Associate professor

Current project

Genetic prediction of type 2 diabetes and its complications

Type 2 diabetes is a complex polygenic disease where environmental factors interact with genetic factors to cause the disease. While environment has changed dramatically towards more affluent Western life style and less physical activity last decades, our genetics did not change implying that our genes rather determine how we respond to the changes in the environment. Beta-cell capacity to compensate for the increase insulin demands plays a key role in the pathogenesis of the disease. To identify genetic factors which increase risk or protect from developing type 2 diabetes in at high risk individuals will improve disease prediction and help to design more efficient preventive strategies long before disease can occur.

Diabetes epidemic is also an epidemic of devastating chronic diabetic complications. This includes micro-vascular (nephropathy, retinopathy and neuropathy) and macrovascular (coronary heart disease and stroke). However, there exists a sub-population of individuals that despite long duration of diabetes do not develop major diabetic complication, so called "long-term survivors".

To identify genetic and non-genetic factors associated with protection from diabetic complications in patients with long duration of disease we have recently launched a study called PROLONG (PROtective genes in diabetic complications and LONGevity) aiming at ascertainment of 3.000 eligible "long-term survivors" patients with diabetes duration more than 30 years without major diabetic complications in Sweden.

Funding

ALF
Crafoord foundation
Diabetesfonden
European Foundation for the Study of Diabetes
NovoNordisk
Påhlssons
Swedish Heart and Lung Foundation
Swedish Research Council

Highlight articles

1. Lyssenko V, Eliasson L, Kotova O, Pilgaard K, Wierup N, Salehi A, Wendt A, Jonsson A, Marinis YZD, Berglund LM, Taneera J, Balhuizen A, Hansson O, Osmark P, Dunér P, Bröns C, Stancakova A, Kuuisto J, Bugliani M, Saxena R, Ahlqvist E, Kieffer TJ, Tuomi T, Isomaa B, Melander O, Sonestedt E, Orho-Melander M, Nilsson P, Bonetti S, Bonadonna R, Miccoli R, DelPrato S, Marchetti P, Madsbad S, Poulsen P, Vaag A, Laakso M, Gomez MF, Groop L. Pleiotropic effects of a variant in the GIPR gene on islet function and risk of type 2 diabetes. Diabetes, 2011, 9:2424-33.

2. Lyssenko V, Nagorny C, Erdos M, Wierup N, Jonsson A, Spégel P, Bugliani M, Saxena R, Fex M, Pulizzi N, Isomaa B, Tuomi T, Nilsson P, Kuusisto J, Tuomilehto J, Boehnke M, Altshuler D, Sundler F, Eriksson J, Jackson A, Laakso M, Marchetti P, Watanabe R, Mulder H, Groop L. A common variant in the melatonin receptor gene (MTNR1B) is associated with increased risk of future type 2 diabetes and impaired early insulin secretion. Nature Genetics, 2009:82-8.

3. Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, Berglund G, Altshuler D, Nilsson P, Groop L. Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes. The New England Journal of Medicine, 2008: 359, 2220-2232.

4. Diabetes Genetics Initiative of Broad, Lund and Novartis. Genome wide association analysis identifies three novel loci for type 2 diabetes and one for triglycerides levels. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Boström K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Råstam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjögren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S. Science, 316,1331-1336, 2007.

5. Lyssenko V, Lupi R, Marchetti P, Del Guerra S, Orho-Melander M, Almgren P, Sjögren M, Ling C, Eriksson K-F, Lethagen Å-L, Mancarella R, Berglund G, Tuomi T, Nilsson P, Del Prato S, Groop L. Mechanisms by which common variants in the TCF7L2 genes increase risk for future type 2 diabetes. The Journal of Clinical Investigation, 117, 2155-2163, 2007.

6. Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Isomaa B, Forsén B, Nissén M, Homström N, Saloranta C, Taskinen M-R, Groop L , Tuomi T. Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes, 54, 166-174, 2005.