Botnia Keskukset

MIKÄ, MISSÄ, MILLOIN?

-	Botnia-tutkimus käynnistettiin vuonna 1990 Pohjanmaalla, jossa viiden terveyskeskuksen(Maalahti, Mustasaari, Närpiö, Pietarsaari, Vaasa) alueelta on kutsuttu tutkimukseen kaikki aikuistyypin (tyypin 2) diabetesta sairastavat henkilöt ja heidän sukulaisensa
-	Vuonna 1994 tutkimus laajennettiin muualle Suomeen ja Etelä-Ruotsiin (ns. SIB-tutkimus).
-	Yhteensä tutkimukseen on saliistunut yli 9000 henkeä 1400:sta perheestä.
-	Viime vuosina on tutkimus laajennettu koskemaan myös nuoruustyypin (tyypin 1) diabetesta sairastavia henkilöitä. Perustutkimuksen yhteydessä pyritään myös selvittämään nk. välimuotodiabetestyyppejä (MODY, LADA, jne) sairastavien osuus ja erityispiirteet.

Sukulaisia, joilla on joko normaali sokerinsietokyky tai alentunut sokerinsietokyky ilman diabetesta, seurataan perustutkimuksen jälkeen seurantatutkimuksessa. Tämän avulla pyritään selvittämään ennusteellisia tekijöitä diabeteksen kehittymiselle. Osalle tehdään tarkempia aineenvaihdunnan selvityksiä ns. clamp-tutkimuksen avulla.

KETKÄ?

Tutkimusta johtaa professori Leif Groop, jonka tie on kulkenut Närpiön terveyskeskuksesta Helsingin Yliopistollisen Keskussairaalan kautta endokrinologian professoriksi Lundin yliopistoon. Vs. tutkimusjohtajana toimii dosentti Tiinamaija Tuomi (HYKS / Malmö)

Leif Groop

Tiinamaija Tuomi

Marju Orho-Melander

Esa Laurila

Molekyylibiologisen laboratorion (Malmö) toiminnasta vastaavat FT Marju Orho-Melander ja laboratorioinsinööri Esa Laurila.

 
Taloudesta vastaa LT Carola Saloranta (HYKS).Paikallisena koordinaattorina on alkuvuosina toiminut Vaasan keskussairaalan sisätautiyli-lääkäri Michael Nissen ja vuodesta 1999 Pietarsaaren sairaalan sisätautiylilääkäri Bo Isomaa.

Carola Saloranta

Bo Isomaa

Michael Nissen

Rasva-aineenvaihdunnan häiriöiden tutkimuksesta vastaa professori Marja-Riitta Taskinen HYKS:istä.

Marja-Riitta Taskinen

Kukin keskuksista toimii itsenäisesti lääkärin, diabeteshoitajan ja laboratoriohoitajan muodostamana työryhmänä.

BOTNIAKESKUKSET

HELSINKI

LUNDIN YLIOPISTO

NÄRPIÖ

MUSTASAARI

MAALAHTI

PIETARSAARI

VAASA

BIOINFORMATIIKKA

MUUT YHTEISTYÖKUMPPANIT

RAHOITUS

Botnia-tutkimusta rahoittavat Suomessa pääasiassa Sigrid Juséliuksen Säätiö, Suomen Akatemia, Diabetestutkimussäätiö ja Helsingin yliopistollinen keskussairaala (EVO). Saamme myös jatkuvaa tukea Finska Läkaresällskapetilta, Ollqvistin Säätiöltä, Närpiön sairaanhoitosäätiöltä sekä Närpiön, Maalahti-Korsnäsin, Mustasaaren, Pietarsaaren ja Vaasan terveysasemilta. Vuodesta 2001 lähtien kuulumme myös Folkhälsanin Tutkimuskeskukseen.

Ruotsin Botniatoimintaa rahoittavat Medicinska forskningsrådet (MFR-K99-31X-10858-06A), EU (QLG-CT-1999-00546-GIFT), JDF Wallenberg, Direktör Albert Påhlssons Stiftelse, Universitetssjukhuset MAS forskningsfonder, Novo Nordisk Fonden, Crafoord Stiftelsen, Inga Britt och Arne Lundbergs Forkningsstiftelse.

