Heise T.,Profil Institute For Stoffwechselforschung |
Tack C.J.,Radboud University Nijmegen |
Cuddihy R.,International Diabetes Center |
Davidson J.,University of Texas at Dallas |
And 6 more authors.
Diabetes Care | Year: 2011
OBJECTIVE - Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the novel basal analog insulin degludec (IDeg: 70%) and insulin aspart (IAsp: 30%). We compared the safety and efficacy of IDegAsp, an alternative formulation (AF) (55%IDeg and 45% IAsp), and insulin glargine (IGlar) in insulin-naïve subjects with type 2 diabetes inadequately controlled with oral antidiabetic drugs. RESEARCH DESIGN AND METHODS - In this 16-week, open-label trial, subjects (mean age 59.1 years, A1C 8.5%, BMI 30.3 kg/m 2) were randomized to once-daily IDegAsp (n = 59), AF (n = 59), or IGlar (n = 60), all in combination with metformin. Insulin was administered before the evening meal and dose-titrated to a fasting plasma glucose (FPG) target of 4.0-6.0 mmol/L. RESULTS - After 16 weeks, mean A1C decreased in all groups to comparable levels (IDegAsp: 7.0%; AF: 7.2%; IGlar: 7.1%). A similar proportion of subjects achieved A1C <7.0% without confirmed hypoglycemia in the last 4 weeks of treatment (IDegAsp: 51%; AF: 47%; IGlar: 50%). Mean 2-h postdinner plasma glucose increase was lower for IDegAsp (0.13 mmol/L) and AF (0.24mmol/L) than IGlar (1.63 mmol/L), whereasmean FPG was similar (IDegAsp: 6.8mmol/L; AF: 7.4 mmol/L; IGlar: 7.0 mmol/L). Hypoglycemia rates were lower for IDegAsp and IGlar than AF (1.2, 0.7, and 2.4 events/patient year). Nocturnal hypoglycemic events occurred rarely for IDegAsp (1 event) and IGlar (3 events) compared with AF (27 events). CONCLUSIONS - In this proof-of-concept trial, once-daily IDegAsp was safe, well tolerated, and provided comparable overall glycemic control to IGlar at similar low rates of hypoglycemia, but better postdinner plasma glucose control. © 2011 by the American Diabetes Association.
Ahmad S.,Center for Diabetes and Metabolism |
Chowdhury T.A.,Center for Diabetes and Metabolism |
Chowdhury T.A.,Royal London Hospital |
Boucher B.J.,Center for Diabetes and Metabolism
Journal of Diabetes and its Complications | Year: 2013
Diabetes and cancer are common diseases that may co-exist in the same individual. There is significant evidence that patients with diabetes have increased risk of developing certain cancers, especially colorectal, pancreatic and primary hepatic cancer. There is also good evidence that low levels of vitamin D are associated with increased risk of diabetes and increased risk of colorectal, and possibly other, cancers. In this article we propose that low levels of vitamin D may increase the risk of cancer in people with diabetes and describe potential molecular pathways. We suggest that large scale randomised trials of vitamin D supplementation in patients at risk of diabetes, and in patients with established diabetes to examine the effect on cancer risk, are required. © 2013 Elsevier Inc. All rights reserved.
A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: Results from continuous glucose monitoring in a proof-of-concept trial
Liebl A.,Center for Diabetes and Metabolism |
Davidson J.,University of Texas at Dallas |
Mersebach H.,Novo Nordisk AS |
Dykiel P.,Novo Nordisk AS |
And 2 more authors.
Journal of Diabetes Science and Technology | Year: 2013
Purpose: Insulin degludec coformulated with insulin aspart (as IDegAsp) can cover 24 h basal insulin and postprandial insulin requirements after a main meal with one injection. We compared glycemic stability following IDegAsp or insulin glargine (IGlar) given before the evening meal in patients with type 2 diabetes. Methods: A subset of 112 insulin-naïve type 2 diabetes patients from a randomized, parallel-group trial (IDegAsp versus IGlar, each added to metformin) underwent 72 h continuous interstitial glucose (IG) monitoring after 16 weeks of treatment. End points included mean IG concentrations, 2 h postprandial IG increments and postprandial peak, IG fluctuation (summed area above and below mean IG), within-subject coefficient of variation (day-to-day variation) in mean nocturnal IG, and episodes of low (<3.5 mmol/liter) and high (>10 mmol/liter) IG. Values were derived for the entire 72 h, with the nocturnal interval (0001-0559 h) also assessed. Results: The postdinner IG increment observed with IGlar did not occur with IDegAsp [IDegAsp - IGlar, -1.42 (-2.15, -0.70) mmol/liter]. Nocturnal IG fluctuation was 21% lower with IDegAsp [IDegAsp/IGlar, 0.79 (0.66, 0.96) mmol/liter], with 48% fewer nocturnal high IG episodes [ratio IDegAsp/IGlar, 0.52 (0.32, 0.87)]. Conclusions: IDegAsp given with the evening meal reduces postdinner glucose excursion and provides more stable nocturnal glycemia as compared with IGlar. © Diabetes Technology Society.
