Skip to main content
Erschienen in: Diabetologia 9/2009

01.09.2009 | Article

Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications

verfasst von: J. Wong, S. V. McLennan, L. Molyneaux, D. Min, S. M. Twigg, D. K. Yue

Erschienen in: Diabetologia | Ausgabe 9/2009

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

We examined whether age of type 2 diabetes onset is related to mitochondrial DNA content in peripheral blood monocytes (PBMCs).

Methods

PBMCs were isolated from 65 patients with type 2 diabetes. To minimise age as a confounder, only patients aged ≥50 years were studied. Sample mitochondrial DNA (mtDNA) content was determined by amplification of the mitochondrial gene CYT-B (also known as MT-CYB) and adjusted for single-copy nuclear control genes (36B4 [also known as RPLPO] and GAPDH).

Results

Age of diabetes onset ranged from 25 to 69 years. There was a significant positive relationship between age of diabetes onset in quartiles and mtDNA content for the whole group (p = 0.02 for trend). When stratified by the presence of diabetes complications, a strong positive relationship was observed between age of diagnosis and mtDNA content for participants without diabetic complications (r = 0.7; p = 0.0002), but not for those with complications (r = −0.04; p = 0.8). Multivariate analysis confirmed age of onset and complication status as independent determinants. There was co-linearity between age of onset and disease duration, with similar relationships also seen between duration and mtDNA content.

