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      Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control

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          Abstract

          Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear.

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          Reduced Adipose Tissue Oxygenation in Human Obesity

          Magdalena Pasarica, Olga Sereda, Leanne Redman … (2009)
          OBJECTIVE— Based on rodent studies, we examined the hypothesis that increased adipose tissue (AT) mass in obesity without an adequate support of vascularization might lead to hypoxia, macrophage infiltration, and inflammation. RESEARCH DESIGN AND METHODS— Oxygen partial pressure (AT pO2) and AT temperature in abdominal AT (9 lean and 12 overweight/obese men and women) was measured by direct insertion of a polarographic Clark electrode. Body composition was measured by dual-energy X-ray absorptiometry, and insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Abdominal subcutaneous tissue was used for staining, quantitative RT-PCR, and chemokine secretion assay. RESULTS— AT pO2 was lower in overweight/obese subjects than lean subjects (47 ± 10.6 vs. 55 ± 9.1 mmHg); however, this level of pO2 did not activate the classic hypoxia targets (pyruvate dehydrogenase kinase and vascular endothelial growth factor [VEGF]). AT pO2 was negatively correlated with percent body fat (R = −0.50, P < 0.05). Compared with lean subjects, overweight/obese subjects had 44% lower capillary density and 58% lower VEGF, suggesting AT rarefaction (capillary drop out). This might be due to lower peroxisome proliferator–activated receptor γ1 and higher collagen VI mRNA expression, which correlated with AT pO2 (P < 0.05). Of clinical importance, AT pO2 negatively correlated with CD68 mRNA and macrophage inflammatory protein 1α secretion (R = −0.58, R = −0.79, P < 0.05), suggesting that lower AT pO2 could drive AT inflammation in obesity. CONCLUSIONS— Adipose tissue rarefaction might lie upstream of both low AT pO2 and inflammation in obesity. These results suggest novel approaches to treat the dysfunctional AT found in obesity.
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            Adipokines: inflammation and the pleiotropic role of white adipose tissue.

            Paul Trayhurn, I. Wood (2004)
            White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.
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              Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes.

              M. Blanco, M. T. Hernández Aguilar, K W Strauss … (2013)
              Our objective was to assess the frequency of lipohypertrophy (LH) and its relationship to site rotation, needle reuse, glucose variability, hypoglycaemia and use of insulin.
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                Author and article information

                Journal
                Title: Diabetes Care
                Abbreviated Title: Dia Care
                Publisher: American Diabetes Association
                ISSN (Print): 0149-5992
                ISSN (Electronic): 1935-5548
                Publication date Created: August 23 2016
                Publication date Created: September 2016
                Publication date (Print): September 2016
                Publication date (Electronic): July 13 2016
                Volume: 39
                Issue: 9
                Pages: 1486-1492
                Article
                DOI: 10.2337/dc16-0610
                PubMed ID: 27411698
                SO-VID: 4126bb3d-cae3-40a1-924f-8956aef07975
                Copyright © © 2016
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