VÄITÖSKIRJAT 

Marju Orho-Melander	Human glycogen synthases (April 1999)
Carol Forsblom	Microalbuminuria in diabetic and non-diabetic subjects: association with diabetic nephropathy, cardiovascular disease and insulin resistance (Maj 1999)
Markku Lehto	Search for genes increasing susceptibility to MODY and type 2 diabetes (Sept 1999)
Olle Melander	Genetic factors in primary hypertension. With emphasis on renal sodium reabsorption (April 2000)
Martin Carlsson	Common variants in genes regulating free fatty acid metabolism and risk of type 2 diabetes and cardiovascular disease (Maj 2001)
Mia Klannemark	Genetics of type 2 diabetes and the metabolic syndrome (Sept 2001)
Bo Isomaa	Chronic diabetic complications in clinically, immunologically and genetically defined subgroups (Sept 2001)
Cecilia M. Lindgren	Search for type 2 diabetes susceptibility genes using multiple approaches (Feb 2002)
Xudong Huang	Identification of abnormally expressed genes in skeletal muscle contributing to insulin resistance and type 2 diabetes (March 2002)
ÅsaLinda Lethagen	Clinical, Genetic and Metabolic Characterisation of LADA - Latent Autoimmune Diabetes in Adults (April 2002)
Kristina Bengtsson	Genetic Factors Contributing to Hypertension With Emphasis on Hypertension in Type 2 Diabetes (April 2002)
Haiyan Li	Genetic interaction betwen type 1 and type 2 diabetes (September 2002)

Devjit Tripathy

Pathogenesis of type 2 diabetes - role of defects in insulin secretion and insulin sensitivity (May 2003)

