Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

Rasmus Rabøl; Patricia M V Højberg; Thomas Almdal; Robert Boushel; Steen B Haugaard; Sten Madsbad; Flemming Dela; Rasmus Rabøl; Patricia M V Højberg; Thomas Almdal; Robert Boushel; Steen B Haugaard; Sten Madsbad; Flemming Dela

doi:10.1210/jc.2008-1475

Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

Rasmus Rabøl, Patricia M V Højberg, Thomas Almdal, Robert Boushel, Steen B Haugaard, Sten Madsbad, Flemming Dela, Rasmus Rabøl, Patricia M V Højberg, Thomas Almdal, Robert Boushel, Steen B Haugaard, Sten Madsbad, Flemming Dela

49 Citations (Scopus)

Abstract

AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM. PATIENTS AND METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM. DISCUSSION: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	94
Issue number	4
Pages (from-to)	1372-78
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2008-1475 https://doi.org/10.1210/jc.2008-1475
Publication status	Published - 2009

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Rabøl, R., Højberg, P. M. V., Almdal, T., Boushel, R., Haugaard, S. B., Madsbad, S., Dela, F., Rabøl, R., Højberg, P. M. V., Almdal, T., Boushel, R., Haugaard, S. B., Madsbad, S., & Dela, F. (2009). Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes. Journal of Clinical Endocrinology and Metabolism, 94(4), 1372-78. https://doi.org/10.1210/jc.2008-1475, https://doi.org/10.1210/jc.2008-1475

Rabøl, R, Højberg, PMV, Almdal, T, Boushel, R, Haugaard, SB, Madsbad, S , Dela, F, Rabøl, R, Højberg, PMV, Almdal, T, Boushel, R, Haugaard, SB, Madsbad, S & Dela, F 2009, 'Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 4, pp. 1372-78. https://doi.org/10.1210/jc.2008-1475, https://doi.org/10.1210/jc.2008-1475

@article{2f5653c05f2c11dea8de000ea68e967b,

title = "Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes",

abstract = "AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM. PATIENTS AND METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM. DISCUSSION: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.",

author = "Rasmus Rab{\o}l and H{\o}jberg, {Patricia M V} and Thomas Almdal and Robert Boushel and Haugaard, {Steen B} and Sten Madsbad and Flemming Dela and Rasmus Rab{\o}l and H{\o}jberg, {Patricia M V} and Thomas Almdal and Robert Boushel and Haugaard, {Steen B} and Sten Madsbad and Flemming Dela",

note = "Keywords: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructosamine; Hemoglobin A, Glycosylated; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, NPH; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption",

year = "2009",

doi = "10.1210/jc.2008-1475",

language = "English",

volume = "94",

pages = "1372--78",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "4",

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TY - JOUR

T1 - Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

AU - Rabøl, Rasmus

AU - Højberg, Patricia M V

AU - Almdal, Thomas

AU - Boushel, Robert

AU - Haugaard, Steen B

AU - Madsbad, Sten

AU - Dela, Flemming

AU - Rabøl, Rasmus

AU - Højberg, Patricia M V

AU - Almdal, Thomas

AU - Boushel, Robert

AU - Haugaard, Steen B

AU - Madsbad, Sten

AU - Dela, Flemming

N1 - Keywords: Adult; Aged; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Fructosamine; Hemoglobin A, Glycosylated; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Insulin, NPH; Male; Middle Aged; Mitochondria, Muscle; Muscle, Skeletal; Oxygen Consumption

PY - 2009

Y1 - 2009

N2 - AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM. PATIENTS AND METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM. DISCUSSION: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.

AB - AIM: Skeletal muscle mitochondrial content is reduced in type 2 diabetes mellitus (T2DM). Whether hyperglycemia inhibits mitochondrial biogenesis and/or function is unknown. This study examined the effect of different levels of glycemia on skeletal muscle mitochondrial function in patients with T2DM. PATIENTS AND METHODS: Eleven patients with T2DM [9 males, 2 females; age, 52.8 +/- 2.5 yr (mean +/- se); body mass index, 30.2 +/- 1.1 kg/m(2)] in poor glycemic control were treated with insulin aspart and NPH insulin for a median period of 46 d (range, 31-59). Mitochondrial respiration and citrate synthase activity (a marker of mitochondrial content) were measured before and after treatment. Eleven healthy subjects (age, 53.3 +/- 2.7 yr; body mass index, 30.6 +/- 1.1 kg/m(2)) were included as controls. RESULTS: Hemoglobin A1c (9.1 +/- 0.5 to 7.5 +/- 0.3%; P < 0.001) and fasting plasma glucose (12.7 +/- 1.1 to 6.5 +/- 0.3 mmol/liter; P < 0.001) were reduced after treatment. Mitochondrial respiration per milligram muscle was lower in T2DM compared to controls [substrates for complex I, 24% lower (P < 0.05); substrates for complex I+II, 17% lower (P < 0.05)]. Mitochondrial respiration and citrate synthase activity did not differ before and after improvements in glycemic control, but mitochondrial respiration correlated with fasting plasma glucose before (r(2) = 0.53; P < 0.05) but not after treatment [r(2) = 0.0024; not significant (NS)]. Mitochondrial respiration normalized to mitochondrial content did not differ between control subjects and patients with T2DM. DISCUSSION: Mitochondrial respiration and content was not improved after significant improvements in glycemic control. However, severe hyperglycemia inhibited respiration reversibly, but moderate hyperglycemia and mitochondrial function were not correlated.

U2 - 10.1210/jc.2008-1475

DO - 10.1210/jc.2008-1475

M3 - Journal article

C2 - 19141588

SN - 0021-972X

VL - 94

SP - 1372

EP - 1378

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 4

ER -

Effect of Hyperglycemia on Mitochondrial Respiration in Type 2 Diabetes

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