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

Abstract

Aims/hypothesis Both inherited and acquired insulin resistance have been associated with abnormal muscle mitochondrial function. At whole-body level, maximal oxygen uptake (V : O 2max ) and/or metabolic flexibility (as given by ΔRQ) reflect certain features of mitochondrial function. This study tests the hypotheses (1) that V : O 2max and ΔRQ correlate tightly with each other and with insulin sensitivity and (2) that glycaemia, lipidaemia or subclinical inflammation would explain such relationships. Methods Near-normoglycaemic individuals with type 2 diabetes mellitus (n = 136) with a short known disease duration (<12 months) underwent cycling spiroergometry, indirect calorimetry and hyperinsulinaemic-euglycaemic clamp tests. Results Both V : O 2max (r = 0.39, p < 0.0001) and ΔRQ (r = 0.32, p < 0.0001) correlated positively with whole-body insulin sensitivity, even after adjusting for anthropometric variables, glycaemia and glucose-lowering medication, but not after adjusting for NEFA. V : O 2max further correlated negatively with circulating high-sensitivity C-reactive protein concentration. However, V : O 2max did not relate to ΔRQ, even after adjusting for whole-body insulin sensitivity.

Differential Patterns of Impaired Cardiorespiratory Fitness and Cardiac Autonomic Dysfunction in Recently Diagnosed Type 1 and Type 2 Diabetes

“…In patients with insulin resistant type 2 diabetes, molecular impairments as well as morphological alterations lead to a decrease of mitochondrial activity and oxidative phosphorylation capacity (21). A recent study indirectly supports this notion by showing a positive correlation between insulin sensitivity and VO 2max in patients with recently diagnosed type 2 diabetes (30). On the other hand, disturbed vascular dynamics caused by autonomic dysfunction might lead to an impaired peripheral blood flow to skeletal muscles as well as to diminished cardiac output and, subsequently, to reduced CRF (4).…”

From the past to future: from energy expenditure to energy intake to energy expenditure

“…24, 25, 26 When compared with EI, research on EE downsized during the last decades leaving a relatively small number of experts in this area only. However, research on EE is still challenging and currently relates to (i) metabolic adaptation to negative energy balance, 27, 28 (ii) mitochondrial metabolism associated with aging, obesity and type 2 diabetes mellitus, 29, 30, 31, 32, 33, 34, 35, 36 (iii) the role of REE in hunger and appetite control, 37 (iv) non-shivering thermogenesis and brown adipose tissue, 38, 39, 40 (v) cellular bioenergetics as a target of obesity treatment 41 and (vi) on the evolutionary and ecological determinants of TEE in humans and other primates. 42 It is obvious that there is still need to think about both sides of the energy balance.…”

Specific Hepatic Sphingolipids Relate to Insulin Resistance, Oxidative Stress, and Inflammation in Nonalcoholic Steatohepatitis

“…Briefly, participants were asked to refrain from physical activity for 3 days before the clamp test. The patient with T2D withdrew oral glucose-lowering medication for 3 days before the test (19). On the day of the test and 1 week before surgery, participants arrived at the clinical research center at 0800 h, where they received two venous catheters in the antecubital veins of both arms for blood sampling and infusions of glucose and insulin.…”

“…Blood glucose measurements were performed every 5 min, and a 20% dextrose infusion labeled with D- [6, H 2 ]glucose (2% enriched) was adjusted to maintainnormoglycemia(5mmol/L). Whole-body insulin sensitivity was measured from whole-body mean glucose infusion rates (M value) with glucose space correction (19). The hepatic insulin sensitivity index (HIS) was calculated as the quotient of 100/(fasting EGP 3 fasting insulin concentration), and insulin-mediated EGP suppression was calculated as 100 3 clamp EGP/fasting EGP (20).…”