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9. A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk

Author

Manning, Alisa, primary, Highland, Heather M., additional, Gasser, Jessica, additional, Sim, Xueling, additional, Tukiainen, Taru, additional, Fontanillas, Pierre, additional, Grarup, Niels, additional, Rivas, Manuel A., additional, Mahajan, Anubha, additional, Locke, Adam E., additional, Cingolani, Pablo, additional, Pers, Tune H., additional, Viñuela, Ana, additional, Brown, Andrew A., additional, Wu, Ying, additional, Flannick, Jason, additional, Fuchsberger, Christian, additional, Gamazon, Eric R., additional, Gaulton, Kyle J., additional, Im, Hae Kyung, additional, Teslovich, Tanya M., additional, Blackwell, Thomas W., additional, Bork-Jensen, Jette, additional, Burtt, Noël P., additional, Chen, Yuhui, additional, Green, Todd, additional, Hartl, Christopher, additional, Kang, Hyun Min, additional, Kumar, Ashish, additional, Ladenvall, Claes, additional, Ma, Clement, additional, Moutsianas, Loukas, additional, Pearson, Richard D., additional, Perry, John R.B., additional, Rayner, N. William, additional, Robertson, Neil R., additional, Scott, Laura J., additional, van de Bunt, Martijn, additional, Eriksson, Johan G., additional, Jula, Antti, additional, Koskinen, Seppo, additional, Lehtimäki, Terho, additional, Palotie, Aarno, additional, Raitakari, Olli T., additional, Jacobs, Suzanne B.R., additional, Wessel, Jennifer, additional, Chu, Audrey Y., additional, Scott, Robert A., additional, Goodarzi, Mark O., additional, Blancher, Christine, additional, Buck, Gemma, additional, Buck, David, additional, Chines, Peter S., additional, Gabriel, Stacey, additional, Gjesing, Anette P., additional, Groves, Christopher J., additional, Hollensted, Mette, additional, Huyghe, Jeroen R., additional, Jackson, Anne U., additional, Jun, Goo, additional, Justesen, Johanne Marie, additional, Mangino, Massimo, additional, Murphy, Jacquelyn, additional, Neville, Matt, additional, Onofrio, Robert, additional, Small, Kerrin S., additional, Stringham, Heather M., additional, Trakalo, Joseph, additional, Banks, Eric, additional, Carey, Jason, additional, Carneiro, Mauricio O., additional, DePristo, Mark, additional, Farjoun, Yossi, additional, Fennell, Timothy, additional, Goldstein, Jacqueline I., additional, Grant, George, additional, Hrabé de Angelis, Martin, additional, Maguire, Jared, additional, Neale, Benjamin M., additional, Poplin, Ryan, additional, Purcell, Shaun, additional, Schwarzmayr, Thomas, additional, Shakir, Khalid, additional, Smith, Joshua D., additional, Strom, Tim M., additional, Wieland, Thomas, additional, Lindstrom, Jaana, additional, Brandslund, Ivan, additional, Christensen, Cramer, additional, Surdulescu, Gabriela L., additional, Lakka, Timo A., additional, Doney, Alex S.F., additional, Nilsson, Peter, additional, Wareham, Nicholas J., additional, Langenberg, Claudia, additional, Varga, Tibor V., additional, Franks, Paul W., additional, Rolandsson, Olov, additional, Rosengren, Anders H., additional, Farook, Vidya S., additional, Thameem, Farook, additional, Puppala, Sobha, additional, Kumar, Satish, additional, Lehman, Donna M., additional, Jenkinson, Christopher P., additional, Curran, Joanne E., additional, Hale, Daniel Esten, additional, Fowler, Sharon P., additional, Arya, Rector, additional, DeFronzo, Ralph A., additional, Abboud, Hanna E., additional, Syvänen, Ann-Christine, additional, Hicks, Pamela J., additional, Palmer, Nicholette D., additional, Ng, Maggie C.Y., additional, Bowden, Donald W., additional, Freedman, Barry I., additional, Esko, Tõnu, additional, Mägi, Reedik, additional, Milani, Lili, additional, Mihailov, Evelin, additional, Metspalu, Andres, additional, Narisu, Narisu, additional, Kinnunen, Leena, additional, Bonnycastle, Lori L., additional, Swift, Amy, additional, Pasko, Dorota, additional, Wood, Andrew R., additional, Fadista, João, additional, Pollin, Toni