) and 12-month follow-up (degludec).

    SETTING: Routine clinical practice. Patients or Other Participants: Insulin-treated patients (≥18 years) with T1D (n=556) or T2D (n=611) with treatment plans to initiate degludec.

    INTERVENTIONS: Switching to degludec from other basal insulins.

    MAIN OUTCOME MEASURE(S): Change from baseline in number of overall hypoglycemic events recorded in patient diaries.

    RESULTS: In T1D, the 12-month follow-up/baseline rate ratios [95% CI] of overall (0.80 [0.74;0.88]), non-severe (0.83 [0.76;0.91]), severe (0.28 [0.14;0.56]) and nocturnal (0.61 [0.50;0.73]) hypoglycemia suggested significantly reduced hypoglycemia rates with degludec (all P<0.001). At 12 months, HbA1c, fasting plasma glucose (FPG) and basal insulin dose decreased significantly. Body weight increased and treatment satisfaction improved significantly. In T2D, the hypoglycemia rate ratios were: overall (0.46 [0.38;0.56]), non-severe (0.53 [0.44;0.64]) and nocturnal (0.35 [0.20;0.62]) (all P<0.001; too few events for analysis of severe). At 12 months, HbA1c and FPG decreased significantly. Body weight and insulin doses remained unchanged, and treatment satisfaction was significantly improved.

    CONCLUSIONS: In a routine clinical care setting, switching to degludec from other basal insulins was associated with significantly reduced rates of hypoglycemia, improved glycemic control, and treatment satisfaction in patients with T1D or T2D.

  • 16.
    Faerch, Mia
    et al.
    Department of Human Genetics, Aarhus University, Denmark; Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark.
    Corydon, Thomas J.
    Department of Human Genetics, Aarhus University, Denmark.
    Rittig, Søren
    Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark.
    Christensen, Jane H.
    Department of Human Genetics, Aarhus University, Denmark; Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark.
    Hertz, Jens Michael
    Department of Clinical Genetics, Aarhus University Hospital, Denmark.
    Jendle, Johan
    Faculty of Health Sciences, Örebro University Hospital, Sweden.
    Skewed X-chromosome inactivation causing diagnostic misinterpretation in congenital nephrogenic diabetes insipidus2010In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 44, no 5, p. 324-330Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To establish the clinical phenotype and genetic background in a family with diabetes insipidus.

    MATERIAL AND METHODS: The subjects were a sister and brother, aged 34 and 27 years, respectively, with a history of polyuria since infancy. Clinical testing confirmed a diagnosis of congenital nephrogenic diabetes insipidus (CNDI) in both. Samples of purified genomic DNA were analysed.

    RESULTS: The sequence of the entire coding region of the AQP2 gene as well as the AVPR2 gene was determined. Sequence analysis revealed no variations in the AQP2 gene. A missense variation in exon 2 of the AVPR2 gene (g.685G>A), predicting a p.Asp85Asn substitution, was identified in the X-chromosome of the affected male and one allele in the sister and the asymptomatic mother. The p.Asp85Asn variation in AVPR2 is known to cause CNDI, and has previously been described as inducing a partial phenotype treatable with dDAVP. However, in this family dDAVP had no influence on urine osmolality, whereas combination therapy with indomethacin and hydrochlorothiazide increased urine osmolality to 299 mosm/l in the proband. A skewed X-inactivation pattern (93%) occurring in the normal X allele was recognized in the sister.

    CONCLUSIONS: This study demonstrates the effect of skewed X-chromosome inactivation associated with X-linked CNDI. Polydipsia in early childhood could be due to X-linked CNDI despite affecting both genders. The significant heterogeneity in the clinical phenotype in CNDI carries a risk of diagnostic misinterpretation and emphasizes the need for genetic characterization. Treatment combining indomethacin and hydrochlorothiazide results in a marked response on both urine output and urine osmolality.

  • 17.
    Feher, M.
    et al.
    Beta Cell Diabetes Centre, Chelsea and Westminster Hospital, London, UK; University of Surrey, Guildford, UK.
    Fadini, G.P.
    Department of Medicine, Division of Metabolic Diseases, University of Padova, Padova, Italy.
    Krarup Hansen, T.
    Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Merchante, A.
    University General Hospital of Castellón, Castellón de la Plana, Spain; Jaume I University, Castellón de la Plana, Spain.
    Koefoed, M.M.
    Novo Nordisk A/S, Søborg, Denmark.
    Rizi, E.P.
    Novo Nordisk A/S, Søborg, Denmark.
    Zimmermann, E.
    Novo Nordisk A/S, Søborg, Denmark.
    de Valk, H.W.
    Department of Internal Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
    Hypoglycaemia, irrespective of the definition used, is reduced when switching to insulin degludec from other basal insulins in routine clinical care: The ReFLeCT study2019Conference paper (Other academic)
    Abstract [en]

    Background and aims: ReFLeCT was a multicentre, prospective, observational study designed to investigate the safety and effectiveness of switching to insulin degludec (degludec) from other basal insulins in patients with type 1 (T1D) or type 2 diabetes (T2D). Few studies had prospectively collected hypoglycaemia data from patient diaries following a switch to degludec in everyday clinical practice. These additional analyses from the ReFLeCT study aimed to assess the effects of switching to degludec according to different hypoglycaemia definitions.

    Materials and methods: ReFLeCT comprised a 4-week baseline period (pre-switch basal insulin) and a 12-month follow-up period (degludec treatment). The primary endpoint of overall hypoglycaemia reported in patient diaries was reduced during follow-up vs baseline in T1D and T2D with improvement of glycaemic control, as previously reported. Here, hypoglycaemia data from ReFLeCT were analysed using pre-specified and updated (post hoc) American Diabetes Association (ADA) hypoglycaemia definitions. Definitions consisted of: documented asymptomatic and symptomatic, pseudo, probable symptomatic, and Level 1, 2 and 3 (severe) hypoglycaemia (Fig). Hypoglycaemic events were analysed using fully adjusted, negative binomial regression models.

    Results: In T1D (n=556) and T2D (n=611), estimated rate ratios across the previous and the updated ADA hypoglycaemia definitions were significantly lower during the 12-month follow-up vs the baseline period, except for asymptomatic hypoglycaemia in T1D and Level 3 hypoglycaemia in T2D (due to a low number of severe hypoglycaemic events, no comparable statistics were performed) (Fig). Event rates per patient year were also lower for all definitions during the 12-month follow-up vs the baseline period, except for Level 3 hypoglycaemia in T2D, which marginally increased, although this was likely due to the low number of events in this group.

