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)

In recent years, the thiazolidinediones (e.g. rosiglitazone, pioglitazone) have emerged as an exciting novel class of therapeutic agent for the treatment of type 2 diabetes mellitus and the human metabolic syndrome. At first glance, the use of these high-affinity peroxisome proliferator-activated receptor gamma (PPARgamma) agonists, that promote adipogenesis, to treat a group of disorders that typically have their origins in obesity seems counter-intuitive. However, to view PPARgamma simply as a regulator of fat mass, and adipocytes themselves as passive vessels for energy storage, is to ignore an extensive body of data that speaks of the diverse roles of both this receptor and adipose tissue in the maintenance of normal metabolic homeostasis. This article highlights the important clinical and laboratory observations made in human subjects harbouring genetic variations in PPARgamma that have confirmed its pivotal role in the regulation of adipocyte endocrine function, and thus our metabolic response to the environment.
Best Pract Res Clin Endocrinol Metab 2005 Dec
PMID:Peroxisome proliferator-activated receptor gamma and the regulation of adipocyte function: lessons from human genetic studies. 1631 Dec 14

Free fatty acids (FFAs) circulate round the body and represent important nutrients and the key oxidative fuel for the heart and resting skeletal muscle. In addition, FFAs are thought to be potent signalling molecules. Growing evidence indicates that FFAs may be involved in type 2 diabetes mellitus and obesity by mediating insulin resistance. In 1963, it was postulated that accumulated glucose-6-phosphate as a result of increased FFA oxidation leads to decreased glucose uptake. An alternative hypothesis is that increased concentrations of plasma FFA induce insulin resistance in humans through inhibition of glucose transport activity, which appears to be a consequence of decreased insulin receptor substrate-1-associated phosphatidyl inositol 3 kinase activity. Moreover, FFAs can arise locally, and increased intramyocellular and hepatocellular lipids have been shown to be associated with insulin resistance. This paper reviews the main aspects of FFA metabolism in the development of insulin resistance in skeletal muscle and liver, as well as the role of ectopic lipid deposits as a local source of FFAs. Finally, the role of thiazolidinediones as modulators of FFA-induced insulin resistance will be discussed.
Best Pract Res Clin Endocrinol Metab 2005 Dec
PMID:Fatty acids and insulin resistance in muscle and liver. 1631 Dec 21

The purpose of this study was to investigate the association between type 2 diabetes mellitus (DM2) and trabecular volumetric bone mineral density (vBMD) of the thoracic and lumbar spine measured by quantitative computed tomography (QCT) in 483 female (410 with DM2) and 398 male (365 with DM2) adults (age 36-86 years, BMI 16-58, 88% with DM2) in the Diabetes Heart Study. After accounting for familial correlation using generalized estimating equations (GEE), lumbar spine vBMD was positively associated with BMI (r = 0.24, P < 0.0001) and inversely associated with age (r = -0.51, P < 0.0001). In women, age-adjusted thoracic spinal vBMD (mg/ml, mean +/- SE) was higher in diabetics (147.6 +/- 2.3) compared to unaffected individuals (138.6 +/- 3.4) (P = 0.02), with age-adjusted lumbar spinal vBMD showing a similar but non-significant trend (132.9 +/- 2.1 in diabetics vs. 127.2 +/- 3.6 in unaffected individuals, P = 0.15). In contrast, in men, age-adjusted lumbar and thoracic vBMD were not different between diabetics and unaffected controls (lumbar vBMD = 125.0 +/- 1.8 in diabetics and 125.8 +/- 5.6 in unaffected individuals, P = 0.89; thoracic vBMD = 137.4 +/- 2.1 in diabetics vs. 134.2 +/- 5.5 in controls, P = 0.56). After multivariate analysis adjusting for age, sex, race, BMI, physical activity, dietary intake, smoking, and alcohol use, interaction between diabetes status and trabecular vBMD of the spine was no longer observed. In women only, age-adjusted areal BMD (determined by dual X-ray absorptiometry (DXA)) of the spine and hip were significantly higher in diabetics than non-diabetic (all P < 0.05), although the differences disappeared after additional adjustment for BMI. These data suggest that areal BMD measured by DXA and trabecular volumetric BMD measured by QCT are not associated with type 2 diabetes independently from BMI.
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PMID:Type 2 diabetes is not independently associated with spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. 1669 Mar 65

