Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors analyzed the effects of obesity/non-obesity in 162 epidoses of severe metabolic disturbances. Ketoacidosis and hypoglycaemics comas were more frequent in the non-obese group of diabetics, who were often insulin treated; whereas hyperosmolar coma and lactic acidosis were frequent in the obese group of diabetics, usually not treated with insulin. In the obese group both advanced age as well as a higher frequency of degenerative complications impaired the prognosis of these metabolic accidents. However the mortality rate was not significantly different in the two groups of patients. Despite the importance of the weight balance in the natural history of diabetes mellitus, it did not seem to influence the clinical aspects nor did it modify the therapeutic management of the major metabolic disturbances which occur in diabetes.
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PMID:[Major metabolic disturbances occur in diabetic patients whether they are obese or not (author's transl)]. 11 Dec 20

Two main classes of oral hypoglycaemic drugs, the sulphonylureas and the biguanides, are currently used in the therapy of type II, non-insulin-dependent diabetes mellitus (NIDDM). The basic pharmacokinetic properties of these agents are discussed with a view to efficient and safe treatment. Both first- and second-generation sulphonylureas are rapidly absorbed from the gastrointestinal tract. In the plasma compartment, these drugs are strongly bound to serum proteins. All sulphonylureas are metabolised in the liver, and the metabolites and the parent drugs are eliminated mainly in the urine, but also (second-generation derivatives) in the faces. Rapid- and short-acting sulphonylureas may improve early insulin release and promote better postprandial glucose control. Long-acting derivatives may ensure better control of overnight glycaemia. The elderly are at risk of developing severe sulphonylurea-induced hypoglycaemia, and in this population the agent chosen should have a short or intermediate duration of action and no active metabolites. Caution is needed when prescribing any sulphonylurea in patients receiving drugs known to affect sulphonylurea action, and in those with impaired liver and/or kidney function. The bioavailability of the biguanides ranges from 40 to 60%. Binding to plasma proteins is absent or very low. Metformin and buformin are not metabolised and are excreted in the urine; phenformin undergoes hepatic hydroxylation and is excreted in both urine and faeces. Metformin is the only agent of this class currently recommended for clinical use. The main indications of metformin treatment are NIDDM associated with obesity and/or hyperlipidaemia, and in combination with sulphonylurea both as primary treatment and when secondary failure occurs with sulphonylurea alone. Lactic acidosis may develop in patients receiving therapy with biguanides, especially in the presence of a preexisting contraindication to their use.
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PMID:Pharmacokinetic optimisation of oral hypoglycaemic therapy. 176 Sep 2

Metformin, one of the biguanides, is an oral hypoglycemic agent which acts primarily by decreasing hepatic glucose output and by increasing peripheral glucose disposal, therefore it has different hypoglycemic mechanism from that of sulfonylureas. The hypoglycemic effects of metformin are observed not only in obese NIDDM patients, but also in non-obese NIDDM patients. Moreover, addition of metformin improves glycemic control in patients with suboptimal glycemic control while taking maximum sulfonylurea therapy. Therefore, it is complementary to sulfonylurea therapy and represents a useful additional drug for the treatment, irrespective of obesity. The rare but serious condition of lactic acidosis should be kept in mind as a potential side effect, however, if metformin is avoided in patients with contraindications, the medication is very safe.
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PMID:[Therapeutic utility of biguanides in the treatment of NIDDM]. 1019 50

Steatosis or fatty liver in individuals with human immunodeficiency virus (HIV) may result from HIV itself, the use of nucleoside analogues, concurrent infection with hepatitis B or C, alcohol use, diabetes mellitus, obesity, or combinations of these factors. Nucleoside analogues have been the focus of increasing concern, because several fatal cases of severe macrosteatosis, lactic acidosis, and hepatomegaly have been linked to the use of nucleoside analogues. Other classes of antiretroviral drugs, as well as opportunistic infections, can also cause hepatic injury without steatosis. The additive effect of these different risk factors, especially in the presence of underlying hepatic steatosis, likely contributes to the increased prevalence of hepatic abnormalities among HIV-infected individuals. The conditions under which some patients rapidly progress to hepatic failure and/or cirrhosis need to be defined. This is a US government work. There are no restrictions on its use.
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PMID:The fatty liver in AIDS. 1194 34

MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly and Obesity) is an X-linked disorder characterised by mental retardation, epileptic seizures, hypogenitalism, microcephaly and obesity. It was recently assigned to the locus Xp21.1-p22.13. We describe a child with MEHMO and lactic acidosis whose muscle biopsy revealed markedly reduced activities of complexes 1,3 and 4 of the mitochondrial electron transport chain. Histological staining showed mitochondrial proliferation and lipid storage. Electron microscopy revealed abnormal and enlarged mitochondria with concentric cristae and electron dense bodies. This is the first identification of MEHMO as a mitochondrial disorder and one of the very few X-linked mitochondrial syndromes.
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PMID:MEHMO (Mental retardation, Epileptic seizures, Hypogenitalism, Microcephaly, Obesity): a new X-linked mitochondrial disorder. 1203 29

Lactic acidosis has been reported as a rare but potentially fatal complication of anti-retroviral therapy in HIV-infected patients, mostly with nucleoside analogues. Two cases of lactic acidosis with a favorable prognosis are here reported. So far, no distinct risk factors associated with the development of lactic acidosis have been identified which were associated with the use of anti-retroviral agents, apart from female sex, obesity, and the prolonged use of necleoside reverse transcriptase inhibitors. Currently, there is no specific treatment for this condition, apart from drug discontinuation and hydro-electrolytic support. Several therapies based upon the pathophysiology of this entity have been tested, but none of them has been validated so far.
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PMID:[Symptomatic hyperlactatemia associated with the use of antiretroviral agents]. 1236 52

Mitochondria are fundamental for oxidative energy production and impairment of their functionality can lead to reduced ATP synthesis and contribute to initiation of apoptosis. Endocrine tissues critically rely on oxidative phosphorylation so that mitochondrial abnormalities may either be causes or consequences of diminished hormone production or action. Abnormalities typical for diseases caused by mitochondrial DNA mutations such as Kearns-Sayre syndrome or mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome are also seen in certain endocrine diseases. Lack or excess of thyroid hormones, major ubiquitous regulators of mitochondrial content and activity, cause muscular abnormalities and multisystem disorders. Mitochondria are a further prerequisite for steroidogenesis as well as insulin secretion and action. Recent studies showed that reduced mitochondrial ATP synthesis in skeletal muscle is a feature of certain hereditary and acquired forms of insulin resistance and diabetes mellitus. Finally, ageing is not only accompanied by various degrees of hormonal deficiency and insulin resistance but is also associated with a progressive decline of mitochondrial number and function. Future research is needed to examine whether mitochondrial abnormalities are the cause or consequence of ageing and frequent metabolic diseases such as obesity and type 2 diabetes mellitus, and to address mitochondria as a target for novel therapeutic regimes.
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PMID:ESCI Award 2006. Mitochondrial function and endocrine diseases. 1737 58

