Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Optimal patient selection for laparoscopic adjustable gastric banding with the LAP-BAND (INAMED Health, Santa Barbara, CA) enables maximization of results for patients most suited to the procedure and avoidance of unsatisfactory outcomes for inappropriate candidates. We have investigated potential predictors of outcomes in our patients to look for associations with weight loss. We have also reviewed published data for additional predictors. This analysis has revealed a number of conditions associated with a significantly lower percent excess weight loss (%EWL) than experienced in the overall group. These include increasing age, increasing body mass index (BMI), hyperinsulinemia, insulin resistance, type 2 diabetes, and polycystic ovary syndrome. There was also less weight loss if the SF-36 quality-of-life measure showed a poor physical activity score, high pain score, or poor general health score. However, in all these conditions, the effect was small in comparison with the benefits achieved by these patients, and was judged insufficient to preclude this approach to treatment of their obesity. A number of conditions were found to have no relation to weight loss after LAP-BAND placement. These included sex, presence of mental illness, most comorbidities except those linked to insulin resistance, previous bariatric surgery, and sweet-eating behavior. The value of psychologic assessment to predict outcomes could not be established. The superobese (BMI >50) achieved a lower %EWL at 1 year after LAP-BAND placement compared with those with BMI <50, but there were no differences at the 2-, 3-, and 4-year follow-ups.
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PMID:Selecting the optimal patient for LAP-BAND placement. 1252 45

A 1991 National Institutes of Health Consensus Conference concluded that severely obese adults could be eligible for bariatric surgery if they had a body mass index (BMI) > or =35 kg/m(2) with or > or =40 kg/m(2) without obesity comorbidity. It was thought at that time that there were inadequate data to support bariatric surgery in severely obese adolescents. An estimated 25% of children in the United States are obese, a number that has doubled over a 30-year period. Very little information has been published on the subject of obesity surgery in adolescents. Therefore we reviewed our 20-year database on bariatric surgery in adolescents. Severely obese adolescents, ranging from 12 to less than 18 years of age, were considered eligible for bariatric surgery according to the National Institutes of Health adult criteria. Gastroplasty was the procedure of choice in the initial 3 years of the study followed by gastric bypass, which was found to be significantly more effective for weight loss in adults. Distal gastric bypass (D-GBP) was used in extremely obese patients (BMI > or =60 kg/m(2)) before 1992 and long-limb gastric bypass (LL-GBP) was used for superobese patients (BMI > or =50 kg/m(2)) after 1992. Laparoscopic gastric bypass was used after 2000. Thirty-three adolescents (27 white, 6 black; 19 females, 14 males) underwent the following bariatric operations between 1981 and June 2001: horizontal gastroplasty in one, vertical banded gastroplasty in two, standard gastric bypass in 17 (2 laparoscopic), LL-GBP in 10, and D-GBP in three. Mean BMI was 52 +/- 11 kg/m(2) (range 38 to 91 kg/m(2)), and mean age was 16 +/- 1 years (range 12.4 to 17.9 years). Preoperative comorbid conditions included the following: type II diabetes mellitus in two patients, hypertension in 11, pseudotumor cerebri in three, gastroesophageal reflux in five, sleep apnea in six, urinary incontinence in two, polycystic ovary syndrome in one, asthma in one, and degenerative joint disease in 11. There were no operative deaths or anastomotic leaks. Early complications included pulmonary embolism in one patient, major wound infection in one, minor wound infections in four, stomal stenoses (endoscopically dilated) in three, and marginal ulcers (medically treated) in four. Late complications included small bowel obstruction in one and incisional hernias in six patients. There were two late sudden deaths (2 years and 6 years postoperatively), but these were unlikely to have been caused by the bariatric surgical procedure. Revision procedures included one D-GBP to gastric bypass for malnutrition and one gastric bypass to LL-GBP for inadequate weight loss. Regain of most or all of the lost weight was seen in five patients at 5 to 10 years after surgery; however, significant weight loss was maintained in the remaining patients for up to 14 years after surgery. Comorbid conditions resolved at 1 year with the exception of hypertension in two patients, gastroesophageal reflux in two, and degenerative joint disease in seven. Self-image was greatly enhanced; eight patients have married and have children, five patients have completed college, and one patient is currently in college. Severe obesity is increasing rapidly in adolescents and is associated with significant comorbidity and social stigmatization. Bariatric surgery in adolescents is safe and is associated with significant weight loss, correction of obesity comorbidity, and improved self-image and socialization. These data strongly support obesity surgery for those unfortunate individuals who may have difficulty obtaining insurance coverage based on the 1991 National Institutes of Health Consensus Conference statement.
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PMID:Bariatric surgery for severely obese adolescents. 1255 91

The author reviews the history of the term polycystic ovaries syndrome. He emphasizes the importance of insulin resistance in this disease. According to more recent criteria for the definition of the syndrome suffices the finding of hyperandrogenism, an irregular cycle (after elimination of other classical causes of this condition) and insulin resistance. The frequency of the disease varies in different populations up to 10%. It is significantly associated in particular with type 2 diabetes and obesity. The molecular biology of the syndrome is obscure. The metabolic syndrome as well as the polycystic ovaries syndrome have partly a genetic pathogenesis as well as an environmentally induced participation caused by stress. The polycystic ovaries syndrome is nowadays unequivocally an atherogenic syndrome and is a unit very close to Reaven's metabolic syndrome X or is part of this syndrome.
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PMID:[Metabolic aspects of the polycystic ovary syndrome]. 1264 30

Type 2 diabetes mellitus is an increasingly prevalent disorder associated with multiple metabolic derangements. Insulin resistance is the most prominent feature common in both type 2 diabetes and its associated metabolic abnormalities. Until 1995, the only therapeutic interventions available in the United States were the insulin secretagogues sulfonylureas and insulin. With the introduction of metformin in the United States in the mid-1990s and the subsequent advent of thiazolidinediones, an opportunity exists to address and directly reverse, at least in part, the defects in insulin action seen in individuals with type 2 diabetes. Evidence shows that insulin sensitizers not only have beneficial effects on glycemic control but also have multiple effects on lipid metabolism and atherosclerotic vascular processes that could prove to be beneficial. We discuss safety issues of these agents, their potential use in preventing onset and progression of diabetes, and their use in other related metabolic conditions such as polycystic ovary syndrome.
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PMID:Insulin sensitizers. 1268 92

Polycystic ovary syndrome (PCOS) is associated with hyperinsulinemia, insulin resistance (IR), increased risk of glucose intolerance, and type 2 diabetes. Family studies have indicated a genetic susceptibility to PCOS. The aims of this study were 1) to assess glucose tolerance status, gonadotropins, and androgens in first degree relatives of patients with PCOS; and 2) to assess IR in normal glucose tolerant (NGT) family members. One hundred two family members of 52 patients with PCOS [Mothers(PCOS) (n = 34; mean age, 46.5 yr; mean body mass index (BMI), 28.8 kg/m(2)), Fathers(PCOS) (n = 24; mean age, 50.4 yr; mean BMI, 27.5 kg/m(2)), Sisters(PCOS) (n = 19; mean age, 25.1 yr; mean BMI, 22.9 kg/m(2)), and Brothers(PCOS) (n = 25; mean age, 23.7 yr; mean BMI, 22.5 kg/m(2))] and 82 unrelated healthy control subjects without a family history of diabetes or PCOS (4 age- and weight-matched subgroups, i.e. Control(MothersPCOS), Control(FathersPCOS), Control(SistersPCOS), and Control(BrothersPCOS)) were studied. Glucose and insulin (at baseline and during a 75-g, 2-h oral glucose tolerance test) were measured. IR was assessed by fasting insulin (FI), fasting glucose to insulin ratio (FGI), homeostatic model assessment (HOMA IR), and area under the curve for insulin during the oral glucose tolerance test (AUC(insulin)) in NGT Mothers(PCOS), Fathers(PCOS), Sisters(PCOS), Brothers(PCOS), and matched control subgroups. Including the prestudy-diagnosed 3 mothers and 2 fathers with diabetes, diabetes and impaired glucose tolerance (IGT) were noted in 16% and 30% of Mothers(PCOS) and 27% and 31% of Fathers(PCOS), respectively. There was no diabetes in Sisters(PCOS) and Brothers(PCOS). IGT was found in 5% of Sisters(PCOS). Impaired fasting glucose was found in 3% of Mothers(PCOS) and 4% of Brothers(PCOS). The analysis of NGT family members showed that Mothers(PCOS) had higher FI (P < 0.05), HOMA IR (P < 0.05), and AUC(insulin) (P < 0.01) and lower FGI (P < 0.05) than Control(MothersPCOS), whereas all IR parameters were comparable between Fathers(PCOS) and their matched control subgroup. Sisters(PCOS) had higher FI (P < 0.05), HOMA IR (P < 0.01), and AUC(insulin) (P < 0.05) and lower FGI (P < 0.01), and Brothers(PCOS) had higher AUC(insulin) (P < 0.01) than their matched control subgroups, respectively. Mothers(PCOS) had higher testosterone levels than Control(MothersPCOS) (P < 0.01 and P < 0.05 for pre- and postmenopausal women, respectively). Sisters(PCOS) had higher LH (P < 0.01), testosterone (P < 0.001), androstenedione (P < 0.01), and dehydroepiandrosterone sulfate (P < 0.05) levels than Control(SistersPCOS). There was no difference in gonadotropin and androgen levels in Fathers(PCOS) compared with Control(FathersPCOS) or in Brothers(PCOS) compared with Control(BrothersPCOS). Our results suggest that 1) first degree relatives of patients with PCOS may be at high risk for diabetes and glucose intolerance; 2) NGT female family members have insulin resistance; and 3) mothers and sisters of PCOS patients have higher androgen levels than control subjects. We propose that the high risks of these impairments warrant screening in first degree relatives of patients with PCOS.
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PMID:Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. 1272 50