    Conclusion: In patients with T1D and T2D, switching to degludec from other basal insulins in routine clinical care is associated with lower rates of hypoglycaemia across a broad range of hypoglycaemia definitions, in combination with improved glycaemic control.

  • 18. Freemantle, N
    et al.
    Meneghini, L
    Christensen, T
    Wolden, M L
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ratner, R
    Insulin degludec improves health-related quality of life (SF-36(®) ) compared with insulin glargine in people with Type 2 diabetes starting on basal insulin: a meta-analysis of phase 3a trials2013In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 30, no 2, p. 226-232Article in journal (Refereed)
    Abstract [en]

    AIM: To compare the effect of insulin degludec and insulin glargine on health-related quality of life in patients with Type 2 diabetes starting on insulin therapy.

    METHODS: Patient-level data from three open-label, randomized, treat-to-target trials of 26 or 52 weeks' duration were pooled using a weighted analysis in conjunction with a fixed-effects model. Insulin-naive patients received either insulin degludec (n = 1290) or insulin glargine (n = 632) once daily, in combination with oral anti-diabetic drugs. Glycaemic control was assessed via HbA(1c) and fasting plasma glucose concentrations. Rates of hypoglycaemia, defined as plasma glucose < 3.1 mmol/l (< 56 mg/dl), were recorded. Health-related quality of life was evaluated using the 36-item Short Form (SF-36(®) ) version 2 questionnaire. Statistical analysis was performed using a generalized linear model with treatment, trial, anti-diabetic therapy at baseline, gender, region and age as explanatory variables.

    RESULTS: Insulin degludec was confirmed as non-inferior to insulin glargine based on HbA(1c) concentrations. In each trial comprising the meta-analysis, fasting plasma glucose and confirmed overall and nocturnal (00.01-05.59 h) hypoglycaemia were all numerically or significantly lower with insulin degludec vs. insulin glargine. At endpoint, the overall physical health component score was significantly higher (better) with insulin degludec vs. insulin glargine [+0.66 (95% CI 0.04-1.28)], largely attributable to a difference [+1.10 (95% CI 0.22-1.98)] in the bodily pain domain score. In the mental domains, vitality was significantly higher with insulin degludec vs. insulin glargine [+0.81 (95% CI 0.01-1.59)].

    CONCLUSIONS: Compared with insulin glargine, insulin degludec leads to improvements in both mental and physical health status for patients with Type 2 diabetes initiating insulin therapy.

  • 19.
    Galavazi, Marije
    et al.
    Örebro University, School of Medical Sciences.
    Jansson, Stefan P. O.
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Karlsson, Jan
    Örebro University, School of Medical Sciences. Örebro University Hospital.
    Long-term effects of low energy diet combined with CBT-based group treatment of patients with obesity on weight, quality of life and eating behaviour: a 2-year intervention study2018Conference paper (Other academic)
  • 20.
    Goodall, G.
    et al.
    IMS Health, Basel, Switzerland.
    Jendle, Johan
    Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    Valentine, W. J.
    IMS Health, Basel, Switzerland.
    Munro, V.
    Novo Nordisk Ltd, Crawley, West Sussex, UK.
    Brandt, A. B.
    Novo Nordisk Scandinavia AB, Malmö, Sweden.
    Ray, J. A.
    IMS Health, Basel, Switzerland.
    Roze, S.
    IMS Health, Basel, Switzerland.
    Foos, V.
    IMS Health, Basel, Switzerland.
    Palmer, A. J.
    IMS Health, Basel, Switzerland.
    Biphasic insulin aspart 70/30 vs. insulin glargine in insulin naïve type 2 diabetes patients: modelling the long-term health economic implications in a Swedish setting2008In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 62, no 6, p. 869-876Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate the long-term clinical and economic outcomes of biphasic insulin aspart 70/30 (BIAsp 70/30) treatment vs. insulin glargine in insulin naïve, type 2 diabetes patients failing oral antidiabetic drugs in a Swedish setting.

    METHODS: A published and validated computer simulation model (the CORE Diabetes Model) was used to project life expectancy, quality-adjusted life expectancy (QALE) and costs over patient lifetimes. Cohort characteristics [54.5% male, mean age 52.4 years, 9 years mean diabetes duration, mean glycosylated haemoglobin (HbA1c) 9.77%] and treatment effects were based on results from the Initiate Insulin by Aggressive Titration and Education (INITIATE) clinical trial. Direct medical costs were accounted in 2006 Swedish Kronor (SEK) and economic and clinical benefits were discounted at 3% per annum.

    RESULTS: Biphasic insulin aspart 70/30 treatment when compared with insulin glargine treatment was associated with improvements in discounted life expectancy of 0.21 years (13.10 vs. 12.89 years) and QALE of 0.21 quality-adjusted life years (QALYs) (9.16 vs. 8.96 QALYs). Reductions in the incidence of diabetes-related complications in the BIAsp 70/30 treatment arm led to reduced total costs of SEK 10,367 when compared with insulin glargine (SEK 396,475 vs. SEK 406,842) over patient lifetimes. BIAsp 70/30 treatment was projected to be dominant (cost and lifesaving) when compared with insulin glargine in the base case analysis.

    CONCLUSIONS: Biphasic insulin aspart 70/30 treatment was associated with improved clinical outcomes and reduced costs compared with insulin glargine treatment over patient lifetimes. These results were driven by improved HbA1c levels associated with BIAsp 70/30 compared with insulin glargine and the accompanying reduction in diabetes-related complications despite increases in body mass index.

  • 21.
    Himmelmann, Anders
    et al.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Jendle, Johan
    Novo Nordisk A/S, Copenhagen, Denmark.
    Mellén, Anders
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Petersen, Astrid H.
    Novo Nordisk A/S, Copenhagen, Denmark.
    Dahl, Ulf L.
    Novo Nordisk A/S, Copenhagen, Denmark.
    Wollmer, Per
    Lund University, Lund, Sweden.
    The impact of smoking on inhaled insulin2003In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 26, no 3, p. 677-682Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: This study, one of the first to address issues of pulmonary insulin delivery in smokers, compared pharmacokinetics of inhaled insulin delivered via the AERx insulin Diabetes Management System (iDMS) in nondiabetic cigarette smokers and nonsmokers.

    RESEARCH DESIGN AND METHODS: In this randomized two-period crossover efficacy and safety trial in 27 nondiabetic smokers and 16 nonsmokers (18 men/25 women, mean age 28 years, mean BMI 23.0 kg/m(2)), subjects received single doses of inhaled insulin (33.8 IU) following overnight fasting on consecutive dosing days. On one dosing day, smokers smoked three cigarettes immediately before insulin administration ("acute smoking"); on the other dosing day, smokers had not smoked since midnight ("nonacute smoking"). After inhalation, 6-h serum insulin and serum glucose profiles were determined.