Conclusions/interpretation

An earlier age of type 2 diabetes onset is associated with a lower PBMC mtDNA content, but only in patients without diabetes complications. This may reflect a differing biology of PBMC mtDNA in those with early-onset diabetes and those who are prone to complications. PBMC mtDNA depletion may accelerate diabetes onset; however the independent effect of diabetes duration remains to be evaluated.
Literatur
1.
Zurück zum Zitat Yoshiharu T, Toshiharu I, Kana M, Toru E, Azuma K (2008) Predictors of glycemic control in Japanese subjects with type 2 diabetes mellitus. Metab Clin Exp 57:453–457 Yoshiharu T, Toshiharu I, Kana M, Toru E, Azuma K (2008) Predictors of glycemic control in Japanese subjects with type 2 diabetes mellitus. Metab Clin Exp 57:453–457
2.
Zurück zum Zitat Hillier TA, Pedula KL (2003) Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care 26:2999–3005PubMedCrossRef Hillier TA, Pedula KL (2003) Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care 26:2999–3005PubMedCrossRef
3.
Zurück zum Zitat Wong J, Molyneaux L, Constantino M, Twigg SM, Yue DK (2008) Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors. Diabetes Care 31:1985–1990PubMedCrossRef Wong J, Molyneaux L, Constantino M, Twigg SM, Yue DK (2008) Timing is everything: age of onset influences long-term retinopathy risk in type 2 diabetes, independent of traditional risk factors. Diabetes Care 31:1985–1990PubMedCrossRef
4.
Zurück zum Zitat Ji L, Hou X, Han X (2001) Prevalence and clinical characteristics of mitochondrial tRNA leu(UUR) mt 3243 A→G and ND-1 gene mt 3316 G→A mutations in Chinese patients with type 2 diabetes. Chin Med J (Engl) 114:1205–1207 Ji L, Hou X, Han X (2001) Prevalence and clinical characteristics of mitochondrial tRNA leu(UUR) mt 3243 A→G and ND-1 gene mt 3316 G→A mutations in Chinese patients with type 2 diabetes. Chin Med J (Engl) 114:1205–1207
5.
Zurück zum Zitat Wiederkehr A, Wollheim CB (2006) Minireview: implication of mitochondria in insulin secretion and action. Endocrinology 147:2643–2649PubMedCrossRef Wiederkehr A, Wollheim CB (2006) Minireview: implication of mitochondria in insulin secretion and action. Endocrinology 147:2643–2649PubMedCrossRef
6.
Zurück zum Zitat Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671PubMedCrossRef Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350:664–671PubMedCrossRef
7.
Zurück zum Zitat Serradas P, Giroix MH, Saulnier C et al (1995) Mitochondrial deoxyribonucleic acid content is specifically decreased in adult, but not fetal, pancreatic islets of the Goto–Kakizaki rat, a genetic model of noninsulin-dependent diabetes. Endocrinology 136:5623–5631PubMedCrossRef Serradas P, Giroix MH, Saulnier C et al (1995) Mitochondrial deoxyribonucleic acid content is specifically decreased in adult, but not fetal, pancreatic islets of the Goto–Kakizaki rat, a genetic model of noninsulin-dependent diabetes. Endocrinology 136:5623–5631PubMedCrossRef
8.
Zurück zum Zitat Antonetti DA, Reynet C, Kahn CR (1995) Increased expression of mitochondrial-encoded genes in skeletal muscle of humans with diabetes mellitus. J Clin Invest 95:1383–1388PubMedCrossRef Antonetti DA, Reynet C, Kahn CR (1995) Increased expression of mitochondrial-encoded genes in skeletal muscle of humans with diabetes mellitus. J Clin Invest 95:1383–1388PubMedCrossRef
9.
Zurück zum Zitat Wang H, Hiatt WR, Barstow TJ, Brass EP (1999) Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease. Eur J Appl Physiol Occup Physiol 80:22–27PubMedCrossRef Wang H, Hiatt WR, Barstow TJ, Brass EP (1999) Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease. Eur J Appl Physiol Occup Physiol 80:22–27PubMedCrossRef
10.
Zurück zum Zitat Sukhorukov VS, Nartsissov RP, Petrichuk SV et al (2000) Comparative diagnostic value of the analysis of the skeletal muscle and lymphocytes in mitochondrial diseases. Arkh Patol 62:19–21PubMed Sukhorukov VS, Nartsissov RP, Petrichuk SV et al (2000) Comparative diagnostic value of the analysis of the skeletal muscle and lymphocytes in mitochondrial diseases. Arkh Patol 62:19–21PubMed
11.
Zurück zum Zitat Lee HK, Song JH, Shin CS et al (1998) Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 42:161–167PubMedCrossRef Lee HK, Song JH, Shin CS et al (1998) Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 42:161–167PubMedCrossRef
12.
Zurück zum Zitat Arkan MC, Hevener AL, Greten FR et al (2005) IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198PubMedCrossRef Arkan MC, Hevener AL, Greten FR et al (2005) IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198PubMedCrossRef
13.
Zurück zum Zitat Song J, Oh JY, Sung YA, Pak YK, Park KS, Lee HK (2001) Peripheral blood mitochondrial DNA content is related to insulin sensitivity in offspring of type 2 diabetic patients. Diabetes Care 24:865–869PubMedCrossRef Song J, Oh JY, Sung YA, Pak YK, Park KS, Lee HK (2001) Peripheral blood mitochondrial DNA content is related to insulin sensitivity in offspring of type 2 diabetic patients. Diabetes Care 24:865–869PubMedCrossRef
14.
