A cross-sectional, mono-centric pilot study of insulin resistance in enzyme replacement therapy patients with Gaucher type I without overweight

Uçar, Sema Kalkan; Çöker, Mahmut; Argın, Mehmet; Akman, Şenol; Kara, Sinan; Şimşek, Damla Gökşen; Darcan, Şükran

doi:10.1016/j.ymgme.2008.10.001

Cited by 15 publications

(9 citation statements)

References 7 publications

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“…A subsequent study that included larger numbers of Gaucher patients, some of whom were receiving enzyme replacement, showed that there was no increase in the prevalence of type II diabetes in Gaucher patients [97]. Interestingly, this study found that the number of these Gaucher patients that were overweight was less than in the general population, and further findings of Ucar et al [98] reported that insulin resistance in Gaucher disease was not related to overweight.…”

Section: Insulin Resistance and Gaucher Diseasementioning

confidence: 58%

Sphingolipids: the nexus between Gaucher disease and insulin resistance

Fuller

2010

Lipids Health Dis

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Sphingolipids constitute a diverse array of lipids in which fatty acids are linked through amide bonds to a long-chain base, and, structurally, they form the building blocks of eukaryotic membranes. Ceramide is the simplest and serves as a precursor for the synthesis of the three main types of complex sphingolipids; sphingomyelins, glycosphingolipids and gangliosides. Sphingolipids are no longer considered mere structural spectators, but bioactive molecules with functions beyond providing a mechanically stable and chemically resistant barrier to a diverse array of cellular processes. Although sphingolipids form a somewhat minor component of the total cellular lipid pool, their accumulation in certain cells forms the basis of many diseases. Human diseases caused by alterations in the metabolism of sphingolipids are conventionally inborn errors of degradation, the most common being Gaucher disease, in which the catabolism of glucosylceramide is defective and accumulates. Insulin resistance has been reported in patients with Gaucher disease and this article presents evidence that this is due to perturbations in the metabolism of sphingolipids. Ceramide and the more complex sphingolipids, the gangliosides, are constituents of specialised membrane microdomains termed lipid rafts. Lipid rafts play a role in facilitating and regulating lipid and protein interactions in cells, and their unique lipid composition enables them to carry out this role. The lipid composition of rafts is altered in cell models of Gaucher disease which may be responsible for impaired lipid and protein sorting observed in this disorder, and consequently pathology. Lipid rafts are also necessary for correct insulin signalling, and a perturbed lipid raft composition may impair insulin signalling. Unravelling common nodes of interaction between insulin resistance and Gaucher disease may lead to a better understanding of the biochemical mechanisms behind pathology.

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Section: Insulin Resistance and Gaucher Diseasementioning

confidence: 58%

Sphingolipids: the nexus between Gaucher disease and insulin resistance

Fuller

2010

Lipids Health Dis

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“…In addition, most of them included a small sample and were retrospective and non-controlled (Tables 1 and 2). According to their focus, the selected studies were grouped considering three aspects of the disease: 1) development of children and adolescents during pre- and post-ERT periods (n=17); 2) abnormalities in energy metabolism that remained during ERT (n=10); and 3) abnormalities in metabolic status arising after ERT (n=2, with one of them [9] also providing data related to the aspect of energy metabolism).…”

Section: Resultsmentioning

confidence: 99%

“…A study in Turkey evaluated insulin resistance in ERT patients with GD and without overweight (n=14), and showed that they had higher levels of fasting insulin, post-load glucose and insulin when compared to controls. Elevated insulin levels in GD type I patients were positively correlated with free fatty acid, triglyceride, and severity score [9]. …”

Section: Resultsmentioning

confidence: 99%

“…In addition, when compared to controls, the following changes were found in GD patients undergoing ERT: lower plasma adiponectin levels [25], higher levels of glucosylceramide in patients than in baseline controls [7,26], partial normalisation of glucosylceramide levels after 72 months of treatment [7], higher levels of post-load glucose, insulin, triglycerides, and fatty acids [9], and greater concentration of ganglioside GM3 in plasma [26,27]. These changes have indicated that, despite the efficacy of the treatment in solving some manifestations of the disease, it has not been as effective in treating certain metabolic changes.…”