    RESULTS: Pharmacokinetic results for evaluable subjects were derived from serum insulin profiles. The amount of insulin absorbed during the first 6 h after dosing (area under the exogenous serum insulin curve from 0 to 6 h [AUC((0-6 h))]) was significantly greater in smokers (63.2 vs. 40.0 mU l(-1) x h(-1), P = 0.0017); peak concentration was both higher and earlier in the smokers (maximal serum concentration of insulin [C(max)] 42.0 vs. 13.9 mU/l, P < 0.0001; time to maximal serum concentration of insulin [t(max)] 31.5 vs. 53.9 min, P = 0.0003). The estimated intrasubject variability of AUC((0-6 h)) was 13.7 and 16.5% for nonsmokers and smokers, respectively. No safety issues arose.

    CONCLUSIONS: Absorption of inhaled insulin via the AERx iDMS was significantly greater in smokers, with a higher AUC((0-6 h)) and C(max) and a shorter t(max). Intrasubject variability of AUC((0-6 h)) was low and similar in nonsmokers and smokers. These data prompt more extensive investigation of inhaled insulin in diabetic smokers.

  • 22.
    Home, P. D.
    et al.
    Institute of Cellular Medicine, Diabetes, Newcastle University, Newcastle upon Tyne, UK.
    Meneghini, L.
    Miller School of Medicine, University of Miami, Miami FL, USA.
    Wendisch, U.
    Gemeinschaftspraxis für Innere Medizin und Diabetologie, Hamburg, Germany.
    Ratner, R. E.
    MedStar Health Research Institute, Hyattsville MD, USA.
    Johansen, T.
    Novo Nordisk A ⁄ S, Søborg, Denmark.
    Christensen, T. E.
    Novo Nordisk A ⁄ S, Søborg, Denmark.
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Endocrine and Diabetes Centre, Karlstad Hospital, Karlstad, Sweden.
    Roberts, A. P.
    Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide SA, Australia.
    Birkeland, K. I.
    Faculty of Medicine, Department of Endocrinology, Oslo University Hospital, University of Oslo, Oslo, Norway.
    Improved health status with insulin degludec compared with insulin glargine in people with Type 1 diabetes2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 6, p. 716-720Article in journal (Refereed)
    Abstract [en]

    Aims: The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed.

    Methods: Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains.

    Results: At study end, HbA1c reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.250.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.521.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.325.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.8914.18)] and mental health domains [+2.46 (95% CI 0.104.82)]. For mental component score, Cohens effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI 2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine.

    Conclusions: In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.

  • 23.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Diabetes Melitus: Typ 1-diabetes, Typ 2-diabetes2016In: FYSS 2017: Fysisk aktivitet i sjukdomsprevention och sjukdomsbehandling / [ed] Maria Hagströmer, Eva Jansson, Stockholm: Läkartidningen Förlag AB , 2016, 3, p. 371-390Chapter in book (Refereed)
  • 24.
    Jendle, Johan
    Endocrine and Diabetes Centre, Central Hospital, Karlstad, Sweden; Faculty of Health Sciences, Örebro University Hospital, Örebro, Sweden.
    Resource utilisation and costs for the treatment of diabetes in the developed world: an economical burden that needs to be solved2009In: International journal of clinical practice (Esher), ISSN 1368-5031, E-ISSN 1742-1241, Vol. 63, no 7, p. 980-982Article in journal (Refereed)
  • 25.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Adolfsson, Peter
    Department of Pediatrics, Hospital of Halland, Kungsbacka, Sweden; Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Continuous Glucose Monitoring Diving and Diabetes: An Update of the Swedish Recommendations2019In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968Article in journal (Refereed)
    Abstract [en]

    Divers travel to different countries to explore various diving sites worldwide. In 2005, the Divers Alert Network (DAN) published their guidelines for recreational diving and diabetes mellitus. However, although years have passed, there is still no consensus in the form of international guidelines on diabetes and diving. Large differences are noted with regard to the regulations in different countries. Furthermore, the diabetes technology has evolved rapidly and is not reflected in current international guidelines. This is potentially both a medical and an insurance problem for a diver with diabetes. We present a short summary of the recently updated Swedish recommendations for recreational divers with type 1 diabetes mellitus, focusing on the use of continuous glucose monitoring and continuous subcutaneous insulin infusion during such circumstances.

  • 26.
    Jendle, Johan
    et al.
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Department of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Adolfsson, Peter
    Pediatric Growth Research Center, Department of Pediatrics, Institute for the Health of Women and Children, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Impact of high altitudes on glucose control2011In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 5, no 6, p. 1621-1622Article in journal (Refereed)
  • 27.
    Jendle, Johan
    et al.
    Endokrin- och diabetescentrum, Karlstad, Sweden.
    Adolfsson, Peter
    Drottning Silvias barn- och ungdomssjukhus, Göteborg, Sweden.
    Attvall, Stig
    Diabetescentrum, Sahlgrenska universitetssjukhuset, Sahlgrenska, ­Göteborg, Sweden.
    Örnhagen, Hans
    Svenska sportdykarförbundet, Stockholm, Sweden.
    Dykning vid diabetes möjligt men inte riskfritt [Diving in diabetes possible but not without risks]2011In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 108, no 44, p. 2230-2231Article in journal (Refereed)
  • 28.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Endocrine and Diabetes Centre, Karlstad Hospital, Karlstad, Sweden.
    Adolfsson, Peter
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden .
    Ornhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Swedish recommendations on recreational diving and diabetes mellitus2012In: Diving and Hyperbaric Medicine, ISSN 1833-3516, Vol. 42, no 4, p. 231-233Article in journal (Refereed)
    Abstract [en]

    Divers from many countries travel to explore various diving sites worldwide. In 2005, the Divers Alert Network (DAN) wrote guidelines for recreational diving and diabetes mellitus, but there is no up-to-date consensus or adoption of international guidelines on diabetes and diving. There are also large differences between the regulations in different countries. This is potentially both a medical and an insurance problem for a diver with diabetes. We present the current Swedish recommendations for recreational divers with Type 1 diabetes mellitus.

