Lipoatrophic Diabetes in an Elderly Woman: Clinical Course and Serum Adipocytokine Concentrations

Abstract

Generalized lipodystrophy is a rare disorder of adipose tissue, whose etiology remains unknown. Pathophysiology of this disorder is characterized by generalized loss of body fat associated with an infrequent form of diabetes mellitus (lipoatrophic diabetes). Main features of this form of diabetes mellitus are the severe insulin resistance and the absence of ketoacidosis. Lipodystrophy can be congenital or acquired. In the acquired form, metabolic disturbances usually begin in the first years of life and the response to conventional treatment is very poor. Some alterations in serum adipocytokines have been described in this disease. We report the case of a 74-year-old woman with acquired generalized lipodystrophy who presented with low-normal serum concentrations of leptin, low adiponectin and resistin levels, and high serum levels of TNF alpha. Patient was initially treated with fenofibrate, metformin and high doses of subcutaneous insulin achieving an adequate metabolic control. During this period, serum adipocytokines were periodically measured. We comment on the different etiopathogenic mechanisms and the therapeutic modalities of this rare syndrome.

Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C

“…TNF-α is of particular interest, having been closely linked to obesity and the metabolic syndrome [20]. In contrast to our data, Hegele et al [2] found no change in plasma TNF-α in FPLD, although a recent case report of an individual with acquired idiopathic generalised lipodystrophy reported elevated plasma TNF-α in the presence of reduced adiponectin and leptin levels [10]. The relationship between adiponectin and the TNF-α system is of particular interest.…”

“…Thus, the low-adiponectin state may be the common defect in both obesity and lipodystrophy. However, increased plasma levels of various proinflammatory cytokines expressed by adipose tissue have also been observed in various groups of lipodystrophic subjects [7][8][9][10][11]. The aim of the present study was to investigate the interrelationships between the abnormalities of adiponectin and other adipokines, and to determine which defects are most closely predictive of the metabolic syndrome in a genetically and phenotypically well-characterised group of subjects with FPLD and unaffected controls.…”

A Case of Acquired Generalized Lipodystrophy with Cerebellar Degeneration and Type 2 Diabetes Mellitus

“…The plasma resistin is low in those patients, as reported by Iglesias and his colleagues [18], indicating that plasma resistin may not be related to the insulin resistance in patients with lipodystrophy. Tumor necrosis factor-α, a proinflammatory cytokine, also secreted from adipocytes, is reported to elevate plasma levels in a patient with AGL [18] and it is assumed that this might play a role in insulin resistance. The possible pathological mechanisms linking lipodystrophy and insulin resistance are summarized in Figure 2.…”

“…Serum leptin and adiponectin levels reflecting the amount of body fat are extremely low in patients with AGL and may be related to severe insulin resistance and its metabolic complications in lipodystrophies [11,13,30,31]. The plasma resistin is low in those patients, as reported by Iglesias and his colleagues [18], indicating that plasma resistin may not be related to the insulin resistance in patients with lipodystrophy. Tumor necrosis factor-α, a proinflammatory cytokine, also secreted from adipocytes, is reported to elevate plasma levels in a patient with AGL [18] and it is assumed that this might play a role in insulin resistance.…”

“…However, the present case may be an exceptional type of AGL, due to the accompanied neurological deficit as cerebellar degeneration. To date, AGL is a rare syndrome with less than 100 cases reported [9][10][11][12][13][14][15][16][17][18]. One case of familial lipodystrophy associated with neurodegeneration presented with spastic-ataxic gait and lower extremity paresthesiae at the age of 18 was observed before [19].…”