Abstract

The prevalence of obesity and metabolic syndrome increases in patients with type 1 diabetes mellitus (T1DM). In the general population this is linked with ectopic lipid accumulation in liver (HCL) and skeletal muscle (IMCL), representing hallmarks in the development of insulin resistance. Moreover, hepatic mitochondrial activity is lower in newly diagnosed patients with T1DM. If this precedes later development of diabetes related fatty liver disease is currently not known. This study aims to investigate energy metabolism in liver (kATP) and skeletal muscle (kCK) and its impact on HCL, IMCL, cardiac fat depots and heart function in 10 patients with long standing T1DM compared to 11 well-matched controls by 31P/1H magnetic resonance spectroscopy. HCL was almost 70% lower in T1DM compared to controls (6.9 ± 5% vs 2.1 ± 1.3%; p = 0.030). Also kATP was significantly reduced (0.33 ± 0.1 s−1vs 0.17 ± 0.1 s−1; p = 0.018). In T1DM, dose of basal insulin strongly correlated with BMI (r = 0.676, p = 0.032) and HCL (r = 0.643, p = 0.045), but not with kATP. In the whole cohort, HCL was significantly associated with BMI (r = 0.615, p = 0.005). In skeletal muscle kCK was lower in patients with T1DM (0.25 ± 0.05 s−1vs 0.31 ± 0–04 s−1; p = 0.039). No significant differences were found in IMCL. Cardiac fat depots as well as heart function were not different. Our results in patients with long standing T1DM show that HCL is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle.

Highlights

  • type 1 diabetes mellitus (T1DM) show that hepatocellular lipid content (HCL) is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle

  • HCL was almost 70% lower in T1DM compared to controls. kATP was significantly reduced by half in T1DM (Fig. 1)

  • Dose of basal insulin strongly correlated with body mass index (BMI) (r = 0.676, p = 0.032) and HCL (r = 0.643, p = 0.045), while no significant associations were observed for kATP and concentrations of phosphate compounds

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Summary

Introduction

T1DM show that HCL is lower compared to matched controls, despite reduced energy metabolism in liver and skeletal muscle. Despite substantial reductions in the incidence of diabetes related comorbidities, including retinopathy and nephropathy, due to intensive diabetes treatment and better glycemic control[4], overall mortality has remained substantially elevated even in patients with well controlled type 1 diabetes[5]. This increase in mortality is mainly due to cardiovascular diseases and is further enhanced with worsening of glycaemia[5]. In non-diabetic individuals, as well as in patients suffering from type 2 diabetes mellitus (T2DM), ectopic lipid deposition in liver and skeletal muscle represent hallmarks in the development of insulin resistance. A prevalence of non-alcoholic fatty liver disease (NAFLD) up to 50%7,8, studies using proton magnetic resonance spectroscopy (1H MRS) showed a significantly lower hepatocellular lipid content (HCL) in obese patients with T1DM compared to non-diabetic control subjects[9,10]

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