Metabolically Active Brown Adipose Tissue Is Found in Adult Subjects with Type 1 Diabetes.

Eriksson Eriksson,Berglund Berglund,Selvaraju Selvaraju,Espes Espes

doi:10.3390/ijms20235827

Abstract

Type 1 diabetes (T1D) is characterized by the loss of insulin-producing cells and hence insulin secretion and metabolic control. In addition to insulin, there are a number of hormones and cytokines that influence metabolism, and many of these can be secreted from brown adipose tissue (BAT). However, the presence and activity of BAT in T1D have not been studied, despite the fact that preclinical studies have shown that transplantation of BAT in mouse models of T1D can restore metabolic control. The metabolic activity of BAT, white adipose tissue (WAT), and skeletal muscle was investigated in patients with T1D (n = 11) by 2-deoxy-2-(18F)fluoro-D-glucose PET/CT after cold stimulation. Functional BAT was detected in 4 out of 11 individuals with T1D with a prevalence of 36%. The glucose utilization rate in the supraclavicular BAT regions ranged from 0.75–38.7 µmol × min−1 × 100 g−1. The glucose utilization per gram tissue was higher in BAT when compared with both WAT (p = 0.049) and skeletal muscle (p = 0.039). However, no correlation between BAT activity and metabolic control or insulin requirements was found. In conclusion, for the first time, cold-induced BAT was detected in patients with T1D with a wide range in metabolic activity. Contrary to findings in animal models, the metabolic activity of BAT had negligible impact on insulin requirements or metabolic control in T1D under normal physiological conditions.

Highlights

Type 1 diabetes (T1D) is characterized by a progressive loss of beta cells and thereby insulin secretion, resulting in hyperglycaemia
We found no correlation between metabolic activity of brown adipose tissue (BAT) and insulin requirements, whether expressed as total daily insulin doses (p = 0.83), weight adjusted (p = 0.64), or adjusted for lean body mass (p = 0.67) (Figure 3A)
BAT activity was not correlated to blood lipid profiles: total cholesterol (p = 0.72), HDL-cholesterol (p = 0.86), LDL-cholesterol (p = 0.58) or triglycerides (p = 0.78), nor did the metabolic activity of BAT correlate to body composition expressed as body mass (p = 0.71), Body Mass Index (BMI), fat mass (p = 0.93), or lean body mass (p = 0.71)

Summary

Introduction

Type 1 diabetes (T1D) is characterized by a progressive loss of beta cells and thereby insulin secretion, resulting in hyperglycaemia. Apart from insulin there are a number of hormones and cytokines that influence glucose homeostasis. Cytokines have traditionally been studied for their inflammatory effects, but have in recent years attracted increasing interest due to their effects on metabolism. IL-6 has a complex role in metabolism and has been shown to increase insulin sensitivity [1,2], but has been linked to insulin resistance [3]. Many of the cytokines and hormones that affect glucose homeostasis have been found to be secreted from brown adipose tissue (BAT). In studies of rodents rendered diabetic by the toxic substance streptozotocin, it has been shown that BAT is atrophied and that metabolic activity is reduced [6]. As the PET technique is fully quantifiable, it is possible to accurately assess the numerical glucose utilization per gram in different tissues, including BAT

Methods

Results

Conclusion