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Published in:

01-10-2013 | Original Article

Prevalence of mitochondrial diabetes in southwestern Finland: a molecular epidemiological study

Authors: Mika H. Martikainen, Tapani Rönnemaa, Kari Majamaa

Published in: Acta Diabetologica | Issue 5/2013

Abstract

Mitochondrial diabetes and deafness (MIDD) is a subtype of diabetes mellitus (DM) that most commonly results from the m.3243A > G mutation in mitochondrial DNA (mtDNA). Sensorineural hearing loss is a typical accompanying feature. Previous studies have suggested a prevalence of ~1–1.5 % for MIDD. We studied the molecular epidemiology of MIDD among young (aged 18–45 years) adults in a defined population in southwestern Finland. Of the identified cohort of 1,532 patients with DM, we received blood samples of 299 patients and analyzed them for the m.3243A > G mutation and for mtDNA haplogroups. We found three DM patients (1.0 %) with the m.3243A > G mutation. All the three patients with DM and m.3243A > G also had severe hearing impairment that required use of hearing aid. MtDNA haplogroup U was more prevalent among patients with maternal family history of DM. We conclude that among young adults, ~1 % of all DM is associated with the m.3243A > G mutation. We suggest that all patients with both DM and hearing impairment, at least in this age group, should undergo investigation for this mutation. Furthermore, our results suggest that mtDNA haplogroup U is associated with maternal family history of DM.

van den Ouweland JMW, Lemkes HHPJ, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PA, van de Kamp JJ, Maassen JA (1992) Mutation in mitochondrial tRNA^Leu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1:368–371PubMedCrossRef

Reardon W, Ross RJM, Sweeney MG, Luxon LM, Pembrey ME, Harding AE, Trembath RC (1992) Diabetes mellitus associated with a pathogenic point mutation in mitochondrial DNA. Lancet 340:1376–1379PubMedCrossRef

Remes AM, Majamaa K, Herva R, Hassinen IE (1993) Adult-onset diabetes mellitus and neurosensory hearing loss in maternal relatives of MELAS patients in a family with the tRNA^Leu(UUR) mutation. Neurology 43:1015–1020PubMedCrossRef

Kadowaki T, Kadowaki H, Mori Y, Tobe K, Sakuta R, Suzuki Y, Tanabe Y, Sakura H, Awata T, Goto Y, Hayakawa T, Matsuoka K, Kawamori R, Kamada T, Horai S, Nonaka I, Hagura R, Akanuma Y, Yazaki Y (1994) A subtype of diabetes mellitus associated with a mutation of mitochondrial DNA. N Engl J Med 330:962–968PubMedCrossRef

van den Ouweland JMW, Lemkes HHPJ, Trembath RC, Ross R, Velho G, Cohen D, Froguel P, Maassen JA (1994) Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA^Leu(UUR) gene. Diabetes 43:746–751PubMedCrossRef

Maassen JA (2002) Mitochondrial diabetes: pathophysiology, clinical presentation, and genetic analysis. Am J Med Genet 115:66–70PubMedCrossRef

Goto Y, Nonaka I, Horai S (1990) A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:651–653PubMedCrossRef

Murphy R, Turnbull DM, Walker M, Hattersley AT (2008) Clinical features, diagnosis and management of maternally inherited diabetes and deafness (MIDD) associated with the 3243A > G mitochondrial point mutation. Diabet Med 25:383–399PubMedCrossRef

Lehto M, Wipemo C, Ivarsson SA, Lindgren C, Lipsanen-Nyman M, Weng J, Wibell L, Widén E, Tuomi T, Groop L (1999) High frequency of mutations in MODY and mitochondrial genes in Scandinavian patients with familial early-onset diabetes. Diabetologia 42:1131–1137PubMedCrossRef

10.

Guillausseau PJ, Massin P, Dubois-LaForgue D, Timsit J, Virally M, Gin H, Bertin E, Blickle JF, Bouhanick B, Cahen J, Caillat-Zucman S, Charpentier G, Chedin P, Derrien C, Ducluzeau PH, Grimaldi A, Guerci B, Kaloustian E, Murat A, Olivier F, Paques M, Paquis-Flucklinger V, Porokhov B, Samuel-Lajeunesse J, Vialettes B (2001) Maternally inherited diabetes and deafness: a multicenter study. Ann Intern Med 134:721–728PubMedCrossRef

11.

Wallace DC, Brown MD, Lott MT (1999) Mitochondrial DNA variation in human evolution and disease. Gene 238:211–230PubMedCrossRef

12.

Chinnery PF, Mowbray C, Patel SK, Elson JL, Sampson M, Hitman GA, McCarthy MI, Hattersley AT, Walker M (2007) Mitochondrial DNA haplogroups and type 2 diabetes: a study of 897 cases and 1010 controls. J Med Genet. doi:10.1136/jmg.2007.048876

13.

Mohlke KL, Jackson AU, Scott LJ, Peck EC, Suh YD, Chines PS, Watanabe RM, Buchanan TA, Conneely KN, Erdos MR, Narisu N, Enloe S, Valle TT, Tuomilehto J, Bergman RN, Boehnke M, Collins FS (2005) Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns. Hum Genet 118:245–254PubMedCrossRef

14.

Hakonen AH, Heiskanen S, Juvonen V, Lappalainen I, Luoma PT, Rantamaki M, Goethem GV, Lofgren A, Hackman P, Paetau A, Kaakkola S, Majamaa K, Varilo T, Udd B, Kaariainen H, Bindoff LA, Suomalainen A (2005) Mitochondrial DNA polymerase W748S mutation: a common cause of autosomal recessive ataxia with ancient European origin. Am J Hum Genet 77:430–441PubMedCrossRef

15.

Majamaa K, Moilanen JS, Uimonen S, Remes AM, Salmela PI, Kärppä M, Majamaa-Voltti KA, Rusanen H, Sorri M, Peuhkurinen KJ, Hassinen IE (1998) Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and stroke like episodes: prevalence of the mutation in an adult population. Am J Hum Genet 63:447–454PubMedCrossRef

16.

Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, Scozzari R, Obinu D, Savontaus ML, Wallace DC (1996) Classification of European mtDNAs from an analysis of three European populations. Genetics 144:1835–1850PubMed

17.

Katagiri H, Asano T, Ishihara H, Inukai K, Anai M, Yamanouchi T, Tsukuda K, Kikuchi M, Kitaoka H, Ohsawa N, Yazaki Y, Oka Y (1994) Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA^Leu(UUR) gene mutation in Japanese patients. Diabetologia 37:504–510PubMedCrossRef

18.

Newkirk JE, Taylor RW, Howell N, Bindoff LA, Chinnery PF, Alberti KG, Turnbull DM, Walker M (1997) Maternally inherited diabetes and deafness: prevalence in a hospital diabetic population. Diabet Med 14:457–460PubMedCrossRef

19.

Tsukuda K, Suzuki Y, Kameoka K, Osawa N, Goto Y, Katagiri H, Asano T, Yazaki Y, Oka Y (1997) Screening of Patients with maternally transmitted diabetes for mitochondrial gene mutations in the tRNA^Leu(UUR) region. Diabet Med 14:1032–1037PubMedCrossRef

20.

Maassen JA, Janssen GMC, t’Hart LM (2005) Molecular mechanisms of mitochondrial diabetes (MIDD). Ann Med 37:213–221PubMedCrossRef

21.

Shanske S, Pancrudo J, Kaufmann P, Engelstad K, Jhung S, Lu J, Naini A, DiMauro S, De Vivo DC (2004) Varying loads of the mitochondrial DNA A3243G mutation in different tissues: implications for diagnosis. Am J Med Genet 130A:134–137PubMedCrossRef

22.

Rahman S, Poulton J, Marchington D, Suomalainen A (2001) Decrease of 3243 A → G mtDNA mutation from blood in MELAS syndrome: a longitudinal study. Am J Hum Genet 68:238–240PubMedCrossRef

23.

Smith ML, Hua XY, Marsden DL, Liu D, Kennaway NG, Ngo KY, Haas RH (1997) Diabetes and mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS): radiolabeled polymerase chain reaction is necessary for accurate detection of low percentages of mutation. J Clin Endocrinol Metab 82:2826–2831PubMedCrossRef

24.

Wong LJ, Lam CW (1997) Alternative, noninvasive tissues for quantitative screening of mutant mitochondrial DNA. Clin Chem 43:1241–1243PubMed

25.

Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14. AppendixPubMedCrossRef

26.

Hirano M, Ricci E, Rowland LP, De Vivo DC, DiMauro S (1991) Clinical definition of MELAS. (Abstract). Ann Neurol 30:299

27.

Takeshima T, Nakashima K (2005) MIDD and MELAS: a clinical spectrum. Intern Med 44:276–277PubMedCrossRef

28.

Suzuki S, Oka Y, Kadowaki T, Kanatsuka A, Kuzuya T, Kobayashi M, Sanke T, Seino Y, Nanjo K, Research Committee for Specific Types of Diabetes Mellitus with Gene Mutations of the Japan Diabetes Society (2003) Clinical features of diabetes mellitus with the mitochondrial DNA 3243 (A–G) mutation in Japanese: maternal inheritance and mitochondria-related complications. Diabetes Res Clin Pract 59:207–217

29.

Guéry B, Choukroun G, Noël LH, Clavel P, Rötig A, Lebon S, Rustin P, Bellané-Chantelot C, Mougenot B, Grünfeld JP, Chauveau D (2003) The Spectrum of systemic involvement in adults presenting with renal lesion and mitochondrial tRNA(Leu) gene mutation. J Am Soc Nephrol 14:2099–2108PubMedCrossRef

30.

Jansen JJ, Maassen JA, van der Woude FJ, Lemmink HA, van den Ouweland JM, t’Hart LM, Smeets HJ, Bruijn JA, Lemkes HH (1997) Mutation in mitochondrial tRNALeu(UUR) gene associated with progressive kidney disease. J Am Soc Nephrol 8:1118–1124PubMed

31.

Nakamura S, Yoshinari M, Doi Y, Yoshizumi H, Katafuchi R, Yokomizo Y, Nishiyama K, Wakisaka M, Fujishima M (1999) Renal complications in patients with diabetes mellitus associated with an A to G mutation of mitochondrial DNA at the 3243 position of leucine tRNA. Diabetes Res Clin Pract 44:183–189PubMedCrossRef

32.

Narbonne H, Paquis-Fluckinger V, Valero R, Heyries L, Pellissier JF, Vialettes B (2004) Gastrointestinal tract symptoms in maternally inherited diabetes and deafness (MIDD). Diabetes Metab 30:61–66PubMedCrossRef

33.

Majamaa K, Finnilä S, Turkka J, Hassinen IE (1998) Mitochondrial DNA haplogroup U as a risk factor for occipital stroke in migraine. Lancet 352:455–456PubMedCrossRef

34.

Martikainen MH, Majamaa K (2010) Epidemiology and characteristics of occipital brain infarcts in young adults in Southwestern Finland. J Neurol 257:259–263PubMedCrossRef

35.

Achilli A, Olivieri A, Pala M, Kashani BH, Carossa V, Perego UA, Gandini F, Santoro A, Battaglia V, Grugni V, Lancioni H, Sirolla C, Bonfigli AR, Cormio A, Boemi M, Testa I, Semino O, Ceriello A, Spazzafumo L, Gadaleta MN, Marra M, Testa R, Franceschi C, Torroni A (2011) Mitochondrial DNA backgrounds might modulate diabetes complications rather than T2DM as a Whole. PLoS One. doi:10.1371/journal.pone.0021029 PubMed

Title: Prevalence of mitochondrial diabetes in southwestern Finland: a molecular epidemiological study
Authors: Mika H. Martikainen
Tapani Rönnemaa
Kari Majamaa
Publication date: 01-10-2013
Publisher: Springer Milan
Published in: Acta Diabetologica / Issue 5/2013
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-012-0393-2

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