TULEVIA VÄITÖKSIÄ

JULKAISUT  

1	Eriksson J, Häggblom M, Forsén B, Groop L: Clinical and metabolic characteristics of patients with Type 1 and Type 2 diabetes. Diabetic Medicine 1992;9:654-660.
2	Forsblom CM, Eriksson JG, Ekstrand A-M, Taskinen M-R, Groop L: Insulin resistance and abnormal albumin excretion in non- diabetic first degree-relatives of patients with Type 2 diabetes. Diabetologia 38;363-369, 1995.
3	Birkeland K, Torjesen PA, Eriksson J, Valler S, Groop L: Hyperproinsulinemia of type 2 diabetes is not present prior to the development of hyperglycemia. Diabetes Care 17:1307- 1310,1994.
4	Lehto M, Huang X, Davis, EM, Le Beau M, Bell G, Groop L: Human hexokinase II gene: exon-intron organization, mutation screening in Type 2 diabetes mellitus, and identification of a pseudogene on chromosome 4. Diabetologia 38:1466-1474,1995.
5	Knudsen P, Eriksson J, Kahri J, Lahdenperä S, Groop L, , Taskinen M-R and the Botnia Study Group:Changes of lipolytic enzymes cluster with insulin resistance syndrome. Diabetologia 38:344-350, 1995
6	Widén E, Lehto M, Kanninen T, Walston J, Shuldiner A, Groop L: Association between a polymorphism of the beta-3-adrenergic receptor gene and insulin resitance in Finnish nondiabetic subjects. New Engl J Med 333: 348-351,1995.
7	Groop L, Forsblom C, Lehtovirta M, Tuomi T, Karanko S, Nissén M, Ehrnström B-O, Forsén B, Isomaa B, Snickars B, Taskinen M-R: Metabolic consequences of a family history of NIDDM: The Botnia Study. Evidence for sex-specific parental effects. Diabetes 45;1585-1593, 1996.
8	Huang X, Orho M, Lehto M, Groop L: Lack of association between the glucagon receptor gene and NIDDM in Finland. Diabetologia 38:1246-1248, 1995.
9	Orho M, Carlsson M, Kanninen T, Groop LC: Polymorphism at the rad gene is not associated with NIDDM in Finns. Diabetes 45:429-433, 1996.
10	Tilly-Kiesi M, Knudsen P, Groop L, Taskinen M-R and the Botnia Study Group: Hyperinsulinemia is associated with abnormalities of lipoprotein subclasses in glucose-tolerant relatives of NIDDM patients. J Lipid Res 37:1569-1578, 1996.
11	Mahtani M, Widén E, Lehto M, Thomas J, McCarthy M, , Brayer J, Bryant B, Chan G, Daly M, Forsblom C, Kanninen T, Kirby A, Kruglyak L, Munnelly K, Parkkonen M, Reeve-Daly M, Weawer A, Brettin T, Duyk G, Lander E, Groop L: Mapping of a gene for NIDDM associated with an insulin secretion defect by a genome scan in Finnish famlies. Nature Genetics 14; 90-94, 1996.
12	Kellerer M, Rett K, Renn W, Groop L, Häring H:Circulating TNF-a and leptin levels in offspring of NIDDM patients do not correlate to individual insulin sensitivity. Horm Metab Res 28;737-744,1996.
13	Lehto M, Tuomi T, Mahtani M, Widén E, Forsblom C, Gullström M, Sarelin L, Isomaa B, Kanninen T, Lehtovirta M, Hyrkkö A, Orho M, Kirby A, Brettin T, Thomas J, Duyk G, Lander ES, Taskinen M-R & Groop L:: Early-onset diabetes linked to chromosome 12 (MODY3) is characterized by a severe insulin secretion defect. J Clin Invest, 99;582-591,1997.
14	Glucksmann SA, Lehto M, Tayber O, Scotti S, Berkemeier L, Pulido JC, Wu Y, Nir W-J, Fang L, Markel P, Munnelly KD, Goranson G, Orho M, Young BM, Whitacre JL, Menimen Cmc, Wantman M, Tuomi T, Warram J, Forsblom CM, Carlsson M, Rosenzweig J, Kennedy G, Duyk GM, Krolewski AS, Groop LC, Thomas JD: Novel mutations and a mutational hotspot in the MODY3 gene. Diabetes 46;1081-1086,1997.
