Metabolic flexibility and oxidative capacity independently associate with insulin sensitivity in individuals with newly diagnosed type 2 diabetes

Abstract Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity. Methods In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n = 11), obese participants without diabetes (n = 12), lean individuals (n = 10) and endurance-trained athletes (n = 12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue. Results Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6 ± 4.0 and 56.7 ± 7.2 vs 21.8 ± 2.5 and 25.1 ± 4.3 years, p < 0.001, respectively) and displayed a higher BMI (32.4 ± 3.7 and 31.0 ± 3.7 vs 22.1 ± 1.8 and 21.0 ± 1.5 kg/m2, p < 0.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86 ± 0.79 vs 0.79 ± 0.51 AU, p = 0.002; and OPA1: 1.55 ± 0.64 vs 0.76 ± 0.52 AU, p = 0.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (n = 6). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (p = 0.048) and type 2 diabetes (p = 0.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (r = 0.48, p = 0.0001; r = 0.55, p < 0.001 and r = 0.61, p < 0.0001, respectively) and insulin sensitivity (r = 0.40, p = 0.008; r = 0.44, p = 0.003 and r = 0.48, p = 0.001, respectively). Conclusions/interpretation Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity. Clinical Trial registry numbers NCT00943059, NCT01298375 and NL1888

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Reduction of non-esterified fatty acids improves insulin sensitivity and lowers oxidative stress, but fails to restore oxidative capacity in type 2 diabetes: a randomised clinical trial

Diabetologia ◽

10.1007/s00125-013-3127-2 ◽

2013 ◽

Vol 57 (3) ◽

pp. 572-581 ◽

Cited By ~ 29

Author(s):

Esther Phielix ◽

Tomas Jelenik ◽

Peter Nowotny ◽

Julia Szendroedi ◽

Michael Roden

Keyword(s):

Oxidative Stress ◽

Type 2 Diabetes ◽

Clinical Trial ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Randomised Clinical Trial ◽

Oxidative Capacity ◽

Esterified Fatty Acids

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The Relationship between Serum 25-Hydroxy Vitamin D and Insulin Sensitivity and β-Cell Function in Newly Diagnosed Type 2 Diabetes

Journal of Diabetes Research ◽

10.1155/2015/636891 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Yuan Gao ◽

Xinchi Wu ◽

Qi Fu ◽

Yanyun Li ◽

Tao Yang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Vitamin D ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Newly Diagnosed ◽

25 Hydroxy Vitamin D ◽

The Relationship ◽

Diabetes Patients

The aim of this study was to investigate the relationship between serum 25-hydroxy vitamin D (25-OHD) and insulin sensitivity andβ-cell function in newly diagnosed type 2 diabetes. 395 newly diagnosed type 2 diabetes patients were enrolled in this study. Venous blood samples were collected at 0 min, 30 min, and 120 min of OGTT to measure serum glucose and insulin. Matsuda ISI and HOMA-IR were used to determine insulin sensitivity. The ratio of 0–120 min area under curve of insulin to glucose (insulin release index, INSR) was calculated as surrogate index ofβ-cell insulin secretion function. The products of insulin secretion indices multiplied by Matsuda insulin sensitivity index were used as disposition indices. Patients were divided into three groups according to tertiles (T1, T2, and T3) of 25-OHD concentration. There was significant difference among three groups for HOMA-IR, Matsuda ISI, and INSR. HOMA-IR, Matsuda ISI, INSR, and DI were undifferentiated among three groups in male patients. But HOMA-IR, Matsuda ISI, and INSR were significantly different among three groups in female patients after being adjusted by confounding factors. In conclusion, serum 25-OHD is associated with insulin sensitivity andβ-cell function for female newly diagnosed type 2 diabetes patients, and the association is ambiguous in males.

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Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research)

Journal of Diabetes Research ◽

10.1155/2016/9270768 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

Guang Yang ◽

Chunlin Li ◽

Yanping Gong ◽

Fusheng Fang ◽

Hui Tian ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Normal Glucose Tolerance ◽

Newly Diagnosed ◽

Factors Influencing ◽

Sensitivity Indices ◽

Normal Glucose

Aim.To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM).Methods.5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed.Results.TheMvalues of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg·kg−1·min−1, 6.23 ± 1.73 mg·kg−1·min−1, 6.37 ± 2.12 mg·kg−1·min−1, and 6.19 ± 1.89 mg·kg−1·min−1, respectively.Mvalues in HINS, IGT, and T2DM groups were lower than those in the NGT group (P=0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P=0.835). The independent factors influencing theMvalue were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with theMvalue (P<0.01).Conclusion.IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS.

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