The metabolic syndrome: Insulin resistance

Insulin resistance is the most accepted unifying theory explaining the pathophysiology of the metabolic syndrome. However, epidemiologic studies indicate that a substantial proportion of patients with the metabolic syndrome do not have evidence of insulin resistance, and the correlation between insulin resistance and individual components of the syndrome is weak to moderate. Insulin resistance may play an important role in the development of hyperglycemia and dyslipidemia, which can further aggravate insulin resistance. The implication of insulin resistance in hypertension appears to be less strong than its role in causing hyperglycemia and dyslipidemia. Obesity may be another pathogenic factor in the metabolic syndrome that may help initiate or worsen insulin resistance. However, like insulin resistance, obesity is not universal in the metabolic syndrome, and many obese subjects do not have metabolic abnormalities. This review provides an update on the relationship between insulin resistance and main components of the metabolic syndrome: hyperglycemia, dyslipidemia, hypertension, and obesity.     

Insulin and GH secretion in adolescent girls with irregular cycles: polycystic vs multifollicular ovaries

In the present study insulin (I) and GH secretion was studied in a group of twenty-five young adolescent girls (mean age: 15 +/- 0.23 yr) with cycle irregularity associated to clinical signs of hyperandrogenism in comparison with that observed in eleven normal matched subjects with regular menses. All patients underwent basal hormone measurements and, on two consecutive days, an oral glucose tolerance test (OGTT) and a GHRH iv test. Therefore, all subjects had a transabdominal US scan for the measurement of ovarian volume and the characterization of ovarian morphology. On the basis of the US examination we found patients with polycystic ovaries (PCO-like group) and subjects with multifollicular ovaries (MFO group). PCO-like group exhibited T (p<0.01) and LH (p<0.05) plasma levels higher than control group and the highest free androgen index (FAI) values (13 +/- 0.87). All patients with irregular menses showed plasma concentrations of AUC for I (AUC-I) significantly higher in respect to control group (7359.4 +/- 709 vs 5447 +/- 431 microIU/ml x 180 min, p<0.01) as well as both PCO-like group and MFO group did (p<0.001 and p<0.01) respectively. MFO group showed higher values of the AUC for GH (AUC-GH) (2809 +/- 432 ng/ml x 120 min) in respect to controls (1708 +/- 208 ng/ml x 120 min, p<0.05) and PCO-like subjects (p<0.001), who on the contrary showed the lowest AUC-GH values (618 +/- 119 ng/ml x 120 min). In conclusion, PCO-like patients associated hyperinsulinemia with a blunted GH secretion while MFO patients had higher GH secretion associated with higher AUC-I values in a way suggesting an immature and still developing reproductive system.     

Insulin resistance and metabolic syndrome

The metabolic syndrome represents a complex combination of the symptoms obesity, insulin resistance, dyslipoproteinemia, hypertension, and type 2 diabetes. These components have a heterogeneous genetic basis and appear to be closely linked. Obesity is determined by a polygenic constellation and produces insulin resistance, hypertension and dyslipidemia. In addition, defects in the signal transduction of insulin appear to aggravate the insulin resistance independent of obesity. Type 2 diabetes is produced by a third genetic predisposition and is precipitated by the failure of pancreatic beta-cell to compensate insulin resistance. Because prevalence and course of the diabetes markedly depend on the extent of obesity and insulin resistance, these symptoms of the metabolic syndrome represent crucial targets for preventive and therapeutic strategies.     

Insulin sensitivity and its relation to hormones in adolescent boys and girls

Background and AimsA subset of obese individuals lacks cardiometabolic impairment. We aimed to analyze hormonal profiles of insulin-sensitive obese (ISO) and insulin-resistant obese (IRO) adolescents and determine hormonal predictors of homeostasis model of insulin resistance (HOMA-IR).Materials and MethodsA threshold of 3.16 of HOMA-IR was used to classify ISO (< 3.16) IRO (≥ 3.16). In 702 individuals aged 13–18 years (55.8% girls) anthropometric and laboratory [blood glucose, insulin, thyrotropin (TSH), free thyroxine (fT4), free triiodothyronine (fT3), sex hormone-binding globulin (SHBG), steroid hormones, luteinizing hormone, follicle stimulating hormone, prolactin, ghrelin, glucose-dependent insulinotropic polypeptide, glucagon-like-peptide 1glucagon, leptin, resistin, visfatin, leptin, adiponectin and adipsin] assessments were performed. Orthogonal projections to latent structures and Mann–Whitney tests with Bonferroni correction were applied for statistical analysis.Results52.6% girls and 42.9% boys were insulin sensitive. In the predictive model of HOMA-IR thyroid function tests, adiponectin, ghrelin and leptin concentrations played an important role in both genders. Prolactin, testosterone and glucagon contributed to the model only in boys, while progesterone and dehydroepiandrosterone sulfate levels only in girls. After Bonferroni correction levels of leptin, adiponectin, leptin/adiponectin ratio, SHBG and fT4/TSH ratio in both genders, testosterone and glucagon levels in boys and levels of TSH and fT3 in girls were related to insulin sensitivity.ConclusionMetabolic health defined by HOMA-IR is partly predicted by various hormones. Some of them are gender specific. Free T4/TSH and leptin/adiponectin ratios are related to insulin sensitivity in both genders.     

