|
BOTNIA STUDY
Info@Botnia-study.fi
|
|
|
Approximately 150 000 persons in Finland and about 1,25 million persons in the world have diabetes. The number is constantly growing. Both environmental and hereditary factors influence the growth.
|
The aim of the study is to:
|
-
|
identify hereditary factors (genes) that cause diabetes
|
-
|
identify environmental factors that cause diabetes
|
-
|
identify early metabolic disturbance in subjects at risk of developing diabetes (relatives of diabetic subjects)
|
-
|
identify factors that influence the risk of developing diabetes and with the help of the above
|
-
|
develop ways to prevent diabetes and its complications.
|
 Botnia Center
WHAT, WHERE, WHEN?
-
|
The Botnia Study was begun in 1990 in Pohjanmaa, Finland. From five public health care districts (Malax, Korsholm, Närpes, Jakobstad, Vasa) all the people suffering from adult-onset (type 2) diabetes and their families were invited to participate in the study.
|
-
|
In 1994 the study was expanded to the rest of Finland and to the south of Sweden (so called SIB-study).
|
-
|
Altogether more than 9000 persons from 1400 families have participated in the study. |
-
|
During the last few years the study has expanded to people with young-onset (type 1) diabetes. At the Basic screening we also aim at discovering the heterogeneity of diabetes and the contribution of so-called mixed types of diabetes (MODY, LADA, etc) and their special features.
|
Nondiabetic relatives with either normal glucose tolerance or impaired glucose tolerance, are invited to the follow-up study to find factors predisposing to diabetes. For some of these subjects, we perform thorough metabolic investigations, e.g. an euglycemic clamp-study.
WHO?
The study is led by professor Leif Groop, who has progressed from the public health care center in Närpiö, via the University hospital in Helsinki, to being the Professor of endocrinology at the University of Lund.
Assistant principal Investigator,Ass. professor Tiinamaija Tuomi (Helsinki University Central Hospital & University of Lund )
|

Leif Groop
|
 Tiinamaija Tuomi
|
 Marju Orho-Melander
|
 Esa Laurila
|
PhD Marju Orho-Melander and laboratory engineer Esa Laurila are in charge of the Molecular Biology laboratory (Malmö)
MD, PhD Carola Saloranta takes care of the Economy (Helsinki University Central Hospital). The head of the Department of Medicine at the Central Hospital of Vaasa, Michael Nissen served as the local coordinator during the first years of the study. Since 1999 the head of the department of medicine at the Malm hospital in Pietarsaari Bo Isomaa has been the local coordinator.
 Carola Saloranta
|
 Bo Isomaa
|
 Michael Nissen
|
|
Professor Marja-Riitta Taskinen from the Helsinki University Central Hospital is in charge of the lipid research.
|
 Marja-Riitta Taskinen
|
|
All the centers work independently, in teams consisting of a physician, a diabetes nurse and a laboratory nurse.
BOTNIA CENTERS
FINANCING
The Botnia Study in Finland is mainly financed by Sigrid Jusélius Foundation, The Academy of Finland, Diabetes Research Foundation and Helsinki University Central Hospital (EVO). We have also received continuous support from Finska Läkaresällskapet, Ollqvist Foundation, Närpes Sjukvårdsfond and the health centers in Närpes, Malax-Korsnäs, Korsholm, Jakobstad och Vasa. Since the second quartile of 2001 we are also a part of the Folkhälsan Research Center.
The Botnia research in Sweden in financed by Swedish mMdical Research Foundation (MFR-K99-31X-10858-06A), European Union (QLG-CT-1999-00546-GIFT), JDF Wallenberg, Albert Påhlsson Foundation, Malmö University Hospital Research Funds, the Novo Nordisk Foundation, Crafoord Foundation, Inga Britt och Arne Lundbergs ForkningsFoundation.
PhD THESIS
|
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)
|
UPCOMING DISSERTATIONS
PUBLICATIONS
|
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) |
|
|
|