Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A study of non-infective skin associations of diabetes mellitus was conducted on 100 consecutive outpatient diabetics over a 3-month period. 10 were insulin-dependent diabetics (IDDM), 24 insulin-requiring and 66 non-insulin dependent diabetics (NIDDM). A total skin evaluation was done for each patient with skin biopsy whenever appropriate. Twenty-three patients had diabetic dermopathy; the frequency of retinopathy in this group (39.1%) is significantly higher than that without diabetic dermopathy (6.9%) (p less than 0.001). There were 20 instances of cutaneous complications of therapy; 10 had insulin lipodystrophy (29.4% of 34 insulin users). Twelve patients, 8 of whom were overweight, had acanthosis nigricans. There were 6 Indians among them and all the patients had NIDDM. Eight had xanthelasma. Vitiligo occurred in 3.3% of those with NIDDM. Classical scleredema diabeticorum and cheiroarthropathy occurred in 2% of patients. One patient had atypical granuloma annulare. There was a higher incidence of xanthelasma in our study compared with studies done previously. Insulin lipodystrophy and acanthosis nigricans in the absence of classically described syndromes of insulin resistance seem to be fairly common phenomena and merit further investigation locally.
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PMID:Non-infective skin associations of diabetes mellitus. 322 40

Twenty-five patients with type I diabetes mellitus (8 women and 7 men) aged 19 to 54 with a disease duration of 3 to 19 years were treated by Russian semisynthetic short-acting human insulin mono-H. The daily dose varied from 24 to 44 U. The drug therapeutic efficacy was assessed from the terms of attainment of carbohydrate metabolism compensation, glycosylated hemoglobin level, and changes in daily insulin requirement. Clinical safety of the drug was assessed from changes in antiinsulin antibody level, incidence and severity of hypoglycemia, absence of lipodystrophy and other adverse reactions. The drug was found effective for the treatment of patients with type I diabetes. Its hypoglycemic effect was similar to that of actrapid, a porcine insulin. Fractionated insulin therapy resulted in the majority of patients in a reduction of glycosylated hemoglobin level, of daily requirement in insulin, and of antiinsulin antibody titer.
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PMID:[Use of domestic human insulin in patients with type I diabetes mellitus]. 841 19

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.
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PMID:Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes. 951 65

The course of HIV-infection has changed dramatically since the beginning of the epidemic. Opportunistic infections and AIDS-defining tumors are diagnosed less frequently since the introduction of antiretroviral therapy and the time of survival has increased. According to German-Austrian therapy guidelines highly active antiretroviral therapy (HAART) should be started on the onset of HIV-related symptoms and/or when the CD4 cell count is lower than 350/microl. Patients should be treated in specialized centres because of the complexity of HIV-infection and its therapy. For monitoring CD4 cell counts and viral load are determined. Reasons for therapeutic failure can be drug interactions, resistance or compliance problems. Although HIV-infection is often compared to insulin dependent diabetes mellitus psychological and social impact on HIV patients is still high. Increasing viral multi-drug resistance, long-term toxicity like lipodystrophy, osteoporosis and cardiovascular disease are only some problems HIV-infected patients are facing in the next years. In Germany 600 to 700 patients still die because of AIDS every year.
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PMID:[HIV-related symptoms]. 1711 97

Acquired reactive perforating collagenosis is a skin disorder characterised by the transepidermal elimination of altered collagen through the epidermis. Two distinct forms exist; an inherited form that present in childhood resulting from superficial trauma, scratching, insect bite, etc., and an acquired form that usually develops de novo in patients suffering from many chronic systemic and auto-immune diseases without any minor injury. Here a 36-year-old, insulin dependent diabetes mellitus patient with acquired variety of reactive perforating collagenosis and lipodystrophy at the sites of insulin injection sites is presented. Isotretinoin 0.1% cream was advised but with little improvement.
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PMID:Acquired reactive perforating collagenosis in an insulin dependent diabetes mellitus patient. 2046 88

Since its discovery, insulin has been used as highly specific and effective therapeutic protein to treat type 1 diabetes and later was associated to oral antidiabetic agents in the treatment of type 2 diabetes. Generally, insulin is administered parenterally. Although this route is successful, it still has several limitations, such as discomfort, pain, lipodystrophy at the injection sites and peripheral hyperinsulinemia, which may be the cause of side effects and some complications. Thus, alternative routes of administration have been developed, namely, those based on nanotechnologies. Nanoparticles, made of synthetic or natural materials, have been shown to successfully overcome the inherent barriers for insulin stability, degradation, and uptake across the gastrointestinal tract and other mucosal membranes. This review describes some of the many attempts made to develop alternative and more convenient routes for insulin delivery.
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PMID:Nanotechnology as a promising strategy for alternative routes of insulin delivery. 2244 31

The spectrum of adipose tissue diseases ranges from obesity to lipodystrophy, and is accompanied by insulin resistance syndrome, which promotes the occurrence of type 2 diabetes, dyslipidemia and cardiovascular complications. Lipodystrophy refers to a group of rare diseases characterized by the generalized or partial absence of adipose tissue, and occurs with or without hypertrophy of adipose tissue in other sites. They are classified as being familial or acquired, and generalized or partial. The genetically determined partial forms usually occur as Dunnigan syndrome, which is a type of laminopathy that can also manifest as muscle, cardiac, neuropathic or progeroid involvement. Gene mutations encoding for PPAR-gamma, Akt2, CIDEC, perilipin and the ZMPSTE 24 enzyme are much more rare. The genetically determined generalized forms are also very rare and are linked to mutations of seipin AGPAT2, FBN1, which is accompanied by Marfan syndrome, or of BANF1, which is characterized by a progeroid syndrome without insulin resistance and with early bone complications. Glycosylation disorders are sometimes involved. Some genetically determined forms have recently been found to be due to autoinflammatory syndromes linked to a proteasome anomaly (PSMB8). They result in a lipodystrophy syndrome that occurs secondarily with fever, dermatosis and panniculitis. Then there are forms that are considered to be acquired. They may be iatrogenic (protease inhibitors in HIV patients, glucocorticosteroids, insulin, graft-versus-host disease, etc.), related to an immune system disease (sequelae of dermatopolymyositis, autoimmune polyendocrine syndromes, particularly associated with type 1 diabetes, Barraquer-Simons and Lawrence syndromes), which are promoted by anomalies of the complement system. Finally, lipomatosis is currently classified as a painful form (adiposis dolorosa or Dercum's disease) or benign symmetric multiple form, also known as Launois-Bensaude syndrome or Madelung's disease, which are sometimes related to mitochondrial DNA mutations, but are usually promoted by alcohol. In addition to the medical management of metabolic syndrome and the sometimes surgical treatment of lipodystrophy, recombinant leptin provides hope for genetically determined lipodystrophy syndromes, whereas modifications in antiretroviral treatment and tesamorelin, a GHRH analog, is effective in the metabolic syndrome of HIV patients. Other therapeutic options will undoubtedly be developed, dependent on pathophysiological advances, which today tend to classify genetically determined lipodystrophy as being related to laminopathy or to lipid droplet disorders.
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PMID:How to diagnose a lipodystrophy syndrome. 2274 2

Metreleptin is an analogue of the human hormone leptin being developed by Amylin Pharmaceuticals (a subsidiary of Bristol-Myers Squibb) for the subcutaneous treatment of metabolic disorders including lipodystrophy. The compound is expected to improve insulin sensitivity, hypertriglyceridaemia and hyperglycaemia in patients with lipodystrophy who are unresponsive to conventional treatment. Metreleptin has been approved in Japan as a leptin therapy for the treatment of lipodystrophy. Amylin has also completed a submission for regulatory approval to the US FDA for metreleptin in the treatment of diabetes mellitus and/or hypertriglyceridaemia in patients with rare forms of lipodystrophy. Clinical development of the drug is also underway in the USA for the treatment of type 1 diabetes. Amgen was previously assessing the use of metreleptin as a treatment for amenorrhoea; however, it appears that development in this indication has been discontinued. This article summarizes the milestones in the development of metreleptin leading to this first approval for lipodystrophy.
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PMID:Metreleptin: first global approval. 2374 Apr 12

The ability of leptin to improve metabolic abnormalities in models of leptin deficiency, lipodystrophy, and even type 1 diabetes is of significant interest. However, the mechanism by which leptin mediates these effects remains ill-defined. Leptin was recently reported to regulate insulin-like growth factor-binding protein-2 (IGFBP2), and adenoviral overexpression of pharmacological levels of IGFBP2 ameliorates diabetic symptoms in many models of diabetes. We sought to determine the role of physiological levels of IGFBP2 in the glucoregulatory action of leptin. To investigate whether physiological levels of IGFBP2 are sufficient to mimic the action of leptin, we treated male ob/ob mice with low-dose IGFBP2 adenovirus (Ad-IGFBP2) or low-dose leptin. Despite similar levels of circulating IGFBP2, leptin but not Ad-IGFBP2 lowered body weight and plasma insulin and improved glucose and insulin tolerance. To elucidate the role of IGFBP2 in normal glucose homeostasis, we knocked down IGFBP2 in male C57BL/6 mice using small interfering RNA to determine whether this would recapitulate any aspect of the ob/ob phenotype. Despite successful IGFBP2 knockdown, body weight, blood glucose, and plasma insulin were unchanged. Finally, to determine whether IGFBP2 is required for the glucoregulatory actions of leptin, we prevented leptin-mediated increases in IGFBP2 in male ob/ob mice using RNA interference. Even though increases in IGFBP2 were blocked, the ability of leptin to decrease body weight, blood glucose, and plasma insulin levels were unaltered. In conclusion, physiological levels of IGFBP2 are neither sufficient to mimic nor required for the physiological action of leptin.
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PMID:IGFBP2 is neither sufficient nor necessary for the physiological actions of leptin on glucose homeostasis in male ob/ob mice. 2442 49

Lipodystrophy syndromes are frequently associated with marked degree of insulin resistance and lipoatrophic diabetes. Although acquired generalised lipodystrophy (AGL) has been known to be associated with various autoimmune disorders, type 1 diabetes mellitus (T1DM) is very rarely reported to occur with AGL. Combination of AGL and T1DM can lead to a totally different phenotype with very difficult-to-treat diabetes and progressive complications of both the conditions. We report a case of AGL with T1DM with poor diabetes control despite high doses of insulin, metformin and pioglitazone. Our case further progressed to develop complication of retroperitoneal fibrosis, not hitherto reported with AGL.
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PMID:Acquired generalised lipodystrophy and type 1 diabetes mellitus in a child: a rare and implacable association. 3007 64


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