Insulin resistance: metabolic mechanisms and consequences in the heart

Insulin resistance is a characteristic feature of obesity and type 2 diabetes mellitus and impacts the heart in various ways. Impaired insulin-mediated glucose uptake is a uniformly observed characteristic of the heart in these states, although changes in upstream kinase signaling are variable and dependent on the severity and duration of the associated obesity or diabetes mellitus. The understanding of the physiological and pathophysiological role of insulin resistance in the heart is evolving. To maintain its high energy demands, the heart is capable of using many metabolic substrates. Although insulin signaling may directly regulate cardiac metabolism, its main role is likely the regulation of substrate delivery from the periphery to the heart. In addition to promoting glucose uptake, insulin regulates long-chain fatty acid uptake, protein synthesis, and vascular function in the normal cardiovascular system. Recent advances in understanding the role of metabolic, signaling, and inflammatory pathways in obesity have provided opportunities to better understand the pathophysiology of insulin resistance in the heart. This review will summarize our current understanding of metabolic mechanisms for and consequences of insulin resistance in the heart and will discuss potential new areas for investigating novel mechanisms that contribute to insulin resistance in the heart.     

NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome

Nonalcoholic steatohepatitis (NASH) is often linked with disorders that are clearly associated with insulin resistance (IR): obesity, type 2 diabetes mellitus, and hypertriglyceridemia. We tested the hypotheses that (1) IR is an essential requirement for the development of NASH and (2) a high association between IR and liver disease is relatively specific for NASH. We measured body mass index (BMI), waist/hip ratio, and fasting serum lipid, insulin, C-peptide, and glucose levels in 66 patients with NASH (21 with advanced fibrosis and 45 with mild fibrosis). IR was determined by the homeostasis model assessment (HOMA). We also determined the strength of the association of NASH with insulin resistance syndrome (IRS) as defined by World Health Organization criteria. To assess whether the finding of IR was relatively specific to NASH rather than simply to obesity or liver disease, we compared the results of a subset of 36 patients with less-severe NASH with 36 age- and sex-matched patients with chronic hepatitis C virus (HCV) of comparable fibrotic severity. IR was confirmed in 65 patients (98%) with NASH, and 55 (87%) fulfilled minimum criteria for IRS. IR was found in lean as well as in overweight and obese patients. The IR values and the prevalence of IRS (75% vs. 8.3%) were significantly higher in those with NASH than in comparable cases of HCV. Hyperinsulinemia was attributable to increased insulin secretion rather than decreased hepatic extraction. In conclusion, most patients with NASH have IRS, and there is a near-universal association between NASH and IR irrespective of obesity. IR is present in mild as well as advanced cases of NASH but is unusual in chronic HCV of similar fibrotic severity.     

Insulin sensitivity and lipolysis in adolescent girls with poorly controlled type 1 diabetes: effect of anticholinergic treatment

OBJECTIVE: Thyroid hormones (THs) perform essential roles in pituitary function. They regulate anterior pituitary hormone secretion and are also key determinants of pituitary cell proliferation and differentiation. The critical role of deiodinase enzymes, which serve as prereceptor regulators of TH action, remains largely unexplored. Three deiodinase enzymes metabolize active and inactive THs and thereby determine tissue concentrations of the biologically active ligand, tri-iodothyronine (T3). We hypothesized that aberrant expression of deiodinase enzymes and/or altered enzyme activity in pituitary tumours may change tissue concentrations of THs and influence their growth and secretory characteristics. STUDY DESIGN AND PATIENTS: We studied 105 pituitary tumours and 10 normal pituitaries for expression of deiodinase enzyme mRNAs encoding types 1 (D1), 2 (D2) and 3 (D3) using real-time RT-PCR. Enzyme activity data from 20 pituitary samples were also obtained. RESULTS: Pituitary tumours expressed significantly increased D3 mRNA (6.5-fold, P < 0.0005) compared with normal pituitaries. D2 mRNA was also increased 2.6-fold (P = 0.005) in pituitary tumours compared with normals. The rare TSH-secreting pituitary tumour subtype expressed a 13.1-fold excess of D3 mRNA and reduced D2 mRNA (0.1-fold of normal pituitaries). D2 mRNA expression in ACTH-secreting tumours was similarly reduced to 0.1-fold that in normal pituitaries. CONCLUSIONS: Pituitary adenomas express abnormal levels of deiodinase enzymes compared to normal pituitaries. These abnormalities may have functional consequences on pituitary tumour growth. In the case of TSH-secreting pituitary adenomas, the observed pattern of deiodinase mRNA expression may explain the 'resistance' of this tumour type to TH feedback.     