15	Isomaa Bo, Henricsson M, Lehto M, Forsblom C, Karanko S, Sarelin M, Häggblom M, Groop L: Chronic complications in patients with MODY3 diabetes.Diabetologia 41:467-473, 1998.
16	Klannemark M, Orho M, Langin D, Laurell H, Holm C, Reynisdottir S, Arner P, Groop L: The putative role of the hormone sensitive lipase gene in the pathogenesis metabolic syndrome. Diabetologia 41;1515-22,1998.
17	Tuomi T, Carlsson Å-L, Li H, Cano L, Isomaa B, Miettinen A, Nilsson A, Nissén M, Ehrnström B-O, Forsén B, Snickars B, Lahti K, Forsblom C, Saloranta C, Taskinen M-R and Groop L: Clinical and genetic characteristics of type 2 diabetes with and without GAD antibodies. Diabetes 48;150-57, 1999.
18	Orho-Melander M, Shimomura H, Sanke T, Nanjo Kisho, Hansen T, Pedersen O, Groop LC:Expression of mutations in the muscle glycogen synthase gene (GYS1) and studies of their biological consequences in Scandinavian populations. Diabetes 48;918- 920, 1999.
19	Klannemark M, Orho M, Groop L: : No relationship between variants in the uncoupling protein 2 gene and energy expenditure. Eur J Endocrinology 139;217-223, 1998.
20	Orho M, Almgren P, Kanninen T, Forsblom C, Groop LC: : A paired sibling analysis of the XbaI polymorphism in the muscle glycogen synthase gene. Diabetologia 42;1138-45,1999.
21	Lehto M, Wipemo C, Ivarsson S, Lindgren C, Lipsanen-Nyman M, Tuomi T, Weng J, Wibell L, Widén E, Groop L: High frequency of MODY and mitochondrial gene sequence variations in Scandinavian families with early-onset diabetes. Diabetologia 42;1131-37,1999.
22	Forsblom CM, Kanninen T, Lehtovirta T, Kaprio J, Saloranta C, Groop L: Albumin excretion is an inherited trait in families with NIDDM? Diabetologia 42;1359-1366,1999.
23	Isomaa B, Henricsson M, Tuomi T, Sarelin L, Almgren P, Taskinen M-R, Groop L: Chronic complications in patients with slowly progressing type 1 diabetes (LADA ). Diabetes Care 22;1347-53,1999.
24	Weng JP, Lehto M, Forsblom C, Huang X, Li H, Groop LC: Screening for mutations in the HNF-1b gene in Scandinavian families with early-onset diabetes and/or kidney disease. Diabetologia 43;131.134, 2000.
25	Tripathy D, Carlsson M, Almgren P, Isomaa B, Nissén M, Lahti K, Lehtovirta M, Forsén B, Snickars B, Taskinen M-R, Tuomi T, Groop LC: Insulin secretion and insulin sensitivity in relation to glucose tolerance (The Botnia Study) . Diabetes 49; 2000.
26	Carlsson ÅL, Isomaa B, Sundqvist G, Forsén B, Lahti K, Groop L, Tuomi T: Insulin and glucagon secretion and insulin sensitivity in patients with slowly progressing autoimmune diabetes (LADA). J Clin Endocrinol Metab 85;76-80, 2000.
27	Gu HG, Almgren P, Lindholm E, Frititta L, Pizzuti A, Trischitta V, Groop L: Association of a naturally occurring variant c.534A>C(Q121K) in the glycoprotein PC-1 gene with features of the metabolic syndrome. Diabetes 49; 1601-1603, 2000.
28	Melander O, Bengtsson K, Orho M, Lindblad U, Groop L, Hulthén L: The role of the a-adducin gene in primary hypertension and microalbuminuria. J Human Hypertension 14;343-46,2000.
29	Lindgren C, Mahtani M, Widén E, McCarthy M, Kirby A, Daly M, Lehto M, Thomas J, Glucksman S, Brayer J, Kanninen T, Almgren P, Tuomi T, Groop LC& Lander ES:A genome-wide search for susceptibility loci linked to type 2 diabetes in Finnish families (the Botnia Study). J Hum Mol Genetics 70,509-516, 2002. (Botnia 1)
30	Li H, Isomaa B, Almgren P, Groop L, Tuomi T: Consequences of a family history of type 1 or type 2 diabetes on the phenotype of type 2 diabetes. Diabetes Care 23;589-594, 2000.
31	Isomaa B, Almgren P, Tuomi T, Forsblom C, Forsén B, Lahti K, Snickars B, Nissén M, Taskinen M-R, Groop L: Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 24; 683-689, 2001.
32	Klannemark M, Suurinkeroinen L, Orho-Melander M, Groop L, Taskinen M-R: The Asn291Ser polymorphism of the lipoprotein lipase gene is associated with dyslipidemia in healthy subjects but not in type 2 diabetic patients. Diabetic Medicine 17;599-605, 2000.
33	Lehtovirta M; Forsén B, Gullström M, Häggblom M, Eriksson JG, Taskinen M-R, Groop L: Metabolic effects of metformin in patients with impaired glucose tolerance. Diabetic Medicine 18:578-583, 2001.
34	Tripathy D, Carlsson M, Almgren P, Isomaa B, Taskinen M-R, Tuomi T, Groop LC: Insulin Secretion and Insulin Sensitivity in Relation to Glucose Tolerance. Lessons from the Botnia Study. Diabetes 49: 975-980, 2000.
35	Melander O, Orho-Melander M, Bengtsson K, Lindblad U, Råstam L, Groop L: Genetic variants of the thiazide sensitive NaCl-cotransporter in Gitelman's syndrome and primary hypertension. Hypertension 36;389-394, 2000.
36	Melander O, Orho-Melander M, Bengtsson K, Lindblad U, Råstam L, Groop L, Hulthén L: Association between variants in the 11b-hydroxysteroid dehydrogenase type 2 gene and primary hypertension. J Hum Hypertension 14;819-823,2001.
37	Tripathy D, Carlsson Å-L, Lehto M, Isomaa B, Tuomi T, Groop L:: Insulin secretion and insulin sensitivity in diabetic subgroups: studies in the prediabetic and diabetic state. Diabetologia 43;1476-1483, 2001.
38	Horikawa Y, Oda N, Cox NJ,Li X, Orho-Melander M, Hara M, Hinokio Y, Lindner TH, Mashima H, Schwarz PEH, del Bosque-Plata L, Horikawa Y, Oda Y, Yoshiuchi I, Colilla S, Polonsky KS, Wi S, Concannon P, Iwaskai N, Schulze J, Baier LJ, Bogardus C, Groop L, Boerwinkle E, Hanis, CL, Bell, GI: Genetic variation in the calpain 10 gene (CAPN10) is associated with type 2 diabetes mellitus. Nature Genetics 26;1-13, 2000.
39	Altshuler D, Hirschhorn JN, Klannemark M, Lindgren C, Daly M, Vohl M-C, Nemesh J, Lane C, Schaffner SF, Bolk S, Brewer C, Tuomi T, Gaudet D, Hudson TJ, Groop L, Lander ES: The common PPARg Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes. Nature Genetics 26;76-80, 2000.
40	Li H, Lindholm E, Almgren P, Gustafsson Å, Forsblom C, Groop L, Tuomi T: Possible HLA-defined genetic interaction between type 1 and type 2 diabetes. J Clin Endocrinol Metab 86;574-582,2001.
41	Weng J, MacFarlane W, Lehto M, Gu HF, Ivarsson SA, Wibell L, Smith T, Groop LC: Functional consequences of mutations in the MODY4 (IPF-1) gene and ocurrence in families with MODY3. Diabetologia 44;249-258, 2001.
42	Parker A, Meyer J, Lewitzky S, Rennich JS, Chan G, Thomas JD, Almgren P, Lehtovirta M, Forsblom C, Hyrkkö A, Carlsson M, Lindgren C, Groop LC: A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p.11.31. Diabetes, 2001; 50: 675-680. (Botnia 2)
43	Bengtsson K, Orho-Melander K, Melander O, Lindblad U, Ranstam J, Råstam L, Groop L:The Arg16Gly polymorphism in the b2-adrenergic receptor gene is associated with hypertension in subjects with type 2 diabetes. Hypertension 37; 1303-1308,2001.
44	Bengtsson K, Melander O, Orho-Melander M, Lindblad U, Ranstam J, Råstam L, Groop L: Polymorphism in the b1 adrenergic receptor gene and hypertension. Circulation, Circulation 104: 187-190, 2001.
45	Lindgren C, Widén E, Tuomi T, Li H, Melander O, Lehto M, Weng J, Almgren P, Groop L: Contribution of known and unknown susceptibility genes to early-onset diabetes in Scandinavia - evidence for heterogeneity. Diabetes, 51:1009-1017, 2002. (Botnia 3)