Zurück zum Zitat ML McGill M, Yue DK, Turtle JR (1993) A single visit diabetes complication assessment service: a complement to diabetes management at the primary care level. Diabet Med 10:366–370CrossRef ML McGill M, Yue DK, Turtle JR (1993) A single visit diabetes complication assessment service: a complement to diabetes management at the primary care level. Diabet Med 10:366–370CrossRef
15.
Zurück zum Zitat Group ETDRSR (1991) Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 98(5 Suppl):786–806 Group ETDRSR (1991) Grading diabetic retinopathy from stereoscopic color fundus photographs—an extension of the modified Airlie House classification. ETDRS report number 10. Ophthalmology 98(5 Suppl):786–806
16.
Zurück zum Zitat Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15:539–553PubMedCrossRef
17.
Zurück zum Zitat Gourlain K, Amellal B, Ait Arkoub Z, Dupin N, Katlama C, Calvez V (2003) Quantitative analysis of human mitochondrial DNA using a real-time PCR assay. HIV Med 4:287–292PubMedCrossRef Gourlain K, Amellal B, Ait Arkoub Z, Dupin N, Katlama C, Calvez V (2003) Quantitative analysis of human mitochondrial DNA using a real-time PCR assay. HIV Med 4:287–292PubMedCrossRef
18.
Zurück zum Zitat Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45PubMedCrossRef Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45PubMedCrossRef
19.
Zurück zum Zitat Ochi M, Osawa H, Hirota Y et al (2007) Frequency of the G/G genotype of resistin single nucleotide polymorphism at 420 appears to be increased in younger-onset type 2 diabetes. Diabetes 56:2834–2838PubMedCrossRef Ochi M, Osawa H, Hirota Y et al (2007) Frequency of the G/G genotype of resistin single nucleotide polymorphism at 420 appears to be increased in younger-onset type 2 diabetes. Diabetes 56:2834–2838PubMedCrossRef
20.
Zurück zum Zitat Lehman DM, Hunt KJ, Leach RJ et al (2007) Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans. Diabetes 56:389–393PubMedCrossRef Lehman DM, Hunt KJ, Leach RJ et al (2007) Haplotypes of transcription factor 7-like 2 (TCF7L2) gene and its upstream region are associated with type 2 diabetes and age of onset in Mexican Americans. Diabetes 56:389–393PubMedCrossRef
21.
Zurück zum Zitat Guo Y, Traurig M, Ma L et al (2006) CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians. Diabetes 55:3625–3629PubMedCrossRef Guo Y, Traurig M, Ma L et al (2006) CHRM3 gene variation is associated with decreased acute insulin secretion and increased risk for early-onset type 2 diabetes in Pima Indians. Diabetes 55:3625–3629PubMedCrossRef
22.
Zurück zum Zitat Jaakkola U, Pesonen U, Vainio-Jylha E, Koulu M, Pollonen M, Kallio J (2006) The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy. Exp Clin Endocrinol Diabetes 114:147–152PubMedCrossRef Jaakkola U, Pesonen U, Vainio-Jylha E, Koulu M, Pollonen M, Kallio J (2006) The Leu7Pro polymorphism of neuropeptide Y is associated with younger age of onset of type 2 diabetes mellitus and increased risk for nephropathy in subjects with diabetic retinopathy. Exp Clin Endocrinol Diabetes 114:147–152PubMedCrossRef
23.
Zurück zum Zitat Flavell DM, Ireland H, Stephens JW et al (2005) Peroxisome proliferator-activated receptor α gene variation influences age of onset and progression of type 2 diabetes. Diabetes 54:582–586PubMedCrossRef Flavell DM, Ireland H, Stephens JW et al (2005) Peroxisome proliferator-activated receptor α gene variation influences age of onset and progression of type 2 diabetes. Diabetes 54:582–586PubMedCrossRef
24.
Zurück zum Zitat Zeggini E, Parkinson J, Halford S et al (2004) Association studies of insulin receptor substrate 1 gene (irs1) variants in type 2 diabetes samples enriched for family history and early age of onset. Diabetes 53:3319–3322PubMedCrossRef Zeggini E, Parkinson J, Halford S et al (2004) Association studies of insulin receptor substrate 1 gene (irs1) variants in type 2 diabetes samples enriched for family history and early age of onset. Diabetes 53:3319–3322PubMedCrossRef
25.
Zurück zum Zitat Oliva R, Novials A, Sánchez M et al (2004) The HFE gene is associated to an earlier age of onset and to the presence of diabetic nephropathy in diabetes mellitus type 2. Endocr 24:111–114CrossRef Oliva R, Novials A, Sánchez M et al (2004) The HFE gene is associated to an earlier age of onset and to the presence of diabetic nephropathy in diabetes mellitus type 2. Endocr 24:111–114CrossRef
26.
Zurück zum Zitat Wiltshire S, Frayling TM, Groves CJ et al (2004) Evidence from a large U.K. family collection that genes influencing age of onset of type 2 diabetes map to Chromosome 12p and to the MODY3/NIDDM2 Locus on 12q24. Diabetes 53:855–860PubMedCrossRef Wiltshire S, Frayling TM, Groves CJ et al (2004) Evidence from a large U.K. family collection that genes influencing age of onset of type 2 diabetes map to Chromosome 12p and to the MODY3/NIDDM2 Locus on 12q24. Diabetes 53:855–860PubMedCrossRef
27.
Zurück zum Zitat Hanson RL, Bogardus C, Duggan D et al (2007) A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array. Diabetes 56:3045–3052PubMedCrossRef Hanson RL, Bogardus C, Duggan D et al (2007) A search for variants associated with young-onset type 2 diabetes in American Indians in a 100K genotyping array. Diabetes 56:3045–3052PubMedCrossRef