Polycystic ovary syndrome (PCOS) is increasingly being recognized in adolescent girls seeking treatment for signs and symptoms of hyperandrogenism. It is difficult to diagnose PCOS in adolescents, therefore a high index of suspicion is necessary. Timely screening and treatment are crucial because another important component of the syndrome is insulin resistance/hyperinsulinemia increasing the risk for type 2 diabetes, dyslipidemia, and cardiovascular sequelae. Diagnosis of PCOS in adolescents should include a thorough family history, exclusion of other causes of hyperandrogenism, and appropriate laboratory evaluation. The scarcity of controlled clinical trials makes treatment controversial. Therapeutic options include lifestyle intervention, oral contraceptive pills, and insulin sensitizers. Long-term follow-up is needed to determine the effectiveness of these approaches in changing the natural history of the reproductive and metabolic outcomes without causing undue harm.
Best Pract Res Clin Endocrinol Metab 2006 Jun
PMID:Treatment of PCOS in adolescence. 1677 60

Insulin resistance is a feature of a number of clinical disorders, including type 2 diabetes/glucose intolerance, obesity, dyslipidaemia and hypertension clustering in the so-called metabolic syndrome. Insulin resistance in skeletal muscle manifests itself primarily as a reduction in insulin-stimulated glycogen synthesis due to reduced glucose transport. Ectopic lipid accumulation plays an important role in inducing insulin resistance. Multiple defects in insulin signalling are responsible for impaired glucose metabolism in target tissues of subjects with features of insulin resistance. Inflammatory molecules and lipid metabolites inhibit insulin signalling by stimulating a number of different serine kinases which are responsible for serine phosphorylation of Insulin Receptor Substrate-1 (IRS-1).
Best Pract Res Clin Endocrinol Metab 2006 Dec
PMID:Pathophysiology of insulin resistance. 1716 38

Demographic trends with longer life expectancy and a lifestyle characterized by low physical activity and high-energy food intake contribute to an increasing incidence of diabetes mellitus and osteoporosis. Diabetes mellitus is a risk factor for osteoporotic fractures. Patients with recent onset of type 1 diabetes mellitus may have impaired bone formation because of the absence of the anabolic effects of insulin and amylin, whereas in long-standing type 1 diabetes mellitus, vascular complications may account for low bone mass and increased fracture risk. Patients with type 2 diabetes mellitus display an increased fracture risk despite a higher BMD, which is mainly attributable to the increased risk of falling. Strategies to improve BMD and to prevent osteoporotic fractures in patients with type 1 diabetes mellitus may include optimal glycemic control and aggressive prevention and treatment of vascular complications. Patients with type 2 diabetes mellitus may additionally benefit from early visual assessment, regular exercise to improve muscle strength and balance, and specific measures for preventing falls.
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PMID:Osteoporosis in patients with diabetes mellitus. 1750 67

Although the association between diabetes and osteoporosis has been studied, it remains unclear if the pathogenesis of vertebral fractures in patients with type 2 diabetes would be similar to those without diabetes. One hundred and fifty female diabetic patients without apparent proteinuria as well as 716 women without diabetes (control group) were examined by lateral thoracic and lumbar spine radiographs as well as dual-energy X-ray absorptiometry. Vertebral fractures were found in 26 (17.3%) and 158 (22.1%) subjects in the diabetic and control groups, respectively. Diabetic patients had higher absolute and age-matched (Z score) values of lumbar bone mineral density (L-BMD) than controls despite their significantly higher mean age. By receiver operating characteristic (ROC) analysis, the absolute L-BMD values for detecting vertebral fractures were higher and sensitivity and specificity were lower in diabetic patients than controls (0.816 g/cm2 vs. 0.716 g/cm2 and 66.0% vs. 74.8%, respectively). Logistic regression analysis adjusted for age, body weight, and height also showed that L-BMD was not significantly associated with the presence of vertebral fractures in diabetic patients (odds ratio [OR] = 0.61, 95% confidence interval [CI] 0.34-1.09 per standard deviation increase, P = 0.0954), in contrast to the significant association in controls (OR = 0.23, 95% CI 0.16-0.33, P < 0.0001). These results show that L-BMD is not sensitive enough to assess the risk of vertebral fractures in female diabetic patients and suggest that bone fragility not defined by BMD might be related to the risk of vertebral fractures in them.
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PMID:Bone mineral density is not sensitive enough to assess the risk of vertebral fractures in type 2 diabetic women. 1754 36