The emerging epidemic of type 2 diabetes (T2DM) in young people reflects increasing rates of obesity and parallels the increasing frequency of T2DM in adults. As in adults, T2DM in children is part of the insulin resistance syndrome that includes hyperandrogenism seen as premature adrenarche and polycystic ovary syndrome, hypertension, dyslipidemia, and other atherosclerosis risk factors. Recent studies in children document risk factors for T2DM, and associated cardiovascular risk factors, including obesity, family history, diabetic gestation, and underweight or overweight for gestational age. Genetically determined insulin resistance or limited beta-cell reserve has been demonstrated in high-risk individuals, including first-degree relatives of girls with premature adrenarche. This genetic background, considered advantageous in a feast-and-famine existence (the thrifty genotype), is rendered detrimental with abundant food and physical inactivity, a lifestyle demonstrated to be typical of families of children with T2DM. The increasing incidence of T2DM in children and adolescents threatens to become a major public health problem. Risk factors for cardiovascular disease, hypertension, hyperlipidemia, and microalbuminuria are present at diagnosis of T2DM in Native American adolescents, indicating that insulin resistance has been present for some time before the diagnosis of diabetes was made. Case finding is likely to be beneficial in high-risk youths. Treatment is the same as that of adults. The only data on use of oral hypoglycemic agents in children have been with metformin. Community and governmental efforts to educate all children and their parents about the need for physical activity and dietary modification are essential to control this epidemic.
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PMID:Type 2 diabetes in children. 1276 53

Pregnancy increases requirements for insulin secretion, increasing insulin resistance and demands on pancreatic b cells, promoting development of gestational diabetes (GD), particularly in women with preexisting insulin resistance, commonly in women with polycystic ovary syndrome. Preliminary studies suggest that metformin may have the unique potential to prevent the development of GD. We postulate that interventions that reduce insulin resistance and lower requirements for endogenous insulin secretion can preserve b-cell function and prevent the development of type 2 diabetes mellitus.
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PMID:Metformin and gestational diabetes. 1286 93

In 138 oligo-amenorrheic white women with polycystic ovary syndrome (PCOS) (31+/-9-years-old), our first specific aim was to assess the incidence of the metabolic syndrome and to compare metabolic syndrome abnormalities in women with PCOS to those in the National Health and Nutrition Examination Survey (NHANES) III cohort of 1,887 white women. Our second aim was to determine whether metformin (2.55 g/d) and a diet of 1,500 calories, 26% protein, 44% carbohydrate (42% of carbohydrate complex), 30% fat (polyunsaturate/saturate ratio [P/S]=2/1), would ameliorate metabolic syndrome abnormalities in women with both PCOS and metabolic syndrome. The metabolic syndrome was present in 64 (46%) of the women with PCOS. In these 64 women, there were abnormalities in waist circumference (98%), high-density lipoprotein cholesterol (HDL-C) (95%), blood pressure (70%), triglycerides (56%), and glucose (11%). In these 64 women, mean +/- SD waist circumference was 116+/-15 cm, triglyceride 192+/-152 mg/dL, HDL-C 39+/-7 mg/dL, systolic blood pressure 131+/-13 mm Hg, diastolic blood pressure 83+/-7 mm Hg, and serum glucose 94+/-22 mg/dL. Serum insulin was high (>17 microU/mL) in 42 of the 64 women (66%). After age adjustment, 46.4%+/-4.2% of women with PCOS had the metabolic syndrome (> or =3 abnormalities) versus 22.8%+/-1.1% of NHANES III women, P<.0001 versus 6% of 20 to 29-year-old and 15% of 30 to 39-year-old NHANES III women. Of the 64 women with both PCOS and the metabolic syndrome, 50 had follow-up studies after an average of 6 months on metformin and diet. At 6 months follow-up, mean percent reductions were as follows: body weight 4.7% (111 to 106 kg, P<.0001), triglycerides 14% (197 to 136 mg/dL, P=.0001), systolic blood pressure 5.2% (131 to 124 mm Hg, P=.0002), diastolic blood pressure 6% (83 to 77 mm Hg, P=.0007), and insulin 31% (25 to 17 microU/mL, P<.0001); mean percent HDL-C increased 6% (39 to 41 mg/dL, P=.013). Of these 50 women, 29 had pretreatment baseline abnormal triglycerides (> or =150 mg/dL), 47 had low HDL-C (<50 mg/dL), 26 had high systolic blood pressure (> or =130 mm Hg), 16 had high diastolic blood pressure (> or =85 mm Hg), and 5 had glucose > or = 110 mg/dL. On metformin plus diet at 6 months, triglycerides moved within guidelines in 10 of 29 (34%) women, HDL-C in 6 of 47 (13%), systolic blood pressure in 16 of 26 (62%), diastolic blood pressure in 10 of 16 (63%), and glucose in 3 of 5 (60%). Metformin and diet ameliorate many of the features of the metabolic syndrome, present in 46% of women with PCOS in the current study, and should reduce risk for atherothrombosis and type 2 diabetes mellitus (DM) in PCOS.
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PMID:Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. 1287 Jan 69