46	Isomaa B, Henriksson M, Almgren P, Tuomi T, Taskinen M-R, Groop L: The metabolic syndrome influences the risk of chronic complications in patients with Type II Diabetes. Diabetologia 44:1148-1154, 2001.
47	Lindgren C, Nilssson A, Orho-Melander M, Almgren P, Groop L: Characterization of the annexin I gene and evaluation of its role in type 2 diabetes. Diabetes 50:2402-2405, 2001.
48	Hirschorn JN, Lindgren C, Daly MJ, Kirby A, Schaffner S, Altshuler D, Burtt NP, Gaudet D, Groop L, Lander E:Multiple genome wide analyses of stature, a model of complex genetic trait, reveal several regions with evidence of linkage to adult height. Am J Hum Genet 69:106-116, 2001.
49	J Weng, M Ekelund, M Lehto, H Li, G Ekberg, A Frid, A Åberg, L Groop, K Berntorp: Screening for MODY Mutations, GAD Antibodies, and Type 1 Diabetes-Associated HLA Genotypes in Women With Gestational Diabetes Mellitus. Diabetes Care 25;68-71, 2002.
50	Lindgren C M, Mahtani M M, Widén E, McCarthy M I, Daly M J, Kirby A, Reeve M P, Kruglyak L, Parker A, Meyer J, Lehto M, Almgren P, Kanninen T, Tuomi T, Groop LC & Lander E S: Genomewide search for Type 2 Diabetes Mellitus Susceptibility Loci in Finnish Families: The Botnia Study. Am J Hum Genetics 70: 509-516, 2002.
51	Lethagen ÅL, Ericsson U-B, Hallengren B, Groop LC, Tuomi T: Glutamic Acid Decarboxylase Antibody Positivity Is Associated with an Impaired Response to Glucose and Arginine in Nondiabetic patients with Autoimmune Thyroiditid. J Clin Endocrinol Metab, 87(3):1177-1183, 2002.
52	A. Stride, M. Vaxillaire, T. Tuomi, F. Barbetti, P. R. Njølstad, T. Hansen, A. Costa, I. Conget, O. Pedersen, O. Søvik, R. Lorini, L. Groop, P Froguel and A.T. Hattersley for The GIFT MODY Consortium: The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia, 45:427-435, 2002.
53	Orho-Melander M, Klannemark M, Svensson MK, Ridderstråle M, Lindgren CM and Groop L: Variants in the Calpain-10 Gene Predispose to Insulin Resistance and Elevated Free Fatty Acid Levels. Diabetes 51: 2658-2664, 2002.
54	A. Stride, M. Vaxillaire, T. Tuomi, F. Barbetti, P. R. Njølstad, T. Hansen, A. Costa, I. Conget, O. Pedersen, O. Søvik, R. Lorini, L. Groop, P. Froguel and A.T. Hattersley for The GIFT MODY Consortium: The genetic abnormality in the beta cell determines the response to an oral glucose load. Diabetologia, 45:427-435, 2002.
55	Engert JC, Vohl M-C, Williams SM, Lepage P, Loredo-Osti JC, Faith J, Doré C, Renaud J, Burtt NP, Villeneuve A, Hirschhorn JN, Altshuler D, Groop LC, Despres J-P, Gaudet D, Hudson TJ: 5'flanking variants of resistin are associated with obesity. Diabetes 51;1629-34, 2002.
56	McCarthy JJ, Lewitzky S, Reeves C, Permutt A, Glaser B, Groop L, Lehner T and Meyer JM: Polymorphisms of the HDL Receptor Gene Associated with HDL Cholesterol Levels in Diabetic Kindred from Three Populations. Hum Hered 55:163-170, 2003.
57	Tripathy D, Carlsson M, Almgren P, Isomaa B, Taskinen M-R, Tuomi T, Groop LC: Insulin Secretion and Insulin Sensitivity in Relation to Glucose Tolerance. Lessons from the Botnia Study. Diabetes 49: 975-980, 2000.
58	Tripathy D, Almgren P, Tuomi T, Groop L: Comparison of measures of insulin sensitivity and insulin secretion in subjects with varying degree of glucose tolerance. Submitted.
