Intramuscular triglyceride content is increased in IDDM

Abstract

Increased lipid oxidation is related to insulin resistance [1]. Most of the fatty acids taken up by resting muscle are not oxidized directly, but enter an intramuscular pool with a slow turnover at rest and are the immediate source of lipid substrate for oxidation [2]. The NEFA taken up by muscle are incorporated to lipid droplets in muscle and 70--90 % of fatty acids entering the muscle are rapidly esterified to triglyceride (TG) [3]. For example, raising extracellular palmitate increases esterification, but does not increase intramuscular concentration of palmitate [4]. Part of the enhanced lipid oxidation can be derived from intramuscular sources [5].As compared to healthy subjects a sixfold increase of muscle (m) TG in patients with non-insulin-dependent diabetes mellitus [6], and a sevenfold increase in TG content in striated muscle in coronary bypass-operated patients with impaired glucose tolerance [7] have been reported in comparison to control groups. These patient groups are also characterized by insulin resistance. Sustained euglycaemic hyperinsulinaemia Diabetologia (1998) Summary Increased lipid oxidation is related to insulin resistance. Some of the enhanced lipid utilization may be derived from intramuscular sources. We studied muscle triglyceride (mTG) concentration and its relationship to insulin sensitivity in 10 healthy men (age 29 ± 2 years, BMI 23.3 ± 0.6 kg/m 2 ) and 17 men with insulin-dependent diabetes mellitus (IDDM) (age 30 ± 2 years, BMI 22.8 ± 0.5 kg/m 2 , diabetes duration 14 ± 2 years, HbA 1 c 7.7 ± 0.3 %, insulin dose 48 ± 3 U/day). Insulin sensitivity was measured with a 4 h euglycaemic (5 mmol/l) hyperinsulinaemic (1.5 mU or 9 pmol ⋅ kg --1 ⋅ min --1 ) clamp accompanied by indirect calorimetry before and at the end of the insulin infusion. A percutaneous biopsy was performed from m. vastus lateralis for the determination of mTG. At baseline the IDDM patients had higher glucose (10.2 ± 0.9 vs 5.6 ± 0.1 mmol/l, p < 0.001), insulin (40.3 ± 3.2 vs 23.2 ± 4.2 pmol/l, p < 0.01), HDL cholesterol (1.28 ± 0.06 vs 1.04 ± 0.03 mmol/l, p < 0.01) and mTG (32.9 ± 4.6 vs 13.6 ± 2.7 mmol/kg dry weight, p < 0.01) concentrations than the healthy men, respectively. The IDDM patients had lower insulin stimulated whole body total (--25 %, p < 0.001), oxidative (--18 %, p < 0.01) and non-oxidative glucose disposal rates (--43 %, p < 0.001), whereas lipid oxidation rate was higher in the basal state ( + 44 %, p < 0.01) and during hyperinsulinaemia ( + 283 %, p < 0.05). mTG concentrations did not change significantly during the clamp or correlate with insulin stimulated glucose disposal. In healthy men mTG correlated positively with lipid oxidation rate at the end of hyperinsulinaemia (r = 0.75, p < 0.05). In conclusion: 1) IDDM is associated with increased intramuscular TG content. 2) mTG content does not correlate with insulin sensitivity in healthy subjects or patients with IDDM. [Diabetologia (1998) 41: 111--115]

Muscle adiposity and body fat distribution in type 1 and type 2 diabetes: varying relationships according to diabetes type

“…Thus, minimizing hyperglycemia by achieving recommended glycemic control might help to normalize the potential muscle fat abnormalities observed in type 1 diabetic subjects. However, the results from the present study and those of Ebeling et al 12 and Perseghin et al…”

“…In the Ebeling et al 12 study, where subjects had better metabolic control (mean HbA 1c of 7.7%), no relation between muscle fat and insulin resistance was found. In the present study, no relationship was found between muscle lipids, estimated by CT scan, and HbA 1c .…”

“…To our knowledge, only two studies have examined the relationships between insulin sensitivity and muscle lipid content in type 1 diabetes and have presented conflicting results. 11,12 Perseghin et al 11 showed a positive association between intramyocellular lipid content (IMCL) and insulin resistance suggesting that accretion of lipids within skeletal muscle is a marker of insulin resistance in type 1 diabetes, while Ebeling et al 12 did not shown this relationship. This discrepancy may be explained by the method of assessment of the muscle lipids (magnetic resonance spectroscopy vs biopsy) and/or by the degree of glycemic control (HbA 1c values of 8.6 vs 7.7%).…”

Effect of Training on Muscle Triacylglycerol and Structural Lipids

“…However, in single, homogeneous groups of subjects (9,(33)(34)(35) in the present study and in normoglycemic obese subjects (31), the inverse relationship between muscle triacylglycerol stores (measured by muscle biopsy, NMR, and Oil red O) and insulin sensitivity is normally not present, although exceptions exist (10,36). As for the extramyocellular triacylglycerol stores (fat and adipose cells stored outside the myofibrils but within the muscle fascia), most but not all studies (9) find no relation to insulin sensitivity (11,12,37).…”

Rates of skeletal muscle and adipose tissue glycerol release in nonobese and obese subjects.

“…Furthermore, an inverse relationship between the amount of TG deposited in muscle and sensitivity to insulin-induced glucose uptake has been recently observed in the normal state and in various insulin-resistant conditions (14)(15)(16)(17)(18). These findings suggest that FFAs derived from skeletal muscle lipolysis may be an important endogenous energy source and indicate that increased TG deposition and enhanced lipolysis and FFA mobilization/oxidation in skeletal muscle are important in the pathogenesis of peripheral insulin resistance via interactions between glucose and FFA utilization in muscle cells.…”