I., additional, Barzilai, Nir, additional, Atzmon, Gil, additional, Glaser, Benjamin, additional, Thorand, Barbara, additional, Strauch, Konstantin, additional, Peters, Annette, additional, Roden, Michael, additional, Müller-Nurasyid, Martina, additional, Liang, Liming, additional, Kriebel, Jennifer, additional, Illig, Thomas, additional, Grallert, Harald, additional, Gieger, Christian, additional, Meisinger, Christa, additional, Lannfelt, Lars, additional, Musani, Solomon K., additional, Griswold, Michael, additional, Taylor, Herman A., additional, Wilson, Gregory, additional, Correa, Adolfo, additional, Oksa, Heikki, additional, Scott, William R., additional, Afzal, Uzma, additional, Tan, Sian-Tsung, additional, Loh, Marie, additional, Chambers, John C., additional, Sehmi, Jobanpreet, additional, Kooner, Jaspal Singh, additional, Lehne, Benjamin, additional, Cho, Yoon Shin, additional, Lee, Jong-Young, additional, Han, Bok-Ghee, additional, Käräjämäki, Annemari, additional, Qi, Qibin, additional, Qi, Lu, additional, Huang, Jinyan, additional, Hu, Frank B., additional, Melander, Olle, additional, Orho-Melander, Marju, additional, Below, Jennifer E., additional, Aguilar, David, additional, Wong, Tien Yin, additional, Liu, Jianjun, additional, Khor, Chiea-Chuen, additional, Chia, Kee Seng, additional, Lim, Wei Yen, additional, Cheng, Ching-Yu, additional, Chan, Edmund, additional, Tai, E Shyong, additional, Aung, Tin, additional, Linneberg, Allan, additional, Isomaa, Bo, additional, Meitinger, Thomas, additional, Tuomi, Tiinamaija, additional, Hakaste, Liisa, additional, Kravic, Jasmina, additional, Jørgensen, Marit E., additional, Lauritzen, Torsten, additional, Deloukas, Panos, additional, Stirrups, Kathleen E., additional, Owen, Katharine R., additional, Farmer, Andrew J., additional, Frayling, Timothy M., additional, O'Rahilly, Stephen P., additional, Walker, Mark, additional, Levy, Jonathan C., additional, Hodgkiss, Dylan, additional, Hattersley, Andrew T., additional, Kuulasmaa, Teemu, additional, Stančáková, Alena, additional, Barroso, Inês, additional, Bharadwaj, Dwaipayan, additional, Chan, Juliana, additional, Chandak, Giriraj R., additional, Daly, Mark J., additional, Donnelly, Peter J., additional, Ebrahim, Shah B., additional, Elliott, Paul, additional, Fingerlin, Tasha, additional, Froguel, Philippe, additional, Hu, Cheng, additional, Jia, Weiping, additional, Ma, Ronald C.W., additional, McVean, Gilean, additional, Park, Taesung, additional, Prabhakaran, Dorairaj, additional, Sandhu, Manjinder, additional, Scott, James, additional, Sladek, Rob, additional, Tandon, Nikhil, additional, Teo, Yik Ying, additional, Zeggini, Eleftheria, additional, Watanabe, Richard M., additional, Koistinen, Heikki A., additional, Kesaniemi, Y. Antero, additional, Uusitupa, Matti, additional, Spector, Timothy D., additional, Salomaa, Veikko, additional, Rauramaa, Rainer, additional, Palmer, Colin N.A., additional, Prokopenko, Inga, additional, Morris, Andrew D., additional, Bergman, Richard N., additional, Collins, Francis S., additional, Lind, Lars, additional, Ingelsson, Erik, additional, Tuomilehto, Jaakko, additional, Karpe, Fredrik, additional, Groop, Leif, additional, Jørgensen, Torben, additional, Hansen, Torben, additional, Pedersen, Oluf, additional, Kuusisto, Johanna, additional, Abecasis, Gonçalo, additional, Bell, Graeme I., additional, Blangero, John, additional, Cox, Nancy J., additional, Duggirala, Ravindranath, additional, Seielstad, Mark, additional, Wilson, James G., additional, Dupuis, Josee, additional, Ripatti, Samuli, additional, Hanis, Craig L., additional, Florez, Jose C., additional, Mohlke, Karen L., additional, Meigs, James B., additional, Laakso, Markku, additional, Morris, Andrew P., additional, Boehnke, Michael, additional, Altshuler, David, additional, McCarthy, Mark I., additional, Gloyn, Anna L., additional, and Lindgren, Cecilia M., additional