News Article | October 24, 2016
Northwestern Medicine scientists have discovered circadian clocks in muscle tissue that control the muscle's metabolic response and energy efficiency depending on the time of day. The finding in mice sheds light on the time-of-day differences in muscle's ability to adapt to exercise and use oxygen for energy. Muscle cells are more efficient during an organism's normal waking hours, the study found. All cells in the body, including those in muscle, contain a clock that regulates how cells adapt to changes in the environment and activity across the 24-hour day. "Oxygen and the internal clock are doing a dance together inside muscle cells to produce energy, and the time of day determines how well that dance is synchronized," said senior author Dr. Joseph Bass. "The capacity for a cell to perform its most important functions, to contract, will vary according to the time of day." More research is needed before the finding can be translated into workout advice. "We're not saying we can tell athletes when they should work out," Bass said, "but in the future, perhaps, you may be able to take advantage of these insights to optimize muscle function." Bass is the Northwestern Medicine chief of endocrinology, metabolism and molecular medicine, and director of the Center for Diabetes and Metabolism at Northwestern University Feinberg School of Medicine. He also is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Clara Bien Peek, the first author and a research assistant professor, spearheaded the work on muscle and timing. The paper has been published in the journal Cell Metabolism. The research has implications beyond muscle cells because oxygen response is important in all cells. In particular, the deprivation of oxygen is a key factor in heart attacks and in cancer, in which the depletion of oxygen curiously enables cancer cells to grow. In the research, scientists performed studies in mice, which were exercised on a treadmill at different times of day, as well as in isolated muscle fibers in which the circadian clock was genetically mutated. The scientists analyzed mouse muscle tissues and muscle fibers for expression of genes that are important for exercise. In this way, they determined the impact of deregulation of the circadian clock on muscle fibers in terms of how muscle processes fuel, like sugar and fat, when oxygen levels are low. "When we manipulated the clock genetically, we noticed there were profound abnormalities in the muscle," Bass said. "That set us on a course to understand how the inner muscle clock is important in regulating how well the muscle cell can mobilize energy." When mice, which are nocturnal, are exercised during the night, their muscles are better at turning on genes to help them adapt to exercise, scientists found. Since these genes also exist in humans, this suggests humans may also be able to respond better to exercise during the daytime. The muscle clocks control the metabolic response by interacting with proteins called HIFs that change metabolism when oxygen concentrations get too low in order to allow muscle cells to continue to make energy. Normally when we rest or do low-level exercise, our muscles consume oxygen to make energy. When we start to sprint or exercise strenuously, we consume oxygen faster and quickly run out. That's when the dip in oxygen triggers HIFs and signals muscles to switch to sugar for energy - which in turn increases lactic acid. Turning off the muscle clock prevented the normal capacity of exercise to induce sugar consumption and generation of lactic acid. These findings suggest that better exercise capacity may be tied to specific times of day. "In the future, we may discover new ways to manipulate the oxygen response of the cell by resetting the clock," said Bass, who also holds the Charles F. Kettering Professorship of Medicine at Feinberg. He noted drugs are available that can manipulate the internal clock in cells. "If we can optimize muscle function, " he said, "it's also a critical step in understanding how to impact glucose metabolism in diabetes." Diabetes is characterized by a failure of muscle to consume glucose, which in turn controls blood sugar levels. Strengthening the muscle clock may provide a new way to eliminate excess glucose and treat diabetes. The scientists tested their theories about the internal clock in muscle cells because those cells are particularly dependent on oxygen for contraction and metabolism. "We wanted to determine the rules that interconnect clocks with the physiological use of oxygen," Bass said. "We believe that studying muscle can provide us with the rules of how clocks govern response to oxygen, and we would like to test these principles in a variety of conditions." The study was supported by National Institutes of Health grants R01DK090625, R01DK100814 and K01DK105137-02 from the National Institute of Diabetes and Digestive and Kidney Diseases and grant P01AG011412 from the National Institute on Aging. Lynn Sage Cancer Research Foundation and others also supported the study. Article: Circadian Clock Interaction with HIF1α Mediates Oxygenic Metabolism and Anaerobic Glycolysis in Skeletal Muscle, Clara Bien Peek, Daniel C. Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J. Tsai, Nicolle A. Bonar, Maureen R. McNulty, Kathryn Moynihan Ramsey, Joseph Bass, Cell Metabolism, doi: 10.1016/j.cmet.2016.09.010, published 20 October 2016.
Christiansen J.S.,Aarhus University Hospital |
Liebl A.,Center for Diabetes and Metabolism |
Davidson J.A.,University of Texas Southwestern Medical Center |
Ligthelm R.J.,EHM Clinic |
Halimi S.,Grenoble University Hospital Center
Diabetes, Obesity and Metabolism | Year: 2010
Some patients with type 2 diabetes continue to have high postprandial blood glucose levels on twice-daily regimens of 'low-ratio' premix insulin formulations (up to 30% rapid-acting, with 70% protracted insulin). These patients require intensified insulin therapy, which can be provided by a twice- or thrice-daily regimen of mid-ratio (50% rapid-acting and 50% protaminated intermediate-acting insulin - human or analogue) or high-ratio (70% rapid-acting and 30% protaminated insulin - analogue only) premix insulin. Alternatively, a third daily injection of low-ratio premix insulin can be added to the regimen, with the option of incorporating one or more injections of mid- or high-ratio premix as required, and as an alternative to basal-bolus therapy. How these mid- and high-ratio formulations differ from the low-ratio premix insulins is reviewed here, with the aim of identifying the role of these formulations in diabetes management. Glucose clamp studies have shown that premix analogues give serum insulin levels proportional to their percentage of rapid-acting uncomplexed insulin: the higher the proportion, the greater the maximum level reached. Other pharmacokinetic parameters were not always significantly different between the mid- and high-ratio formulations. In clinical trials, postprandial plasma glucose and glycated haemoglobin A1c (HbA1c) levels were significantly reduced with thrice-daily mid- /high-ratio premix analogue when compared with twice-daily low-ratio biphasic human insulin (BHI) 30/70 or once-daily insulin glargine. Moreover, glycaemic control with mid-/high-ratio premix analogue was found to be similar to that with a basal-bolus therapy. Mid- and high-ratio premix regimens are generally well tolerated. The frequency of minor hypoglycaemia was reportedly higher with mid- /high-ratio premix analogues than with BHI 30, but nocturnal hypoglycaemia was less frequent. Although there is little evidence that clinical outcomes with mid-ratio premix analogues are different from those with high-ratio, they are useful additions to the low-ratio formulations for the management of diabetes, and addressing postprandial hyperglycaemia in particular. © 2009 Blackwell Publishing Ltd.
Leichter S.B.,Center for Diabetes and Metabolism |
Leichter S.B.,Mercer University |
Bowman K.,Columbus Research Foundation |
Adkins R.A.,Columbus Research Foundation |
Jelsovsky Z.,BioStat International
Diabetes Technology and Therapeutics | Year: 2013
Background: Previous studies have provided limited guidance regarding the clinical efficacy and cost-effectiveness of interventions using "telemedicine" models in the management of diabetes mellitus. We conducted a study to determine if routine clinical assessments of diabetes patients could be effectively conducted via computer and telephone interaction with patients and still provide clinical results similar to traditional office care. Subjects and Methods: We enrolled 100 subjects with diabetes in this 12-month, randomized, controlled, non-inferiority study. Subjects were randomized (1:1 ratio) to a control group (CG) or study group (SG). Baseline characteristics were similar. CG subjects participated in quarterly office visits; SG subjects participated in two office visits (months 6 and 12) and two telemedicine interactions (months 3 and 9). Changes in clinical measurements (hemoglobin A1c [HbA1c], blood pressure, lipids, body mass index [BMI], and body weight) and clinician time requirements were assessed. Results: Seventy subjects completed the study (CG, n=37; SG, n=33). No significant between-group differences in HbA1c, blood pressure, lipids, or BMI were seen at 12 months. SG subjects showed significantly greater reductions in mean (SD) body weight compared with CG subjects: -5.2 (1.6) pounds versus -0.7 (1.5) pounds, respectively (P=0.04). Clinician time requirements for SG subjects were reduced by >40%. Conclusions: Our study demonstrated that use of a telemedicine-based treatment protocol in diabetes patients is feasible and efficient and yields similar clinical outcomes compared with traditional, clinic-based protocols. Telemedicine applications of computer software can potentially expand access to care for patients and may reduce costs for patients, providers, and payers. © Mary Ann Liebert, Inc.