  • 29.
    Jendle, Johan
    et al.
    Endokrin-och Diabetescentrum, Centralsjukhuset, Karlstad, Sweden.
    Alvarsson, Michael
    Kliniken för endokrionologi, metabolism och diabetes, Karolinska universitetssjukhuset, Solna, Sweden.
    Hanås, Ragnar
    Barn- och ungdomskliniken, NU-sjukvården, Uddevalla, Sweden.
    Attvall, Stig
    Diabetescentrum, SU sahlgrenska, Göteborg, Sweden.
    Mätning av blodketoner[Measuring blood ketones]: när, var och hur[when, where and how]2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 45, p. 2031-2032Article in journal (Refereed)
  • 30.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Birkenfeld, A. L.
    Department of Medicine III, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany; Paul Langerhans Institute Dresden, Helmholtz Center Munich at Technische Universität Dresden, Dresden, Germany.
    Polonsky, W. H.
    Behavioral Diabetes Institute, University of California San Diego, San Diego, CA, USA.
    Silver, R.
    Southern New Hampshire Diabetes and Endocrinology, Nashua, NH, USA.
    Uusinarkaus, K.
    DaVita Medical Group, University of Colorado School of Medicine, Colorado Springs, CO, USA.
    Hansen, T.
    Novo Nordisk A/S, Søborg, Denmark.
    Håkan-Bloch, J.
    Novo Nordisk A/S, Søborg, Denmark.
    Tadayon, S.
    Novo Nordisk A/S, Søborg, Denmark.
    Davies, M. J.
    University of Leicester, Diabetes Research Centre, Leicester, UK.
    Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials2019In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 21, no 10, p. 2315-2326Article in journal (Refereed)
    Abstract [en]

    AIM: To investigate treatment satisfaction with semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, versus placebo/active comparators in theSUSTAIN clinical trial programme.

    METHODS: In SUSTAIN 2-5 and 7, the Diabetes Treatment Satisfaction Questionnaire was used to evaluate patient-perceived treatment satisfaction, hyperglycaemia and hypoglycaemia. Post hoc subgroup analyses were conducted to explore the effects of gastrointestinal adverse events (GI AEs), weight loss (>= 5%) or achieving glycaemic (HbA1c < 7%) targets on treatment satisfaction.

    RESULTS: Overall treatment satisfaction increased from baseline to end of treatment with all treatments across trials. Improvements were significantly greater with semaglutide versus comparators/placebo in SUSTAIN 2-5 (all P < 0.05), and generally greater in patients who achieved versus did not achieve weight loss and glycaemic targets, often with greater improvements with semaglutide 1.0 mg versus comparator/placebo in both weight loss groups. In SUSTAIN 7, improvements in overall treatment satisfaction were generally similar between semaglutide and dulaglutide, irrespective of weight loss or glycaemic control. In SUSTAIN 7, changes in overall treatment satisfaction score were generally lower in patients with versus without GI AEs at week 16 (except dulaglutide 0.75 mg), but similar by week 40. Perceived hyperglycaemia was significantly reduced from baseline to end of treatment with semaglutide versus all comparators/placebo (all P < 0.05). No differences between treatments were observed for perceived hypoglycaemia.

    CONCLUSIONS: Semaglutide was associated with significantly greater (SUSTAIN 2-5) or similar (SUSTAIN 7) improvements in overall treatment satisfaction versus comparators/placebo. Improvements in overall treatment satisfaction were generally greater in patients achieving versus not achieving treatment targets. Clinicaltrials.gov: NCT01930188 (SUSTAIN 2), NCT01885208 (SUSTAIN 3), NCT02128932 (SUSTAIN 4), NCT02305381 (SUSTAIN 5) and NCT02648204 (SUSTAIN 7). EudraCT: 2012-004827-19 (SUSTAIN 2), 2012-004826-92 (SUSTAIN 3), 2013-004392-12 (SUSTAIN 4), 2013-004502-26 (SUSTAIN 5) and 2014-005375-91 (SUSTAIN 7).

  • 31.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Birkenfeld, A. L.
    Technical University Dresden, Dresden, Germany.
    Silver, R.
    Southern New Hampshire Diabetes and Endocrinology, Nashua NH, USA.
    Uusinarkaus, K.
    CSHP / DaVita Clinical Research, Colorado Springs CO, USA.
    Højbjerre, L.
    Novo Nordisk A/S, Søborg, Denmark.
    Thomsen, H. F.
    Novo Nordisk A/S, Søborg, Denmark.
    Davies, M.
    Diabetes Research Centre, University of Leicester, Leicester, UK.
    Effect of Gastrointestinal Adverse Events on Treatment Satisfaction in Semaglutide Treatment of Type 2 Diabetes2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 9, p. A484-A484Article in journal (Other academic)
  • 32.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Endocrine and Diabetes Center, University of Örebro, Örebro, Sweden.
    Blonde, L.
    Ochsner Medical Center, New Orleans LA, USA.
    Rosenstock, J.
    Dallas Diabetes and Endocrine Center, Dallas, USA.
    Woo, V.
    University of Manitoba, Winnipeg, Canada.
    Gross, J.
    Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
    Jiang, H.
    Eli Lilly and Company, Indianapolis, USA.
    Milicevic, Z.
    Eli Lilly and Company, Vienna, Austria.
    Better glycaemic control and less weight gain with once weekly dulaglutide vs bedtime insulin glargine, both combined with thrice daily lispro, in type 2 diabetes (AWARD-4)2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no Suppl 1, p. S23-S24Article in journal (Other academic)
    Abstract [en]

    Background and aims: This 52 week, parallel-arm, open-label, phase 3 study compared two doses of the once weekly GLP-1 receptor agonist dulaglutide (DU) versus bedtime insulin glargine, all combined with pre-meal insulin lispro with or without metformin, in patients with type 2 diabetes mellitus inadequately controlled on conventional insulin therapy. Insulin glargine and insulin lispro were titrated to attempt to reach glycaemic targets.

    Materials and methods: Patients (N = 884; mean baseline characteristics: age 59.4 years; duration of diabetes 12.7 years; HbA1c 8.5%; body weight 91.1 kg; BMI 32.5 kg/m2; total daily insulin dose 56 U) were randomised (1:1:1) to once weekly DU 1.5 mg, DU 0.75 mg, or bedtime insulin glargine titrated-to-target. The primary objective was to compare the change in HbA1c from baseline of DU 1.5 mg with insulin glargine at 26 weeks for noninferiority (margin 0.4%) and if met, then superiority was tested.