Published
2017
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10. Insulin Resistance Is Accompanied by Increased Fasting Glucagon and Delayed Glucagon Suppression in Individuals With Normal and Impaired Glucose Regulation

Author

Færch, Kristine, primary, Vistisen, Dorte, additional, Pacini, Giovanni, additional, Torekov, Signe S., additional, Johansen, Nanna B., additional, Witte, Daniel R., additional, Jonsson, Anna, additional, Pedersen, Oluf, additional, Hansen, Torben, additional, Lauritzen, Torsten, additional, Jørgensen, Marit E., additional, Ahrén, Bo, additional, and Holst, Jens Juul, additional

Published
2016
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12. 343-OR: Trends in A1C and Lipid Testing, Antilipid Therapy, and Target Attainment following First-Time Glucose-Lowering Drug Treatment in Type 2 Diabetes, Denmark, 2000-2017.

Author

KNUDSEN, JAKOB S., WITTE, DANIEL R., HULMAN, ADAM, RØNN, PERNILLE F., LAURITZEN, TORSTEN, SÔRENSEN, HENRIK T., and THOMSEN, REIMAR W.

Abstract

Objective: To examine 18-year trends in early A1C and lipid control among patients initiating first-time glucose-lowering drug therapy (GLD) for type 2 diabetes. Materials and Methods: Population-based sequential cross-sectional study using healthcare databases covering Northern Denmark (∼1.8 million persons). For all 94,175 GLD initiators during 2000-2017, we examined likelihood of A1C and lipid testing, antilipid therapy, and 1-year glycemic and LDL cholesterol target achievement. Results: The proportion of patients with at least one A1C test increased from 53% in 2000 to 95% in 2017 (Figure, Panel A). Lipid testing increased from 82% to 98% and lipid lowering therapy initiation quintupled from 12% to 61%. Mean pre-treatment A1C declined substantially, from 9.2% (77 mmol/mol) to 7.3% (56 mmol/mol) in 2011, then rose to 7.9% (63 mmol/mol) in 2017 (Panel B). Post-treatment A1C decreased less; pre- and post-treatment LDL cholesterol declined similarly. The proportion of patients achieving glycemic and cholesterol targets increased substantially over time (Panel C). Conclusion: Monitoring and treatment of A1C and cholesterol in early type 2 diabetes have improved considerably over the past 18 years, while quality improvement was somewhat flat after the 2011 change in diagnostic criteria. Disclosure: J.S. Knudsen: None. D.R. Witte: None. A. Hulman: None. P.F. Rønn: Research Support; Self; Amgen AB. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. T. Lauritzen: Advisory Panel; Self; AstraZeneca. Board Member; Self; Novo Nordisk A/S. H.T. Sôrensen: None. R.W. Thomsen: None. Funding: Aarhus University [ABSTRACT FROM AUTHOR]

Published
2019
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13. Progression from IFG and IGT to Diabetes in General Practices Trained in Motivation and Intensive Multifactorial Treatment of Type 2 Diabetes: The ADDITION Study, DK.