28.
Zurück zum Zitat Curran JE, Johnson MP, Dyer TD et al (2007) Genetic determinants of mitochondrial content. Hum Mol Genet 16:1504–1514PubMedCrossRef Curran JE, Johnson MP, Dyer TD et al (2007) Genetic determinants of mitochondrial content. Hum Mol Genet 16:1504–1514PubMedCrossRef
29.
Zurück zum Zitat Silva JP, Kohler M, Graff C et al (2000) Impaired insulin secretion and β-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 26:336–340PubMedCrossRef Silva JP, Kohler M, Graff C et al (2000) Impaired insulin secretion and β-cell loss in tissue-specific knockout mice with mitochondrial diabetes. Nat Genet 26:336–340PubMedCrossRef
30.
31.
Zurück zum Zitat Hevener AL, Olefsky JM, Reichart D et al (2007) Macrophage PPAR γ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117:1658–1669PubMedCrossRef Hevener AL, Olefsky JM, Reichart D et al (2007) Macrophage PPAR γ is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones. J Clin Invest 117:1658–1669PubMedCrossRef
32.
Zurück zum Zitat Ehses JA, Perren A, Eppler E et al (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–2370PubMedCrossRef Ehses JA, Perren A, Eppler E et al (2007) Increased number of islet-associated macrophages in type 2 diabetes. Diabetes 56:2356–2370PubMedCrossRef
33.
Zurück zum Zitat Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407PubMedCrossRef Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407PubMedCrossRef
34.
Zurück zum Zitat Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964PubMedCrossRef Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964PubMedCrossRef
35.
Zurück zum Zitat Heine GH, Ulrich C, Seibert E et al (2007) CD14++CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients. Kidney Int 73:622–629PubMedCrossRef Heine GH, Ulrich C, Seibert E et al (2007) CD14++CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients. Kidney Int 73:622–629PubMedCrossRef
36.
Zurück zum Zitat Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef Brownlee M (2005) The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54:1615–1625PubMedCrossRef
37.
Zurück zum Zitat Yu T, Robotham JL, Yoon Y (2006) Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A 103:2653–2658PubMedCrossRef Yu T, Robotham JL, Yoon Y (2006) Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A 103:2653–2658PubMedCrossRef
38.
Zurück zum Zitat Baughman JM, Mootha VK (2006) Buffering mitochondrial DNA variation. Nat Genet 38:1232–1233PubMedCrossRef Baughman JM, Mootha VK (2006) Buffering mitochondrial DNA variation. Nat Genet 38:1232–1233PubMedCrossRef
39.
Zurück zum Zitat Moreno-Loshuertos R, Acin-Perez R, Fernandez-Silva P et al (2006) Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants. Nat Genet 38:1261–1268PubMedCrossRef Moreno-Loshuertos R, Acin-Perez R, Fernandez-Silva P et al (2006) Differences in reactive oxygen species production explain the phenotypes associated with common mouse mitochondrial DNA variants. Nat Genet 38:1261–1268PubMedCrossRef
40.
Zurück zum Zitat Nisoli E, Carruba MO (2006) Nitric oxide and mitochondrial biogenesis. J Cell Sci 119:2855–2862PubMedCrossRef Nisoli E, Carruba MO (2006) Nitric oxide and mitochondrial biogenesis. J Cell Sci 119:2855–2862PubMedCrossRef
41.
Zurück zum Zitat Tedesco L, Valerio A, Cervino C et al (2008) Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through endothelial nitric oxide synthase expression in white adipocytes. Diabetes 57:2028–2036PubMedCrossRef Tedesco L, Valerio A, Cervino C et al (2008) Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through endothelial nitric oxide synthase expression in white adipocytes. Diabetes 57:2028–2036PubMedCrossRef
42.
Zurück zum Zitat Schick BA, Laaksonen R, Frohlich JJ et al (2007) Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin. Clin Pharmacol Ther 81:650–653PubMedCrossRef Schick BA, Laaksonen R, Frohlich JJ et al (2007) Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin. Clin Pharmacol Ther 81:650–653PubMedCrossRef
43.
Zurück zum Zitat Bogacka I, Xie H, Bray GA, Smith SR (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54:1392–1399PubMedCrossRef Bogacka I, Xie H, Bray GA, Smith SR (2005) Pioglitazone induces mitochondrial biogenesis in human subcutaneous adipose tissue in vivo. Diabetes 54:1392–1399PubMedCrossRef
44.
Zurück zum Zitat Singh R, Hattersley AT, Harries LW (2007) Reduced peripheral blood mitochondrial DNA content is not a risk factor for type 2 diabetes. Diabet Med 24:784–787PubMedCrossRef Singh R, Hattersley AT, Harries LW (2007) Reduced peripheral blood mitochondrial DNA content is not a risk factor for type 2 diabetes. Diabet Med 24:784–787PubMedCrossRef
Metadaten
Titel
Mitochondrial DNA content in peripheral blood monocytes: relationship with age of diabetes onsetand diabetic complications
verfasst von
J. Wong
S. V. McLennan
L. Molyneaux
D. Min
S. M. Twigg
D. K. Yue
Publikationsdatum
01.09.2009
Verlag
Springer-Verlag
Erschienen in
Diabetologia / Ausgabe 9/2009
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-009-1424-6

Weitere Artikel der Ausgabe 9/2009

Diabetologia 9/2009 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.