Diabetic macular edema (DME) is the major cause of vision loss in patients with diabetic retinopathy (DR). The purpose of this study was to assess the prevalence of DR and DME in a community in China and to analyze the characteristics of their optical coherence tomography (OCT) images. This study was an incidence survey based on data from 108,132 residents living in the Beixinjing District, Shanghai, China. Patients with DME came from the local health network. OCT was performed in 151 eyes of 100 type 2 diabetes patients with DR and 102 eyes of normal control subjects. Totally 795 cases were examined, and 215 of them were diagnosed to have DR. The average thickness of the macular fovea was 195.56 microm in 151 eyes from 100 random samples. Forty-six eyes had macular thickening. The statistical analysis showed that there was a positive correlation between the thickness of the macular fovea and -log of best-corrected visual acuity (r = 0.2869, p = 0.0004) as well as the severity of DR (p = 0.0003). However, there was no statistical significance between DME and posterior vitreous detachment. The images of OCT in DME included 3 types. Best-corrected visual acuity moderately correlated with retinal thickness. The macular thickness correlated with the severity of DR but not with posterior vitreous detachment.
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PMID:The status of diabetic retinopathy and diabetic macular edema in patients with type 2 diabetes: a survey from Beixinjing District of Shanghai city in China. 1809 78

Over the last 15 years, a number of long-term health risks associated with reduced fetal growth have been identified, including cardiovascular diseases, hypertension, dyslipidaemia and type 2 diabetes. A common feature of these conditions is insulin resistance, which is thought to play a pathogenic role. However, despite abundant data in the literature, it is still difficult to trace the pathway by which fetal events, environmental or not, may lead to increased morbidity later in life. To explain this association, several hypotheses have been proposed pointing to the role of a detrimental fetal environment, a genetic susceptibility or an interaction between the two, and of the particular dynamic changes in adiposity that occur during catch-up growth. The relative impact of early postnatal events in relation to fetal growth has to be considered for designing health policy strategies for early interventions aimed at decreasing disease risk throughout life.
Best Pract Res Clin Endocrinol Metab 2008 Jun
PMID:Pathophysiology of insulin resistance in subjects born small for gestational age. 1853 89

Although patients with type 2 diabetes (T2DM) have an increased risk of hip fracture, risk of vertebral fracture (VF) and its association with BMD are still unclear. We examined Japanese T2DM patients (161 men >50 yr and 137 postmenopausal women) and non-DM controls (76 and 622, respectively) by lateral spine radiography and DXA at the lumbar spine (L), femoral neck (FN), and radius (R). Logistic regression analysis adjusted for age, body mass index, and L-BMD showed that the presence of T2DM was an independent risk factor for prevalent VFs in women (OR = 1.86, p = 0.019) and men (OR = 4.73, p < 0.001). BMD at any site, however, was not significantly associated with the presence of prevalent VFs in T2DM patients, in contrast to the significant association in controls (at least p = 0.010). Comparison of T2DM patients with and without VFs showed no significant differences in BMD values, bone markers, or diabetes status. Receiver operating characteristic analysis showed that the absolute L-, FN-, and R-BMD values for detecting prevalent VFs were higher in T2DM patients than controls, whereas their sensitivity and specificity were lower. T2DM patients may have an increased risk of VFs independent of BMD or diabetic complication status, suggesting that bone quality may define bone fragility in T2DM.
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PMID:Diabetic patients have an increased risk of vertebral fractures independent of BMD or diabetic complications. 1904 38


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