    Results: At 26 and 52 weeks, both DU doses were statistically superior to insulin glargine for HbA1c change from baseline. Insulin glargine was associ-ated with greater fasting serum glucose reduction compared with both DU doses. The mean prandial insulin doses at 26 weeks were 93 U for DU 1.5 mg, 97 U for DU 0.75 mg, and 68 U for insulin glargine. The insulin glargine dose was 65 U. Similar insulin doses were observed at 52 weeks. Body weight decreased with DU 1.5 mg and increased with DU 0.75 mg and insulin glar-gine at 52 weeks. The rate of documented symptomatic hypoglycaemia (≤3.9 mmol/L) at 52 weeks was 31.0, 35.0,and 39.9 events/patient/year for DU 1.5 mg, DU 0.75 mg, and insulin glargine, respectively. The number of severe hypoglycaemia events was 11 for DU 1.5 mg, 15 for DU 0.75 mg, and 22 for insulin glargine. Nausea, diarrhoea, and vomiting were more common with DU 1.5 mg (25.8%, 16.6%, and 12.2%, respectively) and DU 0.75 mg (17.7%, 15.7%, and 10.6%) versus insulin glargine (3.4%, 6.1%, and 1.7%).

    Conclusion: DU compared to insulin glargine, both combined with insu-lin lispro, resulted in better glycaemic control, less body weight gain, no in-creased risk of hypoglycaemia, and more common reporting of gastrointes-tinal adverse events.

  • 33.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Christensen, Jane H.
    Department of Biomedicine, Aarhus University, Aarhus, Denmark; Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark .
    Kvistgaard, Helene
    Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
    Gregersen, Niels
    Research Unit for Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
    Rittig, Søren
    Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
    Late-onset familial neurohypophyseal diabetes insipidus due to a novel mutation in the AVP gene2012In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 77, no 4, p. 586-592Article in journal (Refereed)
    Abstract [en]

    Objective: Familial neurohypophyseal diabetes insipidus (FNDI) is mainly an autosomal dominant inherited disorder presenting with severe polydipsia and polyuria in early childhood. In this study, we aimed to determine the molecular genetics and clinical characteristics of a large Swedish-Norwegian family presenting with very late-onset autosomal dominant FNDI.

    Patients: Six probands with a history of developing polyuria and polydipsia during adolescence were studied.

    Measurements: Information on family demography was collected by personal interview with family members. The genetic cause of FNDI was identified by DNA sequencing analysis of the coding regions of the AVP gene. The clinical characteristics were determined by the measurement of basal urine production and osmolality as well as by measurements of concurrent levels of plasma AVP, plasma osmolality, and urine osmolality during fluid deprivation and bolus injection of DDAVP. The integrity of the neurohypophysis was evaluated by magnetic resonance imaging.

    Results: The mean age of encountering the first clinical symptoms in the family was 14·8 years (range 3-30 years) (n = 17). All six affected subjects investigated were heterozygous for a novel mutation in the AVP gene (g.1848C>T) predicting a p.Pro84Leu substitution in the AVP precursor protein. We found partial deficiency in evoked AVP secretion during fluid deprivation in one subject and complete deficiency in another. The pituitary bright spot was absent in all six affected subjects studied.

    Conclusion: A novel mutation in the AVP gene predicted to cause a neurophysin II dimerization defect is causing surprisingly late onset of FNDI in a large, six generation, Swedish-Norwegian family. The mutation is associated with both complete and partial deficiency in evoked AVP secretion during fluid deprivation in patients who have suffered from FNDI for decades.

  • 34.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    de Portu, S.
    Roze, S.
    Cost effectiveness analysis of MiniMed 670G system versus continuous subcutaneous insulin infusion, in individuals with type 1 diabetes2019Conference paper (Other academic)
  • 35.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Edelman, S.
    University of California, School of Medicine-Division of Endocrinology and Metabolism, San Diego CA, USA.
    Dandona, P.
    State University of New York, Department of Medicine- Division of Endocrinology- Diabetes and Metabolism, BuffaloNY, USA.
    Mathieu, C.
    University of Leuven, Clinical and Experimental Endocrinology-UZ Gasthuisberg, Leuven, Belgium.
    Thoren, F. A.
    AstraZeneca, Global Medicines Development, Gothenburg, Sweden.
    Scheerer, M. F.
    AstraZeneca, Diabetes Medical Department, Wedel, Germany.
    Xu, J.
    AstraZeneca, Global Medicines Development, Gaithersburg MD, USA.
    Langkilde, A. M.
    AstraZeneca, Global Medicines Development, Gothenburg, Sweden.
    EFFECT OF ADDING DAPAGLIFLOZIN AS AN ADJUNCT TO INSULIN ON URINARY ALBUMIN-TO-CREATININE RATIO OVER 52 WEEKS IN ADULTS WITH TYPE 1 DIABETES2019In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 21, no Suppl. 1, p. A136-A137Article in journal (Other academic)
  • 36.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Edelman, S.
    Dandona, P.
    Mathieu, C.
    Thoren, F.A.
    Scheerer, J.
    Xu, J.
    Langkilde, A.M.
    Dapagliflozin as an adjunct to insulin on urinary albumin-to creatinine ratio over 52 weeks in adults with type 1 diabetes2019Conference paper (Other academic)
  • 37.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Ericsson, Åsa
    Novo Nordisk Scandinavia AB, Malmö, Sweden.
    Hunt, Barnaby
    Ossian Health Economics and Communications GmbH, Basel, Switzerland.
    Valentine, William J.
    Ossian Health Economics and Communications GmbH, Basel, Switzerland.
    Pollock, Richard F.
    Ossian Health Economics and Communications GmbH, Basel, Switzerland.
    Achieving Good Glycemic Control Early After Onset of Diabetes: A Cost-Effectiveness Analysis in Patients with Type 1 Diabetes in Sweden2018In: Diabetes Therapy, ISSN 1869-6953, E-ISSN 1869-6961, Vol. 9, no 1, p. 87-99Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Sweden has amongst the highest incidence rates of type 1 diabetes (T1D) in Europe. The high incidence and chronic nature of T1D result in high prevalence and economic burden. Improving glycemic control reduces the incidence of microvascular complications, which in turn reduces medical costs. The present study aimed to quantify the reductions in cost and improvements in quality-adjusted life expectancy with varying reductions in HbA1c in the T1D population.

    METHODS: The IQVIA CORE Diabetes Model was used to simulate a typical Swedish population of patients with T1D experiencing HbA1c reductions from 0.1% to 0.8% (in 0.1% increments) from 7.9% at baseline. Analyses were conducted in simulated cohorts based on data from the Swedish National Diabetes Register (NDR) and in subgroups by sex, smoking status, and body mass index (BMI), with different sets of quality-of-life utilities included. Generalized least squares (GLS) models were used to test for significant differences between subgroups. Analyses were also performed to investigate the effect of the duration of HbA1c control. Analyses were run over 50 years and outcomes discounted at 3% per annum.

    RESULTS: In the reference case analysis, reducing HbA1c lowered the incidence of microvascular and macrovascular complications and improved quality-adjusted life expectancy. GLS models identified a significantly larger benefit of reducing HbA1c in women over men, but found no significant differences in the magnitude of quality of life improvements with decreasing HbA1c when segregating by smoking status or BMI.