胰岛素抵抗与心肌细胞代谢紊乱

胰岛素抵抗(IR)是2型糖尿病(DM)的重要特征,是胰岛素分泌正常,但主要靶器官组织对一定剂量的胰岛素所产生的生理效应低于正常水平的一种状态。1974年,Hamby等人通过病理研究,首次提出了糖尿病心肌病(DCM)概念,并认为DCM与DM特有的代谢有关。无论是IR还是DM患者,长时间都可以伴有慢性并发症,由冠状动脉非阻塞性血管病变所致的心肌细胞功能障碍和结构改变,伴有左室舒张和(或)收缩功能障碍,这种心肌病变被定义为DCM。尽管现在对DCM的发病机理还不清楚,但是已有证据表明这可能与心肌能量代谢紊乱及系统炎症有关系[1]。本文主要讨论IR…     

Possible risk factors in the development of eating disorders in overweight pre-adolescent girls

OBJECTIVES: To investigate concerns about weight, shape and eating, dietary restraint, self-esteem and symptoms of depression in overweight girls. To investigate the relationship between concerns and self-esteem and depressive symptoms in this group. METHOD: Eighteen overweight girls and 18 average-weight girls completed the child version of the Eating Disorders Examination, the Harter Self-Perception Profile and the Short Moods and Feelings Questionnaire. RESULTS: Overweight girls had more concerns about weight, shape and eating and attempted dietary restraint more often. They had more negative self-esteem related to their athletic competence, physical appearance and global self-worth and more symptoms of depression. There was an association between concerns and self-esteem based on physical appearance in the overweight group. CONCLUSION: Overweight girls show some of the psychological features associated with the development of eating disorders, including a link between concerns and self-esteem based on physical appearance. This may help to explain why childhood obesity increases the risk of a later eating disorder.     

Insulin resistance in H pylori infection and its association with oxidative stress

INTRODUCTION H pylori is a noninvasive, microaerophile, nonspore- forming, and spiral-shaped microorganism. H pylori is associated with severe gastric pathologies, including chronic active gastritis, peptic ulcer, gastric adenocarci- noma and type B low-g…     

Insulin resistance and metabolic syndrome in chronic liver diseases: old entities with new implications

Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.     

中国人高血压个体胰岛素抵抗的影响因素

目的探讨上海地区中国人高血压个体胰岛素抵抗的影响因素.方法 473例(男210 例,女263 例)40岁以上的正常人及高血压患者,将后者根据体重及血脂谱进一步分为4个亚组,即正常体重单纯高血压亚组、正常体重高血压合并高甘油三酯(TG)/低高密度脂蛋白-胆固醇(HDL-C)亚组、超重/肥胖单纯高血压亚组及超重/肥胖高血压合并高TG/低HDL-C亚组.用稳态模式评估法的胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗.结果 (1)校正年龄、性别后,高血压超重/肥胖的个体不论伴发高TG/低HDL-C与否,HOMA-IR均较正常者明显增高(P<0.01);而正常体重单纯高血压、正常体重高血压合并高TG/低HDL-C个体的HOMA-IR与正常者无显著性差异(P>0.05).(2)多元回归分析表明,总体脂、TG对胰岛素抵抗指数的影响最大.结论高血压伴总体脂增加或高血压同时合并总体脂增加和高TG/低HDL-C的个体,具有显著的胰岛素抵抗;而正常体重者,无论是单纯高血压还是高血压与高TG/低HDL-C并存,少见胰岛素抵抗.总体脂增加及高TG是引起高血压个体胰岛素抵抗的主要因素.     

Insulin resistance: a metabolic pathway to chronic liver disease

Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty liver disease (NAFLD), one of the most common causes of chronic liver disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic liver disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic liver disease is associated with multiple features of the metabolic syndrome, and the risk of progressive liver disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the liver (metformin) and in the periphery (thiazolidinediones) are discussed.