Lipoatrophy Induced by Subcutaneous Insulin Infusion: Ultrastructural Analysis and Gene Expression Profiling

Milan, Gabriella; Murano, Incoronata; Costa, Silvana Daher; Pianta, A; Tiengo, Cesare; Zulato, Elisabetta; Centobene, C.; Bruttomesso, Daniela; Cinti, Saverio; Vettor, Roberto

doi:10.1210/jc.2009-2773

Cited by 19 publications

(18 citation statements)

References 22 publications

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“…Adipocytes were shrunk and reduced in number, consistent with previous reports [3-5]. Milan et al [6] provided ultrastructural analyses on chronic lipoatrophies, having existed for eight months to six years (median 26 months) in three patients using Humalog™. They showed fat cell atrophy, deposition of amyloid, and numerous perivascular preadipocytes.…”

Section: Introductionsupporting

confidence: 85%

“…Various subcutaneously administered pharmaceuticals including hormone preparations [1-6,8-13,20,21] and vaccines [22] may be the cause of LIL. In cases of incipient insulin-induced LIL, the idiosyncratic trigger can obviously be turned off by systemic corticosteroid application, despite ongoing subcutaneous insulin administration.…”

Section: Discussionmentioning

confidence: 99%

“…They showed fat cell atrophy, deposition of amyloid, and numerous perivascular preadipocytes. Quantitative polymerase chain reaction revealed a reduction in adipocyte-specific messenger ribonucleic acid (mRNA) (perilipin, adiponectin, fatty acid-binding protein 4, peroxisome proliferator-activated receptor gamma 2), whereas mRNA of adipocyte enhancer-binding protein 1 was enhanced, and of leptin was reduced to zero [6]. There was no evidence of inflammation.…”

Section: Introductionmentioning

confidence: 99%

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Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

Chantelau¹,

Prätor²,

Prätor³

2014

J Med Case Reports

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IntroductionLocalized involutional lipoatrophy of subcutaneous adipose tissue may develop due to subcutaneous injection of pharmaceutical preparations. The pathogenesis of this adverse drug reaction is unknown. The progression of localized involutional lipoatrophy ceases and occasionally it resolves after withdrawing the inducing agent. In case of localized involutional lipoatrophy due to subcutaneous insulin therapy, low-dose systemic corticosteroids may be curative despite ongoing insulin administration.Case presentationWe report a recurrence of insulin-induced localized involutional lipoatrophy at the abdominal wall in a 57-year-old Caucasian woman with type-1 diabetes on continuous subcutaneous insulin infusion. The first episode of insulin-induced localized involutional lipoatrophy two years previously had been cured by oral prednisone. The recurrence was treated immediately with 10mg prednisone once daily for five months, and was cured thereafter. The insulin analog preparation (Humalog™) and the insulin pump equipment (Accu-Chek Spirit™) applied were the same during both episodes. Both episodes were preceded by a temporary disturbance of the immune balance (the first episode by vaccination, the second episode through shingles).ConclusionsThis case confirms that insulin-induced localized involutional lipoatrophy in type-1 diabetes can occur again, and can be cured by systemic corticosteroids. We suggest that temporary disturbance of the immune balance may trigger this transitory idiosyncratic reaction in a susceptible individual.

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Section: Introductionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

Chantelau¹,

Prätor²,

Prätor³

2014

J Med Case Reports

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“…This is suggestive of a hypersensitivity reaction, which has led to attempts to treat LA with the mast cell stabiliser sodium cromoglicate [25]. However, in their study of histological samples from 3 affected patients with T1D, Milan et al [3] argued against an inflammatory process in the development of LA. They proposed that LA results from adipocyte delipidation secondary to local insulin resistance, but their analysis may have been limited by only sourcing samples from areas of established LA and not, for example, from the edges between normal and LA tissue [6].…”

Section: Discussionmentioning

confidence: 99%

“…An underlying immunological mechanism was originally proposed by Paley [1] in 1953. Peters and Winkelmann [2] suggested that transitory lymphocyte-mediated panniculitis is the primary lesion that progresses to LA, which has recently been called into question [3]. …”

Section: Introductionmentioning

confidence: 99%

Lipoatrophy Is Associated with an Increased Risk of Hashimoto's Thyroiditis and Coeliac Disease in Female Patients with Type 1 Diabetes

et al. 2013

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Background/Aims: Lipoatrophy (LA) is a rare, possibly under-recognised side effect of insulin treatment of unclear aetiology. The aim of this study was to describe the characteristics of patients with type 1 diabetes (T1D) who have LA and to explore the relationship between LA and other autoimmune diseases based on the hypothesis that additional autoimmune phenomena are more prevalent in T1D patients with LA. Methods: This was a cross-sectional observational study of T1D patients with LA in comparison to T1D patients without LA who are registered with the Diabetes Patienten-Verlaufsdokumentationssystem database of 241,650 patients in Germany and Austria. Results: Hashimoto's thyroiditis and coeliac disease were more prevalent in patients with LA (p < 0.001 for both). LA was associated with an increased risk of Hashimoto's thyroiditis and coeliac disease in female patients [odds ratio (OR) 2.5, p = 0.003, and OR 3.1, p = 0.02, respectively]. This relationship persisted after adjustment for current age, duration of diabetes and calendar year of treatment (OR 2.7, p = 0.002, and OR 3.5, p = 0.01, respectively). Conclusion: These findings support the hypothesis that an immune complex-mediated inflammatory process may be important in the development of LA.

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Adipose Organ Development and Remodeling

Cinti

2018

Comprehensive Physiology

149

121

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During the last decades, research on adipose tissues has spread in parallel with the extension of obesity. Several observations converged on the idea that adipose tissues are organized in a large organ with endocrine and plastic properties. Two parenchymal components: white (WATs) and brown adipose tissues (BATs) are contained in subcutaneous and visceral compartments. Although both have endocrine properties, their function differs: WAT store lipids to allow intervals between meals, BAT burns lipids for thermogenesis. In spite of these opposite functions, they share the ability for reciprocal reversible transdifferentiation to tackle special physiologic needs. Thus, chronic need for thermogenesis induces browning and chronic positive energy balance induce whitening. Lineage tracing and data from explant studies strongly suggest other remodeling properties of this organ. During pregnancy and lactation breast WAT transdifferentiates into milk-secreting glands, composed by cells with abundant cytoplasmic lipids (pink adipocytes) and in the postlactation period pink adipocytes transdifferentiate back into WAT and BAT. The plastic properties of mature adipocytes are supported also by a liposecretion process in vitro where adult cell in culture transdifferentiate to differentiated fibroblast-like elements able to give rise to different phenotypes (rainbow adipocytes). In addition, the inflammasome system is activated in stressed adipocytes from obese adipose tissue. These adipocytes die and debris are reabsorbed by macrophages inducing a chronic low-grade inflammation, potentially contributing to insulin resistance and T2 diabetes. Thus, the plastic properties of this organ could open new therapeutic perspectives in the obesity-related metabolic disease and in breast pathologies. © 2018 American Physiological Society. Compr Physiol 8:1357-1431, 2018.

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Lipoatrophy Induced by Subcutaneous Insulin Infusion: Ultrastructural Analysis and Gene Expression Profiling

Cited by 19 publications

References 22 publications

Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

Insulin-induced localized lipoatrophy preceded by shingles (herpes zoster): a case report

Lipoatrophy Is Associated with an Increased Risk of Hashimoto's Thyroiditis and Coeliac Disease in Female Patients with Type 1 Diabetes

Adipose Organ Development and Remodeling

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