Severe Lipoatrophy in a Patient With Type 2 Diabetes in Response to Human Insulin Analogs Glargine and Degludec: Possible Involvement of CD4 T Cell–Mediated Tissue Remodeling

Abstract

c A female patient age 69 years with .10-year history of type 2 diabetes (T2D), on a therapy of premixed aspart insulin, presented with poor glycemic control (HbA 1c 8.7%). c Change of therapy to three injections of short-acting aspart and once-daily glargine improved glycemic control but resulted in severe lipoatrophy at all sites of injection, a rare complication of insulin therapy almost exclusively associated with type 1 diabetes (T1D). c The patient had C-peptide levels within normal range and lacked autoantibodies against GAD, islet antigen 2 (IA-2), and tissue transglutaminase (tTg), excluding T1D. c Glargine injection was replaced by degludec, but this did not prevent formation of new indentures. c Histological analysis of tissue biopsies revealed strong tissue remodeling at affected sites including fibrosis, reduction of adipocyte size, and increased vascularization. c Immunohistochemical staining showed a strong influx of CD4 T cells in affected sites but no apparent signs of T cell-mediated cell death. c Flow cytometry of peripheral blood leukocytes did not show an overt effector cell profile of CD4 T cells, indicating that the response was mediated locally. c Our findings indicate that insulin-induced lipoatrophy in the context of T2D is distinct from that seen in T1D and appears to depend on CD4 T cell-mediated tissue remodeling.

The Identification of Key Genes and Biological Pathways in Polycystic Ovary Syndrome and its Complications by Next Generation Squancing (NGS) and Bioinformatics Analysis

“…This study indicated that enriched genes might play important role in PCOS. As previously reported, FOXP3 [446], TIMP4 [447], OAS3 [448], SOCS1 [128], CD74 [129], PLK1 [449], TGFB1 [450], RAPGEF1 [451], SERPINH1 [452], ATF5 [66], GATA6 [133], IGF2BP1 [453], IRX3 [454] [467], MGAT2 [468], LGR5 [469], SPINK1 [470], CYP19A1 [471], PLAC8 [90], CD36 [472], AQP5 [473], GIPR (gastric inhibitory polypeptide receptor) [474], ARG1 [475], SORL1 [476], CD4 [477], F11R [478], LEPR (leptin receptor) [479], CDH13 [480], AR (androgen receptor) [481], FOXO1 [102], MALT1 [482], PAM (peptidylglycine alpha-amidating monooxygenase) [483], B2M [484], TCF4 [485], CAV2 [486], HSBP1 [487], COLEC12 [488], ADRA2A [489], SLC38A4 [490], TM6SF2 [491], GLP2R [111], KLB (klotho beta) [492], NFAT5 [493], PON2 [494], ZMAT3 [495], DST (dystonin) [426], MGST3 [496], COQ2 [118], EPHX2 [497], C2 [181] and FAM3C [120] are altered expression in type 2 diabetes mellitus. Previous studies have shown that DRD4 [498], TIMP4 [499], SOCS1 [500], CD74 [501], TGFB1 [502], ACTG2 [503], ISG15 [504], HOXC8 [505], SNHG17 [506], IL1RL1 [507], BGN (biglycan) [508], SOD3 …”

Worsening of Glycemic Control in a Patient With Fulminant Type 1 Diabetes Receiving Sensor-Augmented Pump Therapy: A Case of Extensive Localized Lipoatrophy Requiring Attention in Relation to Cannula Insertion Sites

“…Although LL associated with insulin formulations occurs as a result of adipocyte atrophy, its mechanisms of onset are unclear (2,3). Putative mechanisms include influences of an immune response to insulin injections or to excipients of the injection solution, trauma from repeated local injections, inhibitory effects of macrophage-derived cytokines on adipocyte differentiation, and CD4 1 T cell-mediated tissue remodeling (4)(5)(6). Microscopic photographs of the skin depressions in this case showed evidence of infiltration of inflammatory cells (i.e., CD4 1 T cells and M2 macrophages) in parts of the vascular stroma, suggesting the likely involvement of CD4 1 T cell-mediated tissue remodeling in the onset of LL.…”