    CONCLUSIONS: Reducing HbA1c in a population with T1D would reduce the incidence of microvascular complications, improve life expectancy and quality of life. Larger quality-of-life benefits were observed in younger and female adult patients, but no notable differences were observed in the benefits of glycemic control in smokers versus non-smokers or in patients with low or high BMI.

  • 38.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Fang, X.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bojö, L.
    Central Hospital, Karlstad, Sweden.
    Nilsson, B.K.
    Central Hospital, Karlstad, Sweden.
    Hedberg, F.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Santos-Pardo, I.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Nyström, T.
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
    Effects on repetitive 24-hour ambulatory blood pressure in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment both in combination with metformin: A randomized open parallel-group study2018In: Journal of the American Society of Hypertension : JASH, ISSN 1933-1711, E-ISSN 1878-7436, Vol. 12, no 5, p. 346-355Article in journal (Refereed)
    Abstract [en]

    In this post hoc study, we aimed to investigate liraglutide treatment on repetitive 24-hour blood pressure (BP) in patients with type II diabetes. Sixty-two individuals with type II diabetes (45 males) were randomized to 1.8 mg liraglutide once daily or 4 mg glimepiride together with 1 g metformin twice daily. Ambulatory 24-hour systolic and diastolic blood pressure (sBP/dBP) was repetitively measured at baseline, 2 weeks, and 18 weeks. Outcomes were evaluated as treatment change from baseline, 2 weeks, and 18 weeks. Baseline clinical characteristics of liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. No statistically significant difference in 24-hour sBP/dBP between three time periods and groups was observed. There was no treatment change for 24-hour sBP at week 2 or after week 18. There was a transient treatment change in 24-hour dBP in the liraglutide group at week 2 (3.2 ± 5.4 vs. -1.2 ± 4.5 mm Hg, P < .01). A treatment change in 24-hour heart rate at week 2 (4.9 ± 6.8 vs. 1.0 ± 6.0 bpm, P = .03) and at week 18 (5.9 ± 7.8 vs. 0.2 ± 6.3 bpm, P < .01) was observed in the liraglutide group. In conclusion, liraglutide treatment did not lower BP. However, a small diurnal variation in dBP without affecting BP variability or nocturnal BP dipping was observed.

  • 39.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Grunberger, George
    Grunberger Diabetes Institute, Bloomfield Hills, USA.
    Blevins, Thomas
    Texas Diabetes and Endocrinology, Austin, USA.
    Giorgino, Francesco
    University Bari Aldo Moro, Bari, Italy.
    Hietpas, Ryan T.
    Eli Lilly and Company, Indianapolis, USA.
    Botros, Fady T.
    Eli Lilly and Company, Indianapolis, USA.
    Efficacy and Safety of Dulaglutide in the Treatment of Type 2 Diabetes: A Comprehensive Review of the Dulaglutide Clinical Data Focusing on the AWARD Phase 3 Clinical Trial Program2016In: Diabetes/Metabolism Research Reviews, ISSN 1520-7552, E-ISSN 1520-7560, Vol. 32, no 8, p. 776-790Article, review/survey (Refereed)
    Abstract [en]

    Dulaglutide (DU) is a once weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved for the treatment of type 2 diabetes mellitus (T2DM). Glycaemic efficacy and safety characteristics of DU have been assessed in six Phase 3 studies in the AWARD program. The objective of this review article is to summarise these results from the 6 completed AWARD studies. At the primary endpoint, in 5 of the 6 studies, once weekly dulaglutide 1.5 mg was superior to the active comparator (exenatide, insulin glargine [two studies], metformin, and sitagliptin), with a greater proportion of patients reaching glycated haemoglobin A1c (HbA1c) targets of <7.0% (53.0 mmol/mol) and ≤6.5% (47.5 mmol/mol). Dulaglutide 1.5 mg was non-inferior to liraglutide in AWARD-6. Once weekly dulaglutide 0.75 mg was evaluated in 5 of these trials and demonstrated superiority to the active comparator in 4 of 5 AWARD studies (exenatide, glargine, metformin, and sitagliptin), and non-inferiority to glargine in the AWARD-2 study. Similar to other GLP-1 RAs, treatment with dulaglutide was associated with weight loss or attenuation of weight gain and low rates of hypoglycaemia when used alone or with non-insulin-secretagogue therapy. The most frequently reported adverse events were gastrointestinal, including nausea, diarrhoea, and vomiting. The incidence of dulaglutide antidrug antibody formation was 1%-2.8% with rare injection site reactions. In conclusion, dulaglutide is an effective treatment for T2DM and has an acceptable tolerability and safety profile.

  • 40.
    Jendle, Johan H.
    et al.
    Örebro University, School of Medical Sciences.
    Rawshani, Araz
    Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; National Diabetes Register, Centre of Registers, Gothenburg, Sweden.
    Svensson, Ann-Marie
    Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; National Diabetes Register, Centre of Registers, Gothenburg, Sweden.
    Avdic, Tarik
    National Diabetes Register, Centre of Registers, Gothenburg, Sweden.
    Gudbjörnsdóttir, Soffia
    Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden; National Diabetes Register, Centre of Registers, Gothenburg, Sweden.
    Indications for Insulin Pump Therapy in Type 1 Diabetes and Associations With Glycemic Control2016In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 10, no 5, p. 1027-1033Article in journal (Refereed)
    Abstract [en]

    Background: Real-world data regarding indications for use of insulin pump remain sparse. We investigated characteristics among individuals with type 1 diabetes (T1D) in relation to indication for use of insulin pump (CSII). Comparison was made with T1D subjects using multiple daily injections (MDI).

    Methods: We included all individuals with T1D who had at least 1 registration in the National Diabetes Register during 2014-2015. Among 46 874 individuals, we excluded 2350 due to missing data. We examined 35 725 on MDI and 8799 on CSII regarding characteristics in relation to insulin delivery method, as well as association between insulin delivery and glycemic control (HbA1c) and presence of albuminuria.

    Results: Unadjusted mean (SD) HbA1c was 63.84 (15.07) mmol/mol (7.99 [1.38]%) and 63.75 (13.19) mmol/mol (7.99 [1.21]%) in the MDI and CSII group, respectively. MDI and CSII users were on average 48.8 and 41.5 years old, respectively. MDI users were on average 26 years old and CSII users 17 years old at the time of diabetes diagnosis. Overall, a higher proportion of CSII users were females (53.5%). As compared with MDI, use of CSII was associated with up to 7.84 mmol/mol (0.72%) lower HbA1c in a multivariable adjusted model. Use of CSII was, however, not associated with risk of having albuminuria.

