Type 2 Diabetes Liver Research Articles

Relationships between plasma lactate, plasma alanine, genetic variations in lactate transporters and type 2 diabetes in the Japanese population

The present study aimed to characterize the relationships between plasma lactate, plasma alanine, monocarboxylate transporter (MCT) polymorphisms, and indices of diabetes in patients with type 2 diabetes (T2D) in Japan. Eighty-three patients with T2D were prospectively enrolled. The gluconeogenesis and glycogenolysis are enhanced and uptake of glucose is decreased in the T2D liver. Since the liver plays an important role in maintaining glucose metabolism, we examined the relationships between liver enzymes and indices of diabetes. Some studies have reported that MCT1 (SLC16A1) polymorphism causes metabolic diseases. In addition, a high frequency of MCT1 polymorphism was reported in a healthy Japanese population. However, little is known about the relationships between T2D and MCT polymorphisms. Plasma l-lactate concentration positively correlated with indices of diabetes (fasting plasma glucose [FPG] and hemoglobin A1c [HbA1c]) and with the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (γ-GTP). MCT1 polymorphisms were associated with all of these markers. We identified no significant correlations between d-lactate or alanine concentrations and any of these markers, but a significant association was observed between l-lactate, a marker of oxidative capacity, and indices of diabetes. We conclude that plasma l-lactate concentration may represent a predictor of the progression or severity of T2D.

Effects on Insulin Sensitivity, but Not on Mitochondrial Function Are Dependent on Insulin Resistance Status after High Intensity Interval Training

High intensity interval training (HIIT) is a time-efficient training approach to stimulate biogenesis in healthy populations. We hypothesized that HIIT would increase skeletal muscle insulin sensitivity due to improved muscle mitochondrial function in type 2 diabetes (T2D) patients and age- and BMI-matched controls (CON). We examined 18 sedentary male patients with T2D and 23 healthy male CON (age: 58±5 vs. 57±4 years, BMI: 31.4±2.4 vs. 30.4±2.3 kg.m-2) that were enrolled in a 12-week HIIT cycling protocol. CON were further grouped in insulin-sensitive (IS) and -resistant (IR) (baseline M in mg.kg-1.min-1; 7.4 ± 1.3 vs. 4.2 ± 1.1, p<0.001). Two-step hyperinsulinemic-euglycemic clamps, skeletal muscle biopsies for high resolution respirometry and magnetic resonance spectroscopy for liver fat quantification were performed. After 12 weeks of HIIT, T2D and IR CON increased their insulin sensitivity (3.9±1.9 vs. baseline: 2.7±1.6, p=0.02 and 5.5±2.1 vs. 4.2 ± 1.1, p=0.03, respectively), which returned to baseline after detraining. T2D and IR CON increased suppression of endogenous glucose production (EGP) during the high-insulin clamp (T2D: 91 ± 14% vs. baseline: 76 ± 11%, p=0.003 and IR CON: 107 ± 13% vs. 94 ± 14%, p=0.04). IR CON also increased suppression of lipolysis during the low-insulin clamp (82 ± 9 vs. 84 ± 8%, p=0.04). In T2D liver fat was decreased by 17% and remained decreased after detraining. Liver fat content remained unchanged by HIIT training in both CON groups. Muscle maximal uncoupled respiration increased in T2D and CON by 44% and 48%, respectively, at 12 weeks and remained increased after detraining in all groups (p<0.01). We conclude that at the same level of insulin resistance HIIT training improved hepatic and peripheral insulin sensitivity in patients with T2D and insulin resistant controls whereas changes in mitochondrial function occurred irrespective of insulin resistance status. Disclosure M. Apostolopoulou: None. D. Pesta: None. Y. Karusheva: None. S. Gancheva: None. T. Jelenik: None. A. Bierwagen: None. K. M ssig: None. J. Szendroedi: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi.