Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.
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PMID:Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications. 1693 9

Management of diabetes mellitus can be responsible for cutaneous adverse events. For example, lipoatrophy or lipohypertrophy can develop at the site of insulin injections. Lipohypertrophy remains a frequent complication of insulin therapy irrespective of the insulin source and mode of administration. Lipoatrophy at insulin injection sites is considered to be an immune complex-mediated inflammatory lesion; however, it has become a rare event since the advent of human insulin. Nowadays, continuous subcutaneous insulin infusion (CSII) using a portable pump and/or injections of insulin analogs with an altered amino acid sequence compared with native insulin may cause lipodystrophy in diabetic patients. Some case reports describe the recovery of lipoatrophy following the use of CSII and/or short-acting insulin analogs. Conversely, exceptional cases of lipoatrophy have occurred in patients receiving lispro insulin analog via CSII. Lipodystrophy reactions remain a potential problem when managing diabetic patients with new insulin therapy technologies.
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PMID:Lipodystrophy reactions to insulin: effects of continuous insulin infusion and new insulin analogs. 1729 3

Primary lipodystrophies represent a heterogeneous group of very rare diseases with a prevalence of less than 1 case for 100.000, inherited or acquired, caracterized by a loss of body fat either generalized or localized (lipoatrophy). In some forms, lipoatrophy is associated with a selective hypertrophy of other fat depots. Clinical signs of insulin resistance are often present: acanthosis nigricans, signs of hyperandrogenism. All lipodystrophies are associated with dysmetabolic alterations with insulin resistance, altered glucose tolerance or diabetes and hypertriglyceridemia leading to a risk of acute pancreatitis. Chronic complications are those resulting from diabetes involving the retina, kidney and nerves, cardiovascular complications and steatotic liver lesions that could result in cirrhosis. Genetic forms of generalized lipodystrophy (or Berardinelli-Seip syndrome) result, in most cases, from recessive mutations in one of two genes: either BSCL2 coding seipin or BSCL1 coding AGPAT2, an acyl-transferase involved in triglyceride synthesis. Acquired generalized lipodystrophy (Lawrence syndrome) is of unknown origin but is sometimes associated with signs of autoimmunity. Partial lipodystrophies can be familial with dominant transmission. Heterozygous mutations have been identified in the LMNA gene encoding nuclear lamin A/C belonging to the nuclear lamina, or in PPARG encoding the adipogenic transcription factor PPARgamma. Some less typical lipodystrophies, associated with signs of premature aging, have been linked to mutations in LMNA or in the ZMPSTE24 gene encoding the protease responsible for the maturation of prelamin A into lamin A. Acquired partial lipodystrophy (Barraquer-Simons syndrome) is characterized by cephalothoracic fat loss. Its aetiology is unknown but mutations in LMNB2, encoding the lamina protein lamin B2, could represent susceptibility factors. Highly active antiretroviral treatments for HIV infection are currently the most frequent cause of acquired secondary lipodystrophic syndromes. The genetic diagnosis is performed in specialized laboratories and, in the most severe forms, antenatal diagnosis could be proposed. Treatment of diabetes, dyslipidemia and complications involves the classical intervention strategies. Insulino-sensitizing drugs are useful. Therapeutic trials with recombinant human leptin in patients with very low leptin levels reported good results with respect to the metabolic and liver alterations. The prognosis is linked to the precocity and severity of the diabetic, cardiovascular and liver complications.
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PMID:[Primary lipodystrophies]. 1732 32

Most patients with acanthosis nigricans have either clinical or subclinical insulin resistance. We undertook a study to estimate the insulin sensitivity of a group of patients referred from the dermatologist with biopsy proven acanthosis nigricans. Thirty-six patients were evaluated in the Endocrinology clinic. Plasma glucose and serum Insulin levels were estimated after a 75 gms oral glucose load (OGTT). An intravenous Insulin Tolerance Test (ITT) was performed with measurement of Glucose Disposal Rate (GDR). There were 28 females and 8 males (M:F--3.5:1; mean age 26.3+/-1.7 years) in the study. 25/36 patients were morbidly obese (BMI--36.0 +/- 1.2 Kg/m2) with an abnormal body fat distribution (WH ratio--0.9 +/ - 0.02). One patient had generalized lipoatrophy. 16/36 patients with acanthosis nigricans had IGT or overt diabetes and all had highly significant hyperinsulinemia (AUCI = 20825 +/ 1287.7 vs. 6340.0 +/- 984.2 mIU/ml/hr in controls, p < 0.0005). The GDR in patients with acanthosis nigricans was reduced (-0.66 +/- 0.07) compared to controls (-0.39 +/- 0.08; p < 0.01). There was a significant positive correlation between indices of adiposity and insulin resistance in subjects with impaired tolerance.
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PMID:Acanthosis nigricans: a dermatologic marker of metabolic disease. 1765 80

Lipoatrophy (LA) is a rare complication of insulin treatment in type 1 diabetes mellitus. The pathogenesis of insulin-induced LA is still unknown. Many theories suggest immunological reactions. We report a 4-yr-old Saudi girl with LA probably induced by lispro insulin. A review of the literature on the clinical features, pathophysiology, differential diagnosis, and treatment is briefly discussed.
Pediatr Diabetes 2007 Dec
PMID:Lispro insulin-induced lipoatrophy: a new case. 1803 67