    Conclusions: CSII was used more frequently in younger individuals, early-onset diabetes, and problematic glycemic control. The use of CSII was associated with lower HbA1c among CSII users except from those who started CSII due to high HbA1c.

  • 41.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Heinemann, Lutz
    Science and Co, Neuss, Germany.
    Real-Time Continuous Glucose Monitoring Usage in Pilots with Diabetes: An Option to Improve Safety2018In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 20, no 7, p. 453-454Article in journal (Other academic)
  • 42.
    Jendle, Johan
    et al.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlberg, B. E.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Effects of intrapulmonary insulin in patients with non-insulin-dependent diabetes1996In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 56, no 6, p. 555-561Article in journal (Refereed)
    Abstract [en]

    The effects of intrapulmonary insulin administration in non-insulin-dependent diabetes mellitus (NIDDM) were studied in 12 patients in a double-blind randomized placebo-controlled intervention study. Regular human insulin, 100 U ml-1, was given as an aerosol by oral inhalation after a 12-h fasting. A significant decrease in blood glucose concentration, from 10.2 +/- 0.5 to 6.1 +/- 0.5 mmol l-1 (p < 0.0001) and a significant rise in serum insulin concentration, from 11.2 +/- 1.8 to 28.0 +/- 2.6 mU ml-1 (p < 0.0001), was seen. Serum C-peptide levels decreased from 1.6 +/- 0.2 to 1.0 +/- 0.1 nmol l-1 (p < 0.0001). No side-effects were reported following aerosol inhalation. If similar results can be obtained when using this route for insulin administration to insulin-dependent diabetes mellitus patients, this may be a useful complement to traditional subcutaneous insulin injections in these patients.

  • 43.
    Jendle, Johan
    et al.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlberg, B. E.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Intrapulmonary administration of insulin to healthy volunteers1996In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 240, no 2, p. 93-98Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study the biological effects of nebulized insulin, administered intrapulmonary, to healthy volunteers.

    DESIGN: A double-blind, randomized, controlled intervention study.

    SETTING: The department of Internal Medicine, University Hospital, Linköping, Sweden.

    SUBJECTS: Eight healthy, non-smoking volunteers, with a mean age of 28 (range 22 to 56) years.

    INTERVENTIONS: Regular human insulin 100 U mL-1 (Actrapid) or 0.9% saline was given randomly as an oral inhalation. Insulin was given in three different doses (40, 80 and 160 U). Aerosol was generated by a new jet nebulizer.

    MAIN OUTCOME MEASURES: Blood glucose, serum insulin, and serum C-peptide.

    RESULTS: After the 160 U insulin dose the blood glucose concentration (mean +/- SE) fell from 4.3 +/- 0.2 to 2.8 +/- 0.2 mmol L-1 (P < 0.001), concomitant with an increase in mean serum insulin concentrations, rising from 9.5 +/- 1.5 to 26.1 +/- 2.5 mU L-1 (P < 0.001). Serum C-peptide concentrations simultaneously decreased from 0.48 +/- 0.03 to 0.12 +/- 0.02 mmol L-1 (P < 0.001). All changes were dose dependent. No adverse reactions were noted and no significant changes in lung function tests.

    CONCLUSIONS: Intrapulmonary insulin administration to healthy subjects can induce a significant hypoglycaemia and cause a clinically relevant increase in serum insulin concentrations. If similar results can be obtained when administering insulin to diabetic subjects, this insulin administration route can be a future complement to certain groups of patients.

  • 44.
    Jendle, Johan
    et al.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlberg, B. E.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Arborelius, M.
    Department of Clinical Physiology, Malmö General Hospital, Malmö, Sweden.
    An exploration of intrapulmonary insulin administration in anaesthetized and mechanically ventilated pigs1996In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 56, no 3, p. 251-258Article in journal (Refereed)
    Abstract [en]

    We investigated the efficacy of intrapulmonary administration of short-acting porcine insulin in anaesthetized pigs (n = 14) in a randomized intervention study. Insulin was administered by a new jet nebulizer (Maxin) in a random order at different doses, 0 (saline), 10 or 40 U. The hypoglycaemic effect was compared to control (0.9% saline). Blood glucose and serum insulin concentrations were followed at specified time intervals for 90 min. Plasma catecholamine concentrations were measured in order to estimate the concurrent stress. Nebulized insulin caused a significant decrease in blood glucose concentrations (p < 0.0001) (n = 28) at all doses used. The decrease in mean blood glucose concentration from the start of nebulization was 39 +/- 3% (mean +/- SEM), falling from 4.6 +/- 0.1 to 2.8 +/- 0.2 mmol 1(-1), with a nadir at 40 min after the 40 U insulin dose (n = 10). Serum insulin concentration rose from (mean +/- SEM) 5.2 +/- 0.1 to 25 +/- 9 mU 1(-1) after the insulin dose of 40 U (n = 10), the peak value occurred at 30 min. The plasma catecholamine concentrations increased significantly (p < 0.0001) (n = 28) from 0 to 60 min, this increase was similar for control and for different insulin doses. We conclude that intrapulmonary administration of insulin can cause a significant decrease in blood glucose concentrations in anaesthetized and mechanically ventilated pigs and results in clinically relevant serum insulin levels. Similar effects in humans would make inhaled insulin possible for clinical use.

  • 45.
    Jendle, Johan
    et al.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Karlberg, Bengt E.
    Department of Internal Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Persliden, Jan
    Department of Radiation Physics, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Franzén, Lennart
    Department of Pathology, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Arborelius, Måns
    Department of Clinical Physiology, Malmö General Hospital, Malmö, Sweden.
    Delivery and Retention of an Insulin Aerosol Produced by a New Jet Nebulizer1995In: Journal of Aerosol Medicine, ISSN 0894-2684, E-ISSN 1557-9026, Vol. 8, no 3, p. 243-254Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: This study describes the delivery and distribution of an aerosol generated by a jet nebulizer (MAXIN) in an experimental animal model. Anesthetised, intubated and ventilated piglets inhaled radiolabeled technetium diethylene-triamine-penta-acetic acid (99mTc-DTPA) through the endotracheal tube. The lungs were excised en bloc and scintigraphed, using a computerized gamma camera to evaluate the pattern of distribution. By nebulizing radiolabeled 125I-insulin and comparing the activity deposited on inspiratory and expiratory electrostatic filters, delivery and retention of nebulized insulin was assessed. The distribution of aerosol in the lungs was very even and reached the most peripheral parts. The delivery of nebulized insulin was calculated to be 88.9 +/- 5.3% and 36.1 +/- 8.8% of the insulin delivered to the respiratory tract was retained. The immediate local effects of insulin aerosol administration on the lungs were evaluated using light microscopy. No adverse effects were observed at histopathologic examination of the lung tissue.