59	Ylönen K, Alfthan G, Groop L, Saloranta C, Aro A, Virtanen SM and the Botnia Research Group: Dietary intakes and plasma concentrations of carotenoids and tocopheroles in relation to glucose metabolism in subjectsat high risk of type 2 diabetes: the Botnia Dietary Study1-3. Am J Clin Nutr 77:1434-41, 2003.
60	Tripathy D, Wessman Y, Gullström M, Tuomi T, Groop L: Importance of Obtaining Independent Measures of Insulin Secretion and Insulin Sensitivity During the Same Test: Results with the Botnia clamp. Diabetes Care 26: 1395-1401.
61	Suviolahti E, Oksanen LJ, Öhman M, Cantor RM, Ridderstråle M, Tuomi T, Kaprio J, Rissanen A, Mustajoki P, Jousilahti P, Vartiainen E, Silander K, Kilpikari R, Salomaa V, Groop L, Kontula K, Peltonen L, and Pajukanta P: The SLC6A14 gene shows evidence of association with obesity, J Clin Invest 112:1762-1772, 2003.
62	Mitchell SMS, Vaxillaire M, Thomas H, Parrizas M, Benmezroua Y, Costa A, Hansen T, Owen K, Tuomi T, Pirie F, Ryffel GU, Ferrer J, Froguel P, Hattersley AT, Frayling TM: Rare variants identified in the HNF- 4alpha beta-cell-specific promoter and alternative exon 1 lack biological significance in maturity onset diabetes of the young and young onset. Diabetologia 45:1344-1348, 2002.
63	Cervin C, Orho-Melander M, Ridderstråle M, Lehto M, Barg S, Groop L and Cilio CM: Characterization of a naturally occurring mutation (L107I) in the HNF1 alpha (MODY3) gene. Diabetologia 45;1703-1708, 2002.
64	Li H, Groop L, Nilsson A, Weng J, and Tuomi T: A Combination of Human Leukocyte Antigen DQB1*02 and the Tumor Necrosis Factor a Promoter G308A Polymorphism Predisposes to an Insulin-Deficient Phenotype in Patients with Type 2 Diabetes. J Clin Endocrinol Metab, 88: 2767-2774, 2002.
65	Ridderstråle M; Klannemark M, Carlsson E, Kösters C, Enerbäck S, Tornqvist H, Storgaard H, Vaag A, Groop L: FOXC2 is a candidate gene for insulin resistance in human obesity and type 2 diabetes mellitus. Diabetes 51:3554-3560, 2002.
66	Antonelli A, Tuomi T, Nannipieri M, Fallahi P, Nesti C, Okamoto H, Groop L, Ferrannini E: Autoimmunity to CD38 and GAD in type 2 and type 1 diabetes: CD38 and HLA genotypes and clinical phenotypes. Diabetologia 45: 1298-1306, 2002.
67	Tuomi T, Li H, Nilsson A, Altshuler D, Hirschhorn J, Groop L: The insulin gene VNTR affects body mass and insulin concentrations in patients with type 2 diabetes. Diabetes, prel. acceptance.
68	Saloranta C, Hershon K, Ball M, Dickinson S and Holmes D: Efficacy and Safety of Nateglinide in Type 2 Diabetic Patients with Modest Fasting Hyperglycemia. J Clin Endocrinol Metab, 87(9):4171-4176, 2002.
69	Saloranta C, Guitard C, Pecher E, Pablos-Velasco P de, Lahti K, Brunel P, Groop L: Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population. Diabetes Care 25(12): 2141-2146, 2002
70	Frayling TM, Lindgren CM, Chevre JC, Menzel S, Wishart M, Benmezroua Y, Brown A, Evans JC, Subba Rao PV, Dina C, Kanninen T, Bulman MP, Wang Y, Mills J, Mahtani M,M, Costa A, Cognet I, Hansen T, Pedersen O, Ellard S, Tuomi T, Groop L, Froguel P, Hattersley AT, Vaxillaire M: Meta-analysis of genome wide scans in families with maturity onset diabetes of the young (MODY): evidence for further genetic heterogeneity. Diabetes, prel. acceptance.
71	Tripathy D, Lindholm E, Isomaa B, Saloranta C, Almgren P, Tuomi T, Groop L: Familiality of metabolic abnormalities is dependent on age at onset and phenotype of the type 2 diabetic proband, Am J Physiol Endocrinol Metab 285:E1297-E1303, 2003.