Author

Rasmussen, Signe S., Glumer, Charlotte, Lauritzen, Torsten, Sandbaek, Annelli, and Borch-Johnsen, Knut

Subjects
PHYSICIAN training, GENERAL practitioners, DIABETES complications, TYPE 2 diabetes, PEOPLE with diabetes, GLUCOSE tolerance tests, PREDIABETIC state
Abstract

Training general practitioners in intensive pharmacological and non-pharmacological treatment and training in motivational techniques may be effective and feasible in preventing complications in type 2 diabetic patients. This training will change behavior of the general practitioners and may indirectly affect the risk of developing diabetes in individuals with IFG and IGT. In the ADDITION study, a high-risk screening and intervention study for type 2 diabetes, general practitioners are randomized to standard treatment, to intensive multi-factorial treatment or to motivational adherence to/and intensive multifactorial treatment of diabetic patients. From April 2001 to June 2005, 1835 individuals were identified with IFG (n=736) and IGT (n=1099). An OGTT was done after 1 and 3 years. Follow-up data on 1525 individuals are available (standard treatment: n=684, intensive treatment: n=430, motivation + intensive treatment: n=411). Progression rates were calculated per person-years (py). Effect of intervention was analyzed in Poisson regression analyses. In the IFG and IGT group, respectively, 157 and 302 incident cases of diabetes occurred giving progression rates of 12.0 and 17.5 per 100 py. No significant effect of either intervention strategy on the progression was observed. We conclude that in a high-risk screening program incident diabetes at follow-up examinations in individuals with IFG and IGT is a major concern. Training general practitioners in motivational adherence and/or in intensive multifactorial treatment of patients with type 2 diabetes does not affect the progression rates from the prediabetic conditions after 3 years intervention. This could indicate that intervention strategies have to focus on individuals with IFG and IGT directly, at the individual or the general practitioner's level. [ABSTRACT FROM AUTHOR]

Published
2007

14. Constant Subcutaneous Insulin Infusion versus Long-Acting Insulin Injection as Supplement to Oral Anti-Diabetic Drugs in Type 2 Diabetic Patients.

Author

Parkner, Tina, Laursen, Torben, Lauritzen, Torsten, Smedegaard, Jørgen S., and Christiansen, Jens S.

Subjects
INSULIN, ORAL therapy for diabetes, HYPOGLYCEMIC agents, SUBCUTANEOUS injections, TYPE 2 diabetes, PEOPLE with diabetes
Abstract

When using subcutaneous injection of long-acting insulin analogues large variation in the absorption and insulin peak plasma concentrations is a drawback. The aim was to evaluate the potential advantages of constant basal subcutaneous delivery of a short-acting insulin analogue (aspart) versus daily injection of a long-acting insulin analogue (glargine) in type 2 diabetic patients. Twenty-one type 2 diabetic patients with secondary failure to oral antidiabetic drugs were included in this 2-period crossover study. The patients were randomised to an equal additional 24 hours dose of either a short-acting insulin analogue administered as a constant infusion or a once daily bedtime injection of a long-acting insulin analogue for 8 consecutive days. Profiles of serum insulin aspart, serum insulin glargine and plasma glucose were recorded. The intra-subject variability was 41% lower for fasting serum insulin aspart as compared to fasting insulin glargine (p=0.012). The insulin aspart infusion profile appeared to be more flat than the glargine profile. The intra-subject variability for fasting plasma glucose were 28% lower in the insulin aspart infusion period as compared with the insulin glargine injection period, but this failed to reach statistical significance (p=0.104). The plasma glucose profile on the last day in each treatment period was 11% lower for insulin aspart infusion as compared to insulin glargine injection (p=0.002). Hypoglycaemic episodes were few and mild with the majority occurring at daytime in the insulin aspart period. Constant basal subcutaneous delivery of a short-acting insulin analogue provided better insulin and plasma glucose profiles as compared to daily injection of a long-acting insulin analogue without safety concerns in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Published
2007

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