Section: Discussionmentioning

confidence: 99%

“…According to a study conducted by Ucar et al [9], it is possible that patients with more severe GD have a reduction in insulin sensibility and a greater tendency to develop type 2 DM, even without being overweight. Additional studies with larger numbers of patients and other populations are needed to verify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

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Effects of imiglucerase on the growth and metabolism of Gaucher disease type I patients: a systematic review

et al. 2013

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BackgroundGaucher disease (GD) type I is the most common type of GD. Its main clinical manifestations are hepatosplenomegaly as well as bone and hematological abnormalities. The objective of the present study was to perform a literature review on the growth and metabolism of GD type I patients.MethodsWe searched Pubmed and Scielo.br databases with predetermined study limits: case series (n≥5), clinical trials, systematic reviews, and meta-analyses, and enzyme replacement therapy (ERT) with alglucerase or imiglucerase. The outcomes of interest were the following: growth and development, weight, height, malnutrition, overweight, obesity, basal metabolism, hypermetabolism, insulin resistance, and diabetes. A total of 175 articles were found, of which 28 met the inclusion criteria; these articles were grouped into three central themes: 1) growth of children and adolescents before and after ERT; 2) metabolic changes that remained during ERT; and 3) changes in metabolic status resulting from the treatment.Results and discussionThe articles included in the present literature review are very heterogeneous, which hinders the analysis of data. They indicated that GD patients usually show low weight and height before ERT, which are improved with treatment in children and adolescents. Studies evaluating the energy metabolism by indirect calorimetry have indicated that the disease is associated with hypermetabolism. In adults, some changes in energy metabolism remain on ERT, and alterations, such as insulin resistance, seem to be associated with the treatment. It is not clear which are the required doses of imiglucerase for obtaining an adequate cost-effective relation, as well as the advisable therapeutic measures to avoid possible long-term adverse effects related to ERT.ConclusionsERT tends to normalise the growth of children and adolescents with GD type I, it seems to cause a partial response in relation to some metabolic changes associated with the disease, and it can causes metabolic changes such as weight gain in adult patients. Therefore, additional research is necessary.

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Glycosphingolipids and Insulin Resistance

Aerts

Boot

Eijk

et al. 2011

Advances in Experimental Medicine and Biology

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Glycosphingolipids are structural membrane components, residing largely in the plasma membrane with their sugar-moieties exposed at the cell's surface. In recent times a crucial role for glycosphingolipids in insulin resistance has been proposed. A chronic state of insulin resistance is a rapidly increasing disease condition in Western and developing countries. It is considered to be the major underlying cause of the metabolic syndrome, a combination of metabolic abnormalities that increases the risk for an individual to develop Type 2 diabetes, obesity, cardiovascular disease, polycystic ovary syndrome and nonalcoholic fatty liver disease. As discussed in this chapter, the evidence for a direct regulatory interaction of glycosphingolipids with insulin signaling is still largely indirect. However, the recent finding in animal models that pharmacological reduction of glycosphingolipid biosynthesis ameliorates insulin resistance and prevents some manifestations of metabolic syndrome, supports the view that somehow glycosphingolipids act as critical regulators, Importantly, since reductions in glycosphingolipid biosynthesis have been found to be well tolerated, such approaches may have a therapeutic potential.

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A cross-sectional, mono-centric pilot study of insulin resistance in enzyme replacement therapy patients with Gaucher type I without overweight

Cited by 15 publications

References 7 publications

Sphingolipids: the nexus between Gaucher disease and insulin resistance

Sphingolipids: the nexus between Gaucher disease and insulin resistance

Effects of imiglucerase on the growth and metabolism of Gaucher disease type I patients: a systematic review

Glycosphingolipids and Insulin Resistance

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