72	Demenais F, Kanninen T, Lindgren CM, Withshire S, Gaget S, Dandrieux C, Almgren P, Sjögren M, Hattersley A, Dina C, Tuomi T, McCarthy MI, Vaxillaire M, Froguel P and Groop L: A meta-analysis of four European genome screens (GIFT Consortium) shows evidence for a novel region on chromosome 17p11.2-q22 linked to type 2 diabetes. Human Molecular Genetics 12:1865-173, 2003.
73	Ylönen K, Saloranta C, Kronberg-Kippilä C, Groop L, Aro A, Virtanen SM, the Botnia Research Group: Association of Dietary Fiber With Glucose metabolism in Nondiabetic Relatives of Subjects With Type 2 Diabetes. Diabetes Care 26:1979-1985, 2003.
74	Cervin C, Liljeström B, Heikkinen S, Tuomi T, Groop L, Cilio C: Challenging monogenic diabetes. Functional consequences of cosegregation of MODY 3 and MIDD. Diabetes 53;1894-99, 2004.
75	Florez JC, Burtt N, de Bakker PIW, Almgren P, Tuomi T, Holmkvist J, Gaudet D,. Hudson TJ, Schaffner SS, Daly MJ, Hirschhorn JN, Groop L and Altshuler D: Haplotype structure and genotype-phenotype correlations of the sulfonyulrea receptor (SUR1) and the islet ATP-sensitivie potassium channel (Kir 6.2) gene region. Diabetes 53:1360-1368,2004.
76	Snapir A, Scheinin M, Groop LC, Orho-Melander M: The insertion/deletion variation in the alpha2B-adrenoceptor does not seem to modify the risk for acute myocardial infarction, but may modify the risk for hypertension in sib-pairs from families with type 2 diabetesCardiovascular Diabetology 2003, 2:15 (24 november 2003) (http://www.cardiab.com/content/pdf/1475-2840-2-15.pdf)
77	Tripathy D, Almgren P, Tuomi T, Groop L: Contribution of insulin-stimulated glucose uptake and basal hepatic glucose production to surrogate measures of insulin sensitivity. Diabetes Care 27;2204-2210,2004.
78	Tripathy D, Eriksson K-F, Orho-Melander M, Fredriksson J, Ahlqvist G, Groop L: Parallel manifestation of insulin resistance and b -cell decompensation are compatible with a common defect in type 2 diabetes. Diabetologia 47:782-93,2004.
79	Magnusson M, Melander O, Israelsson B, Grubb A, Groop L, Jovinge S: Elevated plasma levels of Nt-proBNP in paitents with type 2 diabetes without known cardiovascular disease. Diabetes Care,27;1929-35,2004.
80	Ellmark-Bengtsson S, Nilsson J, Orho-Melander M, Dahlberg K, Groop L, Bjursell G: Correlation between polymorphism in the carboxyl ester lipase gene and serum cholesterol profile. Eur J Hum Genet., in press.
81	Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Nissén, M, Isomaa B, Forsen B, Holmström N, Saloranta C, Taskinen M-R, Groop L and Tuomi T for the Botnia Study Group: Predictors and Longitudinal Changes in Insulin Sensitivity and Secretion Preceding Onset of Type 2 Diabetes. Diabetes 54:166-174, 2005.
82	Liljestrom B, Akthan-Collan K, Isomaa B, Sarelin L, Uutela A, Groop L, Kaariainen H, Tuomi T: Genetic testing for MODY: uptake, attitude and com parison with hereditary non-polyposis colorectal cancer. Daibetologia, prel.acceptance
83	Jose C. Florez, Marketa Sjögren, Noël Burtt, Marju Orho-Melander, Steve Schaye, Maria Sun, Peter Almgren, Tiinamaija Tuomi, Daniel Gaudet, Thomas J. Hudson, Mark J. Daly, Kristin G. Ardlie, Joel N. Hirschhorn, David Altshuler and Leif Groop: Association testing in 9000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes. Diabetes 53;3313-3318,2004.
84	Lyssenko V, Anevski D, Almgren P, Sjogren M, Svensson M, Orho-Melander M, Tuomi T, Groop L for the Botnia Research Group: Genetic prediction of type 2 diabetes. Submitted (PloS Medicine)