医学生物PPT】内分泌疾病研究进展郝立智医师.ppt

Update in Endocrinology,郝 立 智 醫 師 永康榮民醫院新陳代謝科 95-05-05 Annals of internal Medicine: 1 Nov. 2005 | Vol. 143 Issue 9 | P. 673-682,2,Outline,DM Thyroid Disease Lipid-Lowering Therapy Adrenal Function,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,3,Myocardial Perfusion Imaging Should Be Considered To Detect Silent CAD in Diabetic pts (DM Care. 2004;27:1954-61.),ADA guidelines recommend routine exercise ECG stress testing to detect silent CAD in diabetic pts when 2 or more additional risk factors are present. The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study tested the effectiveness of these guidelines. Pts with type 2 DM ranging in age from 50 to 75 years (n = 1123) with no known CAD were randomly assigned to 2 groups: One group (n = 522) underwent standard exercise ECG stress testing followed by ECG-gated regional myocardial perfusion imaging by single-photon emission computed tomography (SPECT) at rest and after exercise, whereas the second group (n = 522) did not undergo testing. Both groups were reevaluated 5 years later.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,4,The results indicated that 22% of the pts who underwent testing (n = 113) were found to have evidence of silent coronary disease on the basis of moderate to large perfusion defects (n = 33), ventricular dilatation, ventricular dysfunction at rest, or adenosine-induced ST-segment depression. The strongest predictors for coronary disease were male sex (odds ratio, 2.5 P 0.03), duration of DM (odds ratio, 5.2 P 0.002), and abnormal response to the Valsalva maneuver (odds ratio, 5.6 P 0.001). The researchers reported that 60% of the pt sample (n = 306) had 2 or more risk factors, which made them eligible for screening by ADA guidelines, whereas 204 pts had fewer than 2 risk factors. Of these 204 pts, 45 had abnormal test results. Thus, CAD would not have been detected in these pts if their physicians used only the ADA guidelines to screen for eligibility for testing.,DM Care. 2004;27:1954-61.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,5,The authors concluded that, on the basis of results of perfusion imaging, more than 20% of asymptomatic pts with type 2 DM have CAD; therefore, the current ADA screening guidelines do not sufficiently address this substantial risk. The findings indicate that stress myocardial perfusion imaging should be considered even in asymptomatic pts on the premise that earlier detection of myocardial ischemia in pts with type 2 DM could reduce morbidity and mortality.,DM Care. 2004;27:1954-61.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,6,Insulin Lispro Was Safe and More Cost-Effective than Standard intensive Care for Management of DKA (Am J Med. 2004;117:291-6. ),The aim of this study was to determine whether DKA requires Tx in an ICU. The specific question was whether Tx of DKA by SC lispro insulin on a medical ward is as safe and effective as low-dose IV insulin therapy in the ICU. The study was a randomized, controlled trial of therapy for 20 pts with DKA. Ten pts were assigned to a regular medical ward and treated with SC lispro insulin (0.3 U/kg of BW initially, followed by 0.1 U/kg /hr until plasma glucose levels decreased to 250 mg/dL or less 14 mmol/L, followed by 0.05 to 0.1 U/kg /hr until plasma pH levels increased to 7.3). The 10 pts randomly assigned to care in an ICU received RI IV. (0.1 U/kg initially, followed by infusions of 0.1 U/kg /hr until plasma glucose levels decreased to 250 mg/dL or less 14 mmol/L, then 0.05 to 0.1 U/kg /hr until plasma pH increased to at least 7.3 and serum bicarbonate levels increased to 18 mmol/L or higher).,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,7,The time required to correct the hyperglycemia and acidosis was the same in the 2 regimens: 7 hours (SD, 3) for the pts receiving lispro insulin compared with 7 hours (SD, 2) for those receiving RI (P = 0.29). The length of stay, incidence of hypoglycemia, and amount of administered insulin were also similar. The ICU regimen was associated with 39% higher hospitalization charges ($14429 compared with $8801). The researchers concluded that Tx of DKA on a routine medical ward with hourly administration of SC lispro insulin is just as safe as standard ICU management and is more cost-effective. Their findings suggest that such strategies could prevent unnecessary use of high-cost ICU beds. Although standard ward management was equally effective in this study, it may not be feasible in most general hospitals given such practical considerations as nursing shortages.,Am J Med. 2004;117:291-6.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,8,HbA1c Should Be Considered an independent and Progressive Risk Factor for CV Disease (Ann intern Med. 2004;141:413-20. ),The aim of this study was to determine whether HbA1c levels are related to CVD and mortality and, consequently, whether glycosylated hemoglobin levels may serve as a predictor for CV events. The authors used an ongoing prospective community-based study of 25623 men and women in Norfolk, United Kingdom, to analyze this relationship in 4662 men and 5570 women. HbA1c levels averaged 8.0% in the participants with DM compared with 5.3% in those without DM. An increase in HbA1c levels of 1 percentage point (for example, from 7.0% to 8.0%) was associated with a statistically significant increased risk for death from any cause (odds ratio, 1.26 95% CI, 1.04 to 1.52). This risk relationship was present at all levels of HbA1c and was independent of all other known risk factors, including DM. Of importance, individuals with HbA1c levels in the range of 5.0% to 6.9% accounted for more than 70% of the increased CV risk attributable to elevated HbA1c levels.