scholarly journals Ketone Bodies Are Mildly Elevated in Subjects with Type 2 Diabetes Mellitus and Are Inversely Associated with Insulin Resistance as Measured by the Lipoprotein Insulin Resistance Index

2020 ◽  
Vol 9 (2) ◽  
pp. 321 ◽  
Author(s):  
Erwin Garcia ◽  
Irina Shalaurova ◽  
Steven P. Matyus ◽  
David N. Oskardmay ◽  
James D. Otvos ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Mass Spectrometry ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ketone Bodies ◽  
Linear Regression Analysis ◽  
Resistance Index ◽  
Insulin Resistance Index

Background: Quantifying mildly elevated ketone bodies is clinically and pathophysiologically relevant, especially in the context of disease states as well as for monitoring of various diets and exercise regimens. As an alternative assay for measuring ketone bodies in the clinical laboratory, a nuclear magnetic resonance (NMR) spectroscopy-based test was developed for quantification of β-hydroxybutyrate (β-HB), acetoacetate (AcAc) and acetone. Methods: The ketone body assay was evaluated for precision, linearity and stability and method comparisons were performed. In addition, plasma ketone bodies were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1198; 373 type 2 diabetes mellitus (T2DM) subjects). Results: β-HB and AcAc quantified using NMR and mass spectrometry and acetone quantified using NMR and gas chromatography/mass spectrometry were highly correlated (R2 = 0.996, 0.994, and 0.994 for β-HB, AcAc, acetone, respectively). Coefficients of variation (%CVs) for intra- and inter-assay precision ranged from 1.3% to 9.3%, 3.1% to 7.7%, and 3.8% to 9.1%, for β-HB, AcAc and acetone, respectively. In the IRAS, ketone bodies were elevated in subjects with T2DM versus non-diabetic individuals (p = 0.011 to ≤0.001). Age- and sex-adjusted multivariable linear regression analysis revealed that total ketone bodies and β-HB were associated directly with free fatty acids (FFAs) and T2DM and inversely with triglycerides and insulin resistance as measured by the Lipoprotein Insulin Resistance Index. Conclusions: Concentrations of the three main ketone bodies can be determined by NMR with good clinical performance, are elevated in T2DM and are inversely associated with triglycerides and insulin resistance.

Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus

2001 ◽  
Vol 280 (1) ◽  
pp. E23-E30 ◽  
Author(s):  
Guenther Boden ◽  
Xinhua Chen ◽  
T. Peter Stein
Keyword(s):  
Diabetes Mellitus ◽  
Mass Spectrometry ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endogenous Glucose Production ◽  
Gas Chromatography Mass Spectrometry ◽  
Entire Group ◽  
Insulin Deficiency

We tested the generally accepted concept that increased gluconeogenesis (GNG) and endogenous glucose production (EGP) are the main reasons for postabsorptive hyperglycemia in patients with type 2 diabetes mellitus (T2DM). GNG was measured with the 2H2O method by use of both the C5-to-C2 ratio (C5/C2, with gas chromatography-mass spectrometry) and the C5-to-2H2O ratio (C5/2H2O, with isotope ratio mass spectrometry), and EGP was measured with 3-[3H]glucose in 27 patients with T2DM [13 with fasting plasma glucose (FPG) >10 mM and 14 with FPG <10 mM] and in 7 weight- and age-matched nondiabetic controls. The results showed 1) that GNG could be determined accurately with 2H2O by using either C5/C2 or C5/2H2O; 2) that whereas after an overnight fast of 16 h, GNG was higher in the entire group of patients with T2DM than in controls (6.4 vs. 5.0 μmol · kg−1 · min−1 or 60.4 vs. 51.4% of EGP, P < 0.02), GNG was within normal limits (less than the mean ± 2 SD of controls or <65.3%) in 11/14 (79%) patients with mild to moderate hyperglycemia (FPG <10 mM) and in 5/13 (38%) of patients with severe hyperglycemia (FPG 10–20 mM); 3) that elevated GNG in T2DM was associated with a 43% decrease in prehepatic insulin secretion, i.e., with hepatic insulin deficiency; and 4) that FPG correlated significantly with glucose clearance (insulin resistance) ( r = 0.70) and with GNG ( r = 0.50) or EGP ( r = 0.45). We conclude 1) that peripheral insulin resistance is at least as important as GNG (and EGP) as a cause of postabsorptive hyperglycemia in T2DM and 2) that GNG and EGP in T2DM are increased under conditions of significant hepatic insulin deficiency and thus probably represent a late event in the course of T2DM.

scholarly journals Evidence for Training-Induced Changes in miRNA Levels in the Skeletal Muscle of Patients With Type 2 Diabetes Mellitus

2020 ◽  
Vol 11 ◽  
Author(s):  
Sarah Simaitis ◽  
Benedikt Schulte-Körne ◽  
Thorsten Schiffer ◽  
Wilhelm Bloch ◽  
Hans-Georg Predel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Type 2 Diabetes Mellitus ◽  
Glycemic Control ◽  
Resistance Index ◽  
Micro Rnas ◽  
Study Results

Physical training can improve glycemic control in patients with type 2 diabetes mellitus (T2DM). However, the underlying mechanisms are not entirely clear. An interesting piece of the puzzle could be the regulation of micro-RNAs (miRNAs). They are important modulators of protein expression. Some miRNAs were found to be both linked to poor glycemic control/insulin resistance (with evidence from in vivo and/or in vitro studies) and dysregulated in the skeletal muscle of T2DM patients. This pilot study examines whether a 3-month endurance training program [three times a week, 70–80% peak heart rate (HRpeak)] can down-regulate their levels in T2DM men (n = 7). One skeletal muscle biopsy sample was obtained from each patient at T1 (6 weeks pre-intervention), one at T2 (1 week pre-intervention) and one at T3 (3–4 days post-intervention). miRNA-27a-3p, −29a-3p, −29b-3p, −29c-3p, −106b-5p, −135a-5p, −143-3p, −144-3p, −194-5p, and − 206 levels were determined by RT-qPCR. Friedman ANOVA and post-hoc tests showed that miRNA-29b-3p, −29c-3p and -135a-5p levels were significantly reduced post-training (T3 vs. T2 and/or T1). Glycated hemoglobin (HbA1c) and HOMA insulin resistance index did not change significantly. However, HbA1c was reduced in 6 of 7 patients post-training. Furthermore, Spearman’s rank correlation analyses with all values from all time points showed significant negative associations between miRNA-29c-3p, −106b-5p, −144-3p and −194-5p levels and cardiorespiratory fitness (VO2peak). The study results imply that regular exercise and improving one’s physical fitness is helpful for the regulation of skeletal muscle miRNAs in T2DM patients. Whether or not changes in the miRNA profile can affect the clinical situation of T2DM patients warrants further research.

Trabecular bone score and insulin resistance in type 2 diabetes mellitus

2020 ◽  
Author(s):  
Ponce Maria Hayon ◽  
Laguna Mª del Carmen Serrano ◽  
Perez Maria Dolores Aviles ◽  
Beatriz Garcia Fontana ◽  
Sheila Gonzalez Salvatierra ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Trabecular Bone ◽  
Trabecular Bone Score
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