Antiretroviral (ARV) medications have been in clinical use for 20 years in the treatment of HIV and our knowledge about the safety of these medicines continues to grow. The potential side effects of ARVs can be either short term, such as hypersensitivity reactions, drug-induced hepatitis, anemia and lactic acidosis, or long term, including dyslipidemia, cardiovascular disease, lipoatrophy, lipohypertrophy and diabetes. In general, the safety profile of ARVs is improving as new combinations of medicines and newer medicines are introduced into clinical practice. However, it is crucial that vigilance be maintained in monitoring for side effects, particularly in resource-limited settings.
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PMID:The safety of antiretroviral drugs. 1817 9

Lipoatrophy is a rare cutaneous side-effect that can develop at the site of insulin injection. Since the introduction of human recombinant insulin the number of cases has decreased although cases have been reported in association with the use of rapid acting insulin analogues and continuous subcutaneous insulin infusion (CSII), recently one case has been reported with the use of insulin glargine. Insulin-induced lipoatrophy is a subcutaneous fat atrophy at the sites of injection which is relevant not only because of the cosmetic problem, but also because of the variability of absorption it causes in the site of injection. This report describes a patient with a type 1 diabetes mellitus who develops a lipoatrophy induced by insulin detemir. To our understanding this is one of the first reported cases of lipoatrophy induced by insulin detemir.
Diabetes Res Clin Pract 2008 Apr
PMID:A case of lipoatrophy with insulin detemir. 1828 Nov 21

A case of a 32-year-old woman with type 1 diabetes diagnosed 1.5 year before presention. The patient was referred to the diabetology department due to decompensation of diabetes and excessive hypodermic atrophy of both thighs. Early symptoms of lipoatrophy appeared after 1.5-2 months of insulin glargine use, in spite of frequently changed hypodermic needles and injection sites on both thighs. Simultaneously, deterioration of diabetes compensation was observed (hyperglycaemia between meals and in the morning), which was corrected by the patient with extra injections of a short acting analogue. Additional examinations confirmed type 1 diabetes (C-peptide <0.01 ng/ml) with concomitant hypothyroidism in the course oh Hashimoto disease. After change of insulin (Insulatard twice daily, Novo Rapid with meals) and injection site (administration to hypodermic tissues of arms and abdomen was started), diabetes compensation was achieved. At follow-up visit after 12 months, diabetes was still under control - HbA1c 6.8%. Moreover, progress of lipoatrophy is not observed.
Pediatr Endocrinol Diabetes Metab 2008
PMID:[Lipoatrophy after use of long acting insulin glargine analogue in a 32-year-old patient with type 1 diabetes]. 1857 50

Targeted ablation of the novel flavoheme reductase Ncb5or knock-out (KO) results in progressive loss of pancreatic beta-cells and white adipose tissue over time. Lipoatrophy persisted in KO animals in which the confounding metabolic effects of diabetes were eliminated by islet transplantation (transplanted knockout (TKO)). Lipid profiles in livers prepared from TKO animals were markedly deficient in triglycerides and diacylglycerides. Despite enhanced expression of stearoyl-Co-A desaturase-1, levels of palmitoleic and oleic acids (Delta9 fatty acid desaturation) were decreased in TKO relative to wild type controls. Treatment of KO hepatocytes with palmitic acid reduced cell viability and increased apoptosis, a response blunted by co-incubation with oleic acid. The results presented here support the hypothesis that Ncb5or supplies electrons for fatty acid desaturation, offer new insight into the regulation of a crucial step in fatty acid biosynthesis, and provide a plausible explanation for both the diabetic and the lipoatrophic phenotype in Ncb5or(-/-) mice.
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PMID:Loss of Ncb5or results in impaired fatty acid desaturation, lipoatrophy, and diabetes. 1868 84

Subcutaneous atrophy and central fat accumulation are common among HIV-infected patients receiving highly active antiretroviral therapy, and may be accompanied by dyslipidemia and insulin resistance. These fat changes, although commonly referred to together as lipodystrophy, are best considered as separate disorders, with distinct pathogeneses and treatment approaches. These morphological and metabolic abnormalities first appeared after introduction of protease inhibitors more than 10 yr ago, but research has demonstrated that their pathogenesis is multifactorial, with contributions from other antiretroviral medications, patient-related factors, and HIV itself. Switching to a less toxic highly active antiretroviral therapy regimen has shown partial effectiveness for the management of fat atrophy and lipid abnormalities. Lifestyle modification or surgical approaches are the treatment of choice for lipohypertrophy, although novel therapies targeting the GH axis show promise. HIV-related dyslipidemia may be difficult to treat, and can be complicated by drug-drug interactions between some lipid-lowering medications and antiretroviral medications. Treatment of diabetes in HIV-infected patients should generally follow established guidelines, but thiazolidinediones, rather than metformin, may be considered first-line treatment in a patient with lipoatrophy, given their potential to increase sc fat. The contribution of body fat changes and metabolic abnormalities to cardiovascular risk and the changing risk profiles of newer antiretroviral regimens are under intense investigation.
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PMID:Approach to the human immunodeficiency virus-infected patient with lipodystrophy. 1868 15


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