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,9,The authors concluded that HbA1c is associated with a progressive and continuous increase in risk for both CV disease and mortality across the entire range of HbA1c values. The study is unique because of the large number of study participants (including many women) and indicates that the threshold level between “normal“ and “abnormal“ HbA1c levels should be revised downward. These data are important because they demonstrate that HbA1c level can be considered an independent and progressive risk factor for CV disease in diabetic pts. An increase in glycosylated HbA1c level of 1 percentage point predicts a 20% to 30% average relative increase in frequency of CV events across the range of HbA1c levels in the study sample. The meta-analysis performed by Selvin and coworkers confirmed these findings.,Ann intern Med. 2004;141:413-20.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,10,Liraglutide Effectively Improves Glycemic Control and Islet Cell Function in Type 2 DM (DM. 2004;53:1187-94. ),This study reports results with a new and novel approach to DM management. Glucagon-like peptide-1 (GLP-1), an incretin mimetic, is a naturally occurring insulin secretagogue that is released by the intestine in response to ingestion of food. Research has shown that GLP-1 agonists that bind to the GLP-1 receptors on cells improve glucose homeostasis by several mechanisms. Unique to the action of GLP-1 is its relationship to serum glucose levels: It stops stimulating insulin secretion after glucose levels normalize, thereby avoiding hypoglycemia. The GLP-1 agonists also inhibit glucagon release, which reduces glycemia after meals. After a person ingests food, the inhibition of glucagon ceases when glucose levels normalize, which reduces the risk for hypoglycemia. The GLP-1 peptide is rapidly degraded, however, and its very short half-life has been a barrier to developing a therapeutic agent. The GLP-1 derivative liraglutide is longer acting because of noncovalent coupling to albumin. This study explored the effects of liraglutide on glycemia, free fatty acids, insulin secretion, and gluconeogenesis.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,11,This study was a double-blind, placebo-controlled crossover trial in 13 pts with type 2 DM treated with SC liraglutide (6 g/kg of BW once daily). Liraglutide therapy significantly reduced 24-hour plasma glucose and glucagon levels without altering free fatty acids or 24-hour insulin secretion rates. This outcome occurs because liraglutide stimulates insulin release primarily during intervals of hyperglycemia and not during the entire 24 hours. Arginine is a potent insulin secretagogue independent of plasma glucose and will also increase serum glucagon levels. In this study, insulin secretion increased in response to arginine without increasing glucagon secretion. Reduced glycogenolysis resulted in decreased glucose release from the liver.,DM. 2004;53:1187-94.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,12,These very exciting (albeit preliminary) findings indicate that the GLP-1 derivative liraglutide effectively improves glycemic control and islet cell function in type 2 DM. This peptide is arguably the most exciting therapeutic agent under consideration for the control of glycemia in type 2 diabetic pts. The reduced plasma glucagon levels may lead to greater insulin sensitivity, which would account for the observed reduction in blood glucose level in the presence of unchanged insulin levels. To confirm both the safety and efficacy of these agents, we must await large-scale clinical trials of longer duration that include a broad range of pts with type 2 DM. Similar results were obtained by Ahren and colleagues, who evaluated a new inhibitor of dipeptidyl peptidase-4, the enzyme that degrades GLP-1 and thereby increases blood levels of GLP-1. In this study, the drug reduced plasma glucagon, plasma glucose, and HbA1c levels.,DM. 2004;53:1187-94.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,13,Rosiglitazone Reduces in-Stent Restenosis in Diabetic pts with CAD (DM Care. 2004;27:2654-60. ),This study evaluated the effect of rosiglitazone on preventing in-stent restenosis in diabetic pts with CAD and coronary stents. The rationale for the study hypothesis is that rosiglitazone, a thiazolidinedione used for therapy for DM, also reduces lipid levels, systemic inflammation, and vascular intimamedia thickness. In this study, pts were randomly assigned to a control group (n = 48) or a rosiglitazone therapy group (n = 47); both groups underwent quantitative coronary angiography at study entry and at 6 months. The rate of restenosis was the primary end point.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,14,Rosiglitazone therapy reduced serum levels of insulin and CRP and the rate of stent restenosis (17.6% with rosiglitazone vs. 38.2% in the control group P = 0.03). Rosiglitazone reduced serum CRP levels by 2.31 mg/L (SD, 2.14) compared with a 0.52 mg/L reduction in the control group (P 0.05). Both groups received adjunctive therapy with statins, exercise, and diet, and both had similar mean levels of HbA1c and serum lipids. The authors concluded that rosiglitazone therapy reduces in-stent restenosis in diabetic pts with CAD. The mechanism of action is likely to be inhibition of the immunomodulators and cytokines associated with atherogenesis. The authors imply that rosiglitazone might represent a relatively safe and inexpensive alternative to brachytherapy or drug-eluting stents.,DM Care. 2004;27:2654-60.