    CONCLUSION: This study shows a high penetration of aerosol to the peripheral parts of the lung and efficient delivery of nebulized insulin when using the MAXIN-nebulizer.

  • 46.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Martin, Sherry A.
    Lilly Diabetes, Eli Lilly and Co., Indianapolis IN, USA.
    Milicevic, Zvonko
    Lilly Diabetes, Eli Lilly and Co, Vienna, Austria .
    Insulin and GLP-1 analog combinations in type 2 diabetes mellitus: a critical review2012In: Expert Opinion on Investigational Drugs, ISSN 1354-3784, E-ISSN 1744-7658, Vol. 21, no 10, p. 1463-1474Article in journal (Refereed)
    Abstract [en]

    Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists have been used in clinical management of type 2 diabetes since 2005. Currently approved agents were initially developed and approved for combination therapy with oral antidiabetic drugs (OADs). The potential for combined use with insulin has garnered increasing attention due to the potential to reduce side effects associated with insulin therapy and improve glycemic control.

    Areas covered: We reviewed published and other publicly released data from controlled and uncontrolled studies that included subjects treated with insulin/GLP-1 analog combination therapy. The currently available guidance for clinical practice when combining insulin and GLP-1 analogs was also summarized.

    Expert opinion: Limited data currently available from placebo-controlled trials support the use of exenatide twice daily or liraglutide once daily in combination with basal insulin and metformin in subjects with type 2 diabetes unable to attain treatment goals. Several randomized controlled trials are currently studying combinations of insulin with various GLP-1 analogs. Additional guidance on the clinical use of these combinations will likely be forthcoming once these studies are reported. Insulin/GLP-1 analog combinations will require optimization of blood glucose monitoring strategies and delivery systems to decrease the risk of administration errors and reduce the potential complexity of these regimens.

  • 47.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences.
    Nauck, M. A.
    Matthews, D. R.
    Frid, A.
    Hermansen, K.
    During, M.
    Zdravkovic, M.
    Strauss, B. J.
    Garber, A. J.
    Weight loss with liraglutide, a once-daily human glucagon-like peptide-1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue2009In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 11, no 12, p. 1163-1172Article in journal (Refereed)
    Abstract [en]

    Aim The effect on body composition of liraglutide, a once-daily human glucagon-like peptide-1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). Methods These were randomized, double-blind, parallel-group trials of 26 [Liraglutide Effect and Action in Diabetes-2 (LEAD-2)] and 52 weeks (LEAD-3). Patients with T2D, aged 18-80 years, body mass index (BMI) < 40 kg/m2 (LEAD-2), < 45 kg/m2 (LEAD-3) and HbA1c 7.0-11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5-2 g/day in LEAD-2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD-3. LEAD-2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD-2: adipose tissue area and hepatic steatosis were assessed. Results LEAD-2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver-to-spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD-3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). Conclusion Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.

  • 48.
    Jendle, Johan
    et al.
    Endokrin- och diabetescentrum, Centralsjukhuset i Karlstad, Karlstad, Sweden.
    Norberg, Bengt
    Endokrin- och diabetescentrum, Centralsjukhuset i Karlstad, Karlstad, Sweden.
    Kliniska erfarenheter av behandling med Levemir [Clinical experiences with Levemir treatment].2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 1-2, p. 54-54Article in journal (Refereed)
  • 49.
    Jendle, Johan
    et al.
    Örebro University, School of Medical Sciences.
    Pöhlmann, Johannes
    Ossian Health Economics and Communications GmbH, Basel, Switzerland.
    de Portu, Simona
    Medtronic International Trading Sàrl, Tolochenaz, Switzerland.
    Smith-Palmer, Jayne
    Ossian Health Economics and Communications GmbH, Basel, Switzerland.
    Roze, Stéphane
    HEVA HEOR, Lyon, France.
    Cost-Effectiveness Analysis of the MiniMed 670G Hybrid Closed-Loop System Versus Continuous Subcutaneous Insulin Infusion for Treatment of Type 1 Diabetes2019In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 21, no 3, p. 110-118Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Hybrid closed-loop (HCL) systems combine continuous glucose monitoring with continuous subcutaneous insulin infusion (CSII) to continuously self-adjust basal insulin delivery. Relative to CSII, HCL improves glycemic control and reduces the risk of hypoglycemia but has higher acquisition costs. The aim of this analysis was to assess the cost-effectiveness of the MiniMed™ 670G HCL system versus CSII in people with type 1 diabetes (T1D) in Sweden.

    METHODS: Cost-effectiveness analysis, from a societal perspective, was performed over patient lifetimes using the IQVIA CORE Diabetes Model. Clinical data were sourced from a study comparing the MiniMed 670G system with CSII in people with T1D. Cost data, expressed in 2018 Swedish krona (SEK), were obtained from Swedish reference prices and published literature.

    RESULTS: The MiniMed 670G system was associated with a quality-adjusted life-year (QALY) gain of 1.90 but higher overall costs versus CSII, leading to an incremental cost-effectiveness ratio (ICER) of SEK 164,236 per QALY gained. Use of the HCL system resulted in a lower cumulative incidence of diabetes-related complications. Higher HCL system acquisition costs were partially offset by reduced complication costs and productivity losses. In people with T1D poorly controlled at baseline, the MiniMed 670G system was associated with 2.25 incremental QALYs versus CSII, yielding an ICER of SEK 15,830 per QALY gained.

    CONCLUSIONS: The MiniMed 670G system was associated with clinical benefits and quality-of-life improvements in people with T1D relative to CSII. At a willingness-to-pay threshold of SEK 300,000 per QALY gained, this HCL system likely represents a cost-effective treatment option for people with T1D in Sweden.

  • 50.
    Jendle, Johan
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ridderstrale, M.
    Steno Diabetes, Gentofte, Denmark.
    Jensen, H. H.
    Incentive, Holte, Denmark.
    Bøgelund, M.
    Incentive, Holte, Denmark..
    Jensen, M. M.
    Novo Nordisk, Copenhagen, Denmark.
    Ericsson, A.
    Novo Nordisk Scandinavia AB, Malmö, Sweden.
    Evans, M.
    University Hospital Llandough, Cardiff, UK.
    Investigating the short-term impact of poor glycemic control on the daily lives of people with type 2 diabetes2015In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 18, no 3, p. A65-A65Article in journal (Other academic)
12 1 - 50 of 82
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