Liebl A.,Center for Diabetes and Metabolism |
Khunti K.,University of Leicester |
Orozco-Beltran D.,University Miguel Hernández |
Yale J.-F.,McGill University
Clinical Medicine Insights: Endocrinology and Diabetes | Year: 2015
Type 2 diabetes mellitus (T2D) is a growing healthcare burden primarily due to long-term complications. Strict glycemic control helps in preventing complications, and early introduction of insulin may be more cost-effective than maintaining patients on multiple oral agents. This is an expert opinion review based on English peer-reviewed articles (2000-2012) to discuss the health economic consequences of T2D treatment intensification. T2D costs are driven by inpatient care for treatment of diabetes complications (40%-60% of total cost), with drug therapy for glycemic control representing 18% of the total cost. Insulin therapy provides the most improved glycemic control and reduction of complications, although hypoglycemia and weight gain may occur. Early treatment intensification with insulin analogs in patients with poor glycemic control appears to be cost-effective and improves clinical outcomes. © the authors, publisher and licensee Libertas Academica Limited.
Liebl A.,Center for Diabetes and Metabolism |
Seitz L.,Novo Nordisk AS |
Palmer A.J.,Menzies Research Institute
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association | Year: 2014
BACKGROUND: A retrospective analysis of German general practice data demonstrated that insulin aspart (IA) was associated with a significantly reduced incidence of macrovascular events (MVE: stroke, myocardial infarction, peripheral vascular disease or coronary heart disease) vs. regular human insulin (RHI) in type 2 diabetes patients. Economic implications, balanced against potential improvements in quality-adjusted life years (QALYs) resulting from lower risks of complications with IA in this setting have not yet been explored.METHODS: A decision analysis model was developed utilizing 3-year initial MVE rates for each comparator, combined with published German-specific insulin and MVE costs and health utilities to calculate number needed to treat (NNT) to avoid any MVE, incremental costs and QALYs gained/ person for IA vs. RHI. A 3-year time horizon and German 3(rd)-party payer perspective were used. Probabilistic sensitivity analysis was performed, sampling from distributions of key parameters. Additional sensitivity analyses were performed.RESULTS: NNT over a 3 year period to avoid any MVE was 8 patients for IA vs. RHI. Due to lower MVE rates, IA dominated RHI with 0.020 QALYs gained (95% confidence interval: 0.014-0.025) and cost savings of EUR 1 556 (1 062-2 076)/person for IA vs. RHI over the 3-year time horizon. Sensitivity analysis revealed that IA would still be overall cost saving even if the cost of IA was double the cost/unit of RHI.CONCLUSIONS: From a health economics perspective, IA was the superior alternative for the insulin treatment of type 2 diabetes, with lower incidence of MVE events translating to improved QALYs and lower costs vs. RHI within a 3-year time horizon. © J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York.
Liebl A.,Center for Diabetes and Metabolism
Primary care diabetes | Year: 2010
The treatment of type 2 diabetes is shifting from secondary specialist centres to the primary care setting. However, for this shift to be sustainable and successful, primary care physicians (PCPs) must effectively provide aspects of diabetes care traditionally supplied by specialists. In particular, the early and appropriate use of insulin in type 2 diabetes will increasingly become the responsibility of PCPs. This review examines how patients with type 2 diabetes are currently managed across several European countries, and explores the evidence around insulin use in type 2 diabetes and the implications for primary care. 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd.. All rights reserved.
PubMed | Center for Diabetes and Metabolism
Type: Review | Journal: Primary care diabetes | Year: 2016
Increases in glycaemia, particularly following meals, have been independently associated with diabetes complications, most notably cardiovascular disease. Control of postprandial plasma glucose (PPG) therefore plays an important role in diabetes management. International diabetes guidelines acknowledge the value of PPG monitoring yet place relatively little emphasis on PPG control. This article considers the impact of suboptimal PPG control and current recommendations with regard to management of PPG. Specific consideration is given to the role of biphasic insulins, one of the treatment options recognised by the International Diabetes Federation as preferentially lowering PPG levels.