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,15,Telmisartan Is Comparable to Enalapril for Protecting Renal Function (N Engl J Med. 2004;351:1952-61. ),This prospective study examined whether angiotensin-receptor blockers are as effective as ACE inhibitors in protecting renal function in pts with type 2 DM. The authors compared telmisartan, an angiotensin-receptor blocker that reduces progression to end-stage renal disease (ESRD) in diabetic pts with nephropathy, with traditional first-line therapy with the ACEI enalapril.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,16,This multicenter, double-blind study randomly assigned 250 diabetic pts to receive 80 mg of telmisartan per day (n = 130) or 20 mg of enalapril per day (n = 120) over 5 years. The pts had early nephropathy; 82% had microalbuminuria, and 18% had macroalbuminuria. The primary end point was a change in GFR. Secondary end points were serum Cr and urine albumin levels, BP, rates of ESRD, CV events, and deaths. After 5 years of follow-up, GFRs had declined at the same rate with telmisartan (17.9 mL/min per 1.73 m2) and enalapril (14.9 mL/min per 1.73 m2). The outcomes for secondary end points were also the same. Both groups experienced adverse effects, and 20 pts in the enalapril group had to discontinue the medication. The authors conservative conclusion was that the renal protective effects of telmisartan are not inferior to those of enalapril. Only 1 short-term study had previously compared these 2 types of drugs.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,17,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,18,Risk for Fetal Loss Is increased in Subclinical Hyperthyroidism (JAMA. 2004;292:691-5. ),The aim of this study was to determine if high circulating levels of thyroid hormone have adverse effects on the fetus in pregnant women with the syndrome of resistance to thyroid hormone (RTH). In this syndrome, circulating levels of thyroid hormone are high, but serum TSH levels are normal (rather than suppressed, as would be expected). The authors asked whether the high serum thyroid hormone levels increased miscarriage rates in these pregnant pts even though they had normal serum TSH levels and were euthyroid. The analogous (and much more common) model for this situation is “subclinical hyperthyroidism“ during pregnancy.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,19,The authors retrospectively compared miscarriage rates in 9 women with the syndrome (high serum free thyroxine and triiodothyronine levels with normal TSH concentrations) with rates in unaffected relatives. Affected women had a miscarriage rate of 22.9% compared with 4.4% (P 0.002) in unaffected relatives. Furthermore, the pregnancies of affected women may result in a healthy, unaffected infant or an infant with the syndrome, depending on whether the abnormal gene is transmitted to the infant. In this study, healthy infants born to women with the syndrome had lower birthweights than those of affected infants. Also, the healthy infants had suppressed TSH levels, whereas the affected infants had detectable serum TSH levels. Thus, the high thyroid hormone levels were nonphysiologic (as indicated by the suppressed TSH levels) and deleterious to the outcome of the pregnancy. The authors concluded that the high thyroid hormone levels that are characteristic of the syndrome are toxic to the fetus and cause a high miscarriage rate. Presumably only fetuses unaffected by the RTH receptor mutation would be vulnerable.,JAMA. 2004;292:691-5.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,20,Although the syndrome of RTH is rare, it is probably a good model for the effects of a much more common problem, “subclinical hyperthyroidism.“ In the United States, subclinical hyperthyroidism is most commonly due to iatrogenic overdose with L-thyroxine. We know that mild deficiency of thyroid hormone (subclinical hypothyroidism) has an adverse effect on infant intelligence and is associated with increased rates of fetal loss. Elegantly employing the model of RTH in pregnancy, this study also demonstrates the potential for fetal loss in subclinical hyperthyroidism. Pregnant women may also be at risk if they have inadequately treated hyperthyroidism associated with Graves disease or nodular goiters.,JAMA. 2004;292:691-5.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,21,Periodic Thyroid Screening Is indicated for Men Receiving Therapy for Hepatitis C (Arch intern Med. 2004;164:2371-6. ),Women who receive interferon and ribavirin for hepatitis C virus (HCV) infection are at increased risk for thyroid dysfunction. This study examined the frequency and outcomes of thyroid dysfunction caused by HCV therapy in men undergoing combination Tx with interferon- 2b and ribavirin. The studys purpose was to determine whether HCV Tx poses the same risk to men as it does to women. The protocol consisted of prospective screening of serum TSH levels every 12 weeks in 225 HCV-infected men during therapy with interferon- 2b (3 million U SC 3 times per week) and ribavirin (1 to 1.2 g orally once daily) for 24 to 48 weeks. Overt hypothyroidism was defined as a serum TSH level greater than 5.5 mIU/L with low concentrations of serum thyroxine and triiodothyronine; subclinical hypothyroidism was defined as a serum TSH level greater than 5.5 mIU/L with normal levels of serum thyroxine and triiodothyronine.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,22,Overt or subclinical thyroid disease developed in 6.7% and 4% of the participants, respectively. Antithyroid antibodies were detected in pts with overt hypothyroidism, and antibodies against the TSH receptor were detected in two thirds of pts with overt hyperthyroidism. After therapy with interferon- 2b and ribavirin was discontinued, 10 of 12 overtly hypothyroid pts, 2 of 3 overtly hