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Query: UMLS:C0497406 (overweight)
 26,365 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Weight reduction in non-insulin dependent diabetes mellitus (NIDDM) patients improves metabolic control, reduces cardiovascular risk factors, has blood pressure lowering effects and improves the well-being of the patient. This paper describes the role of very low calorie diets (VLCD), exercise, beta-adrenergic drugs and serotoninergic agents in the treatment of overweight in NIDDM. VLCD reduce body weight and improve glucose metabolism. Physical exercise programmes in addition to dietary restriction substantially contribute to weight loss and metabolic control in NIDDM. New specific beta-adrenergic agents, exhibiting virtually no beta 1 or beta 2 activity, increase energy expenditure and weight loss probably by enhancement of the basal metabolic rate. The target tissue in humans of this beta-adrenergic effect is as yet unknown. These drugs seem to enhance weight loss when used in combination with (very) low calorie diets compared to dietary restriction alone. Serotoninergic drugs reduce body weight by decreasing appetite, in particular for carbohydrates. Furthermore these drugs seem to improve insulin receptor sensitivity.
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PMID:Very low calorie diets and recently developed anti-obesity drugs for treating overweight in non-insulin dependent diabetics. 136 97

Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes.
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PMID:Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo. 221 48

The frequencies of restriction-fragment-length polymorphism (RFLP) alleles as well as RFLP haplotypes at six genetic loci responsible for carbohydrate and lipid metabolism [insulin/insulin-like growth factor II complex, insulin receptor (INSR), HepG2/erythrocyte-type glucose transporter, apolipoprotein A-II, apolipoprotein B (APOB), and the apolipoprotein A-I/C-III/A-IV cluster (APOA1/C3/A4)] were compared between nondiabetic and diabetic Chinese Americans. The disease-association data suggest that genetic variation at the INSR, APOB, and APOA1/C3/A4 loci contributes to the development of non-insulin-dependent diabetes mellitus (NIDDM). The analysis of the INSR locus revealed "protective" haplotypes, and it may be possible to use two of the INSR haplotypes as genetic markers to identify individuals having a very low probability of developing NIDDM regardless of the presence of other genes conferring susceptibility to this disorder. The APOB and APOA1/C3/A4 loci appear to contribute to the development of NIDDM in individuals who are of lean/normal weight and overweight, respectively. The APOA1/C3/A4 locus may account for approximately 8% of the difference between baseline and total possible risk of NIDDM in overweight individuals.
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PMID:Insulin-receptor and apolipoprotein genes contribute to development of NIDDM in Chinese Americans. 256 31

The tyrosine kinase activity of the insulin receptor was investigated in skeletal muscle biopsies from insulin-resistant males with obesity or with Type 2 (non-insulin-dependent) diabetic males who were lean or overweight. The kinase activity of the receptor from all three groups of insulin-resistant subjects was 40% less when compared to the activity of lean control subjects. This alteration was present in the absence of changes in the level of the insulin receptor on its insulin binding characteristics. We conclude that the tyrosine kinase activity of the skeletal muscle insulin receptor is defective in obesity and Type 2 diabetes, and that this alteration contributes to the insulin-resistant characteristics of both disorders.
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PMID:Defective insulin receptor tyrosine kinase in human skeletal muscle in obesity and type 2 (non-insulin-dependent) diabetes mellitus. 282 66

Acanthosis nigricans is a marker for disorders of insulin action, endocrine abnormalities, and cancer of internal organs. To evaluate the clinical significance of this marker the systemic alterations and clinical features of 26 patients with acanthosis nigricans seen at two institutions were reviewed. Most subjects affected by acanthosis nigricans were female (20 patients), Caucasian (22 patients), in the third decade of life (13 patients), and overweight (24 patients greater than 120 percent ideal body weight). Gonadal disease, present in 17 patients, was expressed as polycystic ovary syndrome (11 cases), disorders of prolactin secretion (two cases, one with polycystic ovary syndrome), streak gonads (one case), and hypogonadism of the male (four cases). Thyroid disease and tinea versicolor were present in four patients each. Three patients were receiving insulin therapy for diabetes mellitus, and in two additional patients diabetes mellitus was detected during the diagnostic workup. All patients had elevated fasting insulin levels; most of them also had an exaggerated insulin response to a glucose load. Two of 18 patients tested had antibodies against the insulin receptor in the circulation. Skin biopsy of acanthosis nigricans lesions from all 26 patients showed a typical pattern of hyperkeratosis, acanthosis, and epidermal papillomatosis. Colloidal iron staining showed glycosaminoglycan infiltration of the papillary dermis (21 of 21 cases), consisting mainly of hyaluronic acid. It is concluded that: (1) hyperinsulinenemia and local dermal glycosaminoglycan deposition are regular features in acanthosis nigricans and (2) patients with acanthosis nigricans should be screened for diabetes mellitus, gonadal disease, and hypothyroidism.
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PMID:Spectrum of endocrine abnormalities associated with acanthosis nigricans. 367 58

In man, the assay of insulin receptors is performed on circulating monocytes or erythrocytes. In physiology, insulin binding decreases with age; it is lower in women during the luteal phase of the menstrual cycle or during administration of oestrogen-progestogen oral contraceptives; it exhibits diurnal variation; it increases after physical training; it depends on the diet, being inversely correlated with its carbohydrate content; finally, rapid variations in binding affinity are observed after glucose ingestion or after breakfast. In pathology, obese people are resistant to the effects of insulin and they have decreased numbers of receptors on blood cells; short-term fasting induces an increase in the binding affinity, while a long term hypocaloric diet leads to an increase in receptor numbers. Similarly non-insulin-dependent, maturity onset diabetics, even without overweight, have low numbers of binding sites, which are increased by diet or after treatment by sulfonylureas. In the syndrome of insulin resistance and acanthosis nigricans, there is a decrease in hormone binding, which is either primary (Type A) or is secondary to the effects of circulating antibodies to the insulin receptor (Type B). In acromegaly, insulinomas, liver cirrhosis and acute viral diseases the binding of insulin is decreased. On the contrary, variable results have been reported in cases of lipoatrophic diabetes, leprechaunism, uremia and glucocorticoid administration. Finally, an increase in insulin receptors has been observed in anorexia nervosa and in insulino-penic diabetes.
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PMID:[The insulin receptors of the blood cells and their study in disease states in man (author's transl)]. 734 Jun 95

PCOS is the most frequent endocrine disorder of premenopausal women. The common clinical signs of PCOS are hirsutism, menstrual irregularities with chronic anovulation and a trend toward overweight or obesity. Diagnosis is based upon high plasma levels of androgens and the ultrasound image of polycystic ovaries. The high prevalence of PCOS at first degree female relatives suggest an important genetic component of this syndrome. Linking studies in sisters presenting phenotypical traits of PCOS and in their parents allowed the investigation of certain candidate genes presumed to be involved in the physiopathology of PCOS. The genes encoding enzymes involved in androgen synthesis, protein transducers of insulin signals and the paracrine regulating factors of gonadotrophins and ovarian function have been analysed. To date, no determinant gene mutation was reported. However, several loci were detected, especially a locus within the insulin receptor. Mutations or gene polymorphisms and their function remain to be identified. These research attempts should explain the physiopathology of PCOS and open new therapeutic perspectives. The usage of medication increasing the sensitivity to insulin action is an example of applying these particular aspects.
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PMID:[Genetics of the polycystic ovarian syndrome and therapeutic perspectives ]. 1208 37

Alpha(2) Heremans-Schmid glycoprotein (AHSG) is a plasma protein inhibiting the activity of the insulin receptor tyrosine kinase. Ahsg knock-out mice have increased insulin sensitivity and are resistant to diet-induced obesity. We hypothesized that functional variants of the AHSG gene segregating in the human population would reflect variation in body mass index (BMI). We genotyped 356 overweight or obese (BMI: 37.2 [25.0-66.5] kg/m(2)) and 148 lean (BMI: 23.7 [23.4-24.9] kg/m(2)) otherwise healthy Swedish men for three non-synonymous single-nucleotide polymorphisms (SNPs) within exon 6 (rs4917) and exon 7 (rs4918 and Arg299Cys) and one SNP in intron 1 (rs2593813) of the AHSG gene. The G/G genotype for rs2593813 was more common among lean than among obese and overweight individuals (odds ratio = 2.01, P = 0.009), whereas rs2593813 was in strong linkage disequilibrium (|D'| > or = 0.97) with rs4917 and rs4918. Homozygosity for the rs2593813:G-rs4917:Met-rs4918:Ser haplotype conferred an increased risk for leanness (odds ratio=1.90, P = 0.027). rs4917:Met and rs4918:Ser have previously been associated with lower AHSG protein level. A common variant of AHSG, previously associated with a lower AHSG protein level, is thus more common among lean than obese and overweight men, supporting the results from Ahsg knock-out mice, namely, that AHSG modulates body mass.
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PMID:AHSG gene variant is associated with leanness among Swedish men. 1580 95

Childhood NAFLD has become an important childhood liver disease, and it is probably highly prevalent. The full of spectrum of NAFLD has been identified in children. It is not currently known whether or not simple hepatic steatosis in children is benign or whether it evolves to NASH over time. In contrast, childhood NASH certainly can have serious consequences. Cirrhosis is apparently rare in children with NAFLD, but it definitely occurs. Childhood NAFLD may occur in very young children, and there is no female predominance in the pediatric age bracket. Children present with vague abdominal pain, if they have any symptoms at all, but frequently hepatic steatosis is found incidentally on abdominal imaging. Laboratory studies show that serum aminotransferase abnormalities are rather moderate, with serum alanine aminotransferase (ALT) more elevated than serum aspartate aminotransferase (AST). Hypertriglyceridemia is the typical blood lipid abnormality, although hypercholesterolemia may occur. NASH may be more severe in children from certain ethnic groups, including Hispanics and Asians, or in association with certain metabolic disorders characterized by abnormalities in insulin receptor structure or signaling, such as lipodystrophy syndromes. Weight loss through dietary redesign and a regimen of regular exercise remains the mainstay for treatment for childhood NAFLD. A dietary strategy to minimize postprandial hyperinsulinemia and overall fat intake, such as a low glycemic index diet, may be the best dietary strategy. The real efficacy of drug treatments in children requires further investigation. The overriding message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.
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PMID:Non-alcoholic fatty liver disease (NAFLD) in children. 1597 Apr 96

Nonalcoholic fatty liver disease (NAFLD) is likely to reach epidemic proportions in children worldwide in the next decade. NAFLD may be the hepatic aspect of the metabolic syndrome in adults and children. The entire range of liver involvement characterizing NAFLD can occur in children: hepatic macrovesicular steatosis without inflammation, steatosis with inflammation or fibrosis, and cirrhosis. NAFLD may be more severe in children from certain ethnic groups or in association with metabolic disorders characterized by abnormalities in insulin receptor structure and function. Treatment strategies focus on modifying risk factors because specific drug treatments are lacking. Overweight/obesity should be identified as early as possible. Comprehensive clinical management to normalize weight should be instituted immediately to avoid hepatic and nonhepatic complications.
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PMID:Nonalcoholic fatty liver disease in children. 1637 97


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