Reduced brown adipose tissue‐associated skin temperature following cold stimulation in children and adolescents with type 1 diabetes

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.

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Effect of Liothyronine Treatment on Dermal Temperature and Activation of Brown Adipose Tissue in Female Hypothyroid Patients: A Randomized Crossover Study

Frontiers in Endocrinology ◽

10.3389/fendo.2021.785175 ◽

2021 ◽

Vol 12 ◽

Author(s):

Betty Ann Bjerkreim ◽

Sara Salehi Hammerstad ◽

Hanne Løvdal Gulseth ◽

Tore Julsrud Berg ◽

Sindre Lee-Ødegård ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Crossover Study ◽

Skin Temperature ◽

Secondary Outcome ◽

Clinical Trial Registration ◽

Cold Stimulation ◽

Cold Intolerance ◽

Brown Adipose ◽

Hypothyroid Patients

BackgroundThyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution.Materials and MethodsTo assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome.ResultsCold stimulated skin temperatures decreased less with LT3 vs. LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P<0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P<0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groupsConclusionLT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03627611

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Insulin-Independent Reversal of Type-1 Diabetes Following Transplantation of Adult Brown Adipose Tissue Supplemented With IGF-1

Transplantation Direct ◽

10.1097/txd.0000000000000945 ◽

2019 ◽

Vol 5 (11) ◽

pp. e500 ◽

Cited By ~ 2

Author(s):

Subhadra C. Gunawardana ◽

David W. Piston

Keyword(s):

Type 1 Diabetes ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose

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Insulin-independent reversal of type 1 diabetes in nonobese diabetic mice with brown adipose tissue transplant

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00570.2014 ◽

2015 ◽

Vol 308 (12) ◽

pp. E1043-E1055 ◽

Cited By ~ 45

Author(s):

Subhadra C. Gunawardana ◽

David W. Piston

Keyword(s):

Type 1 Diabetes ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Nod Mice ◽

Nonobese Diabetic ◽

Brown Adipose ◽

Igf I ◽

Onset Of Diabetes ◽

Nonobese Diabetic Mice

Traditional therapies for type 1 diabetes (T1D) involve insulin replacement or islet/pancreas transplantation and have numerous limitations. Our previous work demonstrated the ability of embryonic brown adipose tissue (BAT) transplants to establish normoglycemia without insulin in chemically induced models of insulin-deficient diabetes. The current study sought to extend the technique to an autoimmune-mediated T1D model and document the underlying mechanisms. In nonobese diabetic (NOD) mice, BAT transplants result in complete reversal of T1D associated with rapid and long-lasting euglycemia. In addition, BAT transplants placed prior to the onset of diabetes on NOD mice can prevent or significantly delay the onset of diabetes. As with streptozotocin (STZ)-diabetic models, euglycemia is independent of insulin and strongly correlates with decrease of inflammation and increase of adipokines. Plasma insulin-like growth factor-I (IGF-I) is the first hormone to increase following BAT transplants. Adipose tissue of transplant recipients consistently express IGF-I compared with little or no expression in controls, and plasma IGF-I levels show a direct negative correlation with glucose, glucagon, and inflammatory cytokines. Adipogenic and anti-inflammatory properties of IGF-I may stimulate regeneration of new healthy white adipose tissue, which in turn secretes hypoglycemic adipokines that substitute for insulin. IGF-I can also directly decrease blood glucose through activating insulin receptor. These data demonstrate the potential for insulin-independent reversal of autoimmune-induced T1D with BAT transplants and implicate IGF-I as a likely mediator in the resulting equilibrium.

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