Maternally inherited diabetes with deafness (MIDD) is a rare, monogenic form of diabetes mellitus caused by mutations in the mitochondrial genome, the most frequent being the A3243G substitution of the tRNA(Leu) gene. We screened 520 individuals with type 2 diabetes mellitus and 45 probands from families with a clinical picture of maturity onset diabetes of the young (MODY) using restriction fragment length polymorphism. One carrier of the mutation being investigated was found in a proband from a MODY family. The patient was a 20 year-old woman, diagnosed at the age of 16 years as having type 1 diabetes mellitus. On entry to the study, she was treated by a multiple daily injection regimen (MDI) with regular human insulin and human NPH insulin. Typical extra-pancreatic symptoms of MIDD were present, such as macular pattern dystrophy and mild bilateral sensory hearing loss. Additionally, the patient presented abdominal obesity (BMI 32.0), an uncommon feature in monogenic insulin secretion defects, including MIDD. To facilitate weight loss, the diabetes treatment was modified. Since metformin treatment is considered to be contraindicated in MIDD because of the increased risk of lactic acidosis, we used insulin analogues (aspart and detemir) in an MDI regimen and hypocaloric diet. This resulted in a 6.3 kg weight reduction (BMI 27.4) and normalization of HbA1c level (from 7.2 to 6.1 %) during a three-month follow-up. On the basis of this case, we suggest that an MDI regimen with insulin analogues may be a preferred therapeutic option in some rare clinical situations, such as MIDD associated with obesity.
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PMID:Maternally inherited diabetes with deafness and obesity: body weight reduction response to treatment with insulin analogues. 1748 45

Many patients taking atypical antipsychotic drugs will experience weight gain. Evidence suggests that long-term treatment with these agents decreases glucose effectiveness, alters satiety signals, creates hormonal resistance to satiety control, and may have a direct effect on hypothalamic appetite centers. The serotonin(2c-) and histamine(1)-receptor antagonism of atypical antipsychotics may also lead to weight gain. Several nonpharmacologic and pharmacologic methods have been used to address this adverse effect, with varying success. Metformin is an antidiabetic drug that has been shown to cause weight loss in patients with diabetes mellitus, as well as in some individuals without diabetes. To evaluate whether metformin can decrease weight gain induced by atypical antipsychotics in patients without diabetes, we conducted a literature search using the MEDLINE database (1970-October 2008) and clinicaltrials.gov Web site for relevant trials. Overall, 14 articles were identified for inclusion; review articles, case reports, and open-label studies were excluded. Thus, eight double-blind, placebo-controlled studies were reviewed; both pediatric and adult trials were included. Metformin has several advantages, including ease of use and a favorable safety profile. Although lactic acidosis was not reported in any of the studies reviewed, this potentially rare but severe adverse effect must be considered when prescribing this agent. Limited data suggest that metformin may attenuate weight gain in both adult and adolescent patients taking atypical antipsychotics. However, most of the trials included foreign populations, were only 12-16 weeks in duration, and the dosage of metformin may not have been adequately titrated. Although the study results do not provide clear substantial evidence that metformin, as an adjuvant to atypical antipsychotic use, will decrease weight gain and improve metabolic effects, they are encouraging. Additional studies of longer duration that include behavioral therapy and special diets should be conducted in patients from the United States. Currently, the drug is being used as a secondary or tertiary intervention, and its use may be considered in patients with a personal and/or family history of obesity or metabolic dysfunction, and in subjects who have rapid weight gain early in antipsychotic treatment.
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PMID:Management of atypical antipsychotic drug-induced weight gain: focus on metformin. 1947 23

Type Ia Glycogen storage disease is an autosomal recessive hepatic metabolic disease due to a lack of glucose-6-phosphatase (G-6-Pase) activity presenting with growth retardation, lactic acidosis, fasting hypoglycemia with hypoinsulinemia, hyperuricemia, hepatomegaly, and hepatic adenoma with a risk of malignancy. The gene that encodes G-6-Pase was mapped to 17q21. There are some genotype-phenotype correlations. We report a case with delF327 mutation which is devoid of G-6-Pase activity; however clinical presentation in this case differs somewhat. Although correction of hypoglycemia and lactic acidosis with nocturnal intragastric feeding and uncooked starch therapy improves growth failure, mean height of the patients is often less than the target. Normal height and obesity in this case with hepatic steatosis and low hepatic glycogen storage requires clinical reevaluation since there are some overlapping phenotypes between type Ia GSD and metabolic syndrome. The phenomenon may be related to insulin resistance as a consequence of early aggressive nutrition therapy with frequent low glycemic index meals.
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PMID:Obesity and reversed growth retardation in a child with type Ia glycogen storage disease. 2066 51


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