Polycystic ovary syndrome (PCOS), the main androgen disorder in women, has been suggested to be associated with a high risk of developing cardiovascular disease and type 2 diabetes. In many PCOS patients, overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance, and has been identified as a target for new therapeutic strategy, including early change in lifestyle. Early biochemical marker(s) for identifying at-risk patients will be useful for prevention studies. The main goal of the present study was to search for such tool(s). We investigated 16 nonobese PCOS women by performing euglycemic hyperinsulinemic clamp and measuring insulin levels during fasting and oral glucose tolerance test, as well as the serum concentrations of SHBG, leptin, and adiponectin, the newly identified adipose factors. Eight of the 16 patients had a steady-state glucose disposal rate less than 8.5 mg/kg.min, the lowest normal value for nonobese control women. These insulin-resistant patients had significant higher body mass index (BMI) and waist-to-hip ratio (WHR), and lower high-density lipoprotein cholesterol and SHBG levels. As expected, glucose disposal correlated negatively with BMI (P = 0.01), WHR (P = 0.01), and fasting insulin level (P = 0.003). On stepwise regression analysis, however, the glucose-to-insulin ratio (GIR) emerged as the strongest independent parameter to appraise insulin resistance (R(2) = 0.61). SHBG level correlated positively with GIR (P < 0.001) and negatively with BMI (P = 0.003) but did not correlate with either insulin response during the glucose tolerance test or plasma leptin and/or adiponectin levels. In contrast, BMI was the only independent predictive parameter of SHBG (P = 0.003, R(2) = 0.73). Interestingly, plasma adiponectin levels were positively associated with glucose disposal rate (P = 0.043) and negatively with WHR (P = 0.024), waist circumference being the best predictor of adiponectin level (P < 0.01). Leptin level correlated only with BMI (r = 0.62, P = 0.01). This study confirmed that insulin resistance, despite the lack of obesity as such, is clearly present in many PCOS women, and demonstrated that GIR is the best predictor for insulin resistance. It was also shown that adiponectin level is a good indicator of abdominal fat mass and is associated to insulin resistance. Finally, low SHBG levels in PCOS are intimately associated with BMI, suggesting that some signal(s) from the adipose tissue, independent of adiponectin and leptin, may regulate liver production of SHBG.
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PMID:Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome. 1291 46

Metformin, a biguanide, has been available in the US for the treatment of type 2 diabetes mellitus for nearly 8 years. Over this period of time, it has become the most widely prescribed antihyperglycaemic agent. Its mechanism of action involves the suppression of endogenous glucose production, primarily by the liver. Whether the drug actually has an insulin sensitising effect in peripheral tissues, such as muscle and fat, remains somewhat controversial. Nonetheless, because insulin levels decline with metformin use, it has been termed an 'insulin sensitiser'. Metformin has also been shown to have several beneficial effects on cardiovascular risk factors and it is the only oral antihyperglycaemic agent thus far associated with decreased macrovascular outcomes in patients with diabetes. Cardiovascular disease, impaired glucose tolerance and the polycystic ovary syndrome are now recognised as complications of the insulin resistance syndrome, and there is growing interest in the management of this extraordinarily common metabolic disorder. While diet and exercise remain the cornerstone of therapy for insulin resistance, pharmacological intervention is becoming an increasingly viable option. We review the role of metformin in the treatment of patients with type 2 diabetes and describe the additional benefits it provides over and above its effect on glucose levels alone. We also discuss its potential role for a variety of insulin resistant and prediabetic states, including impaired glucose tolerance, obesity, polycystic ovary syndrome and the metabolic abnormalities associated with HIV disease.
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PMID:Metformin: new understandings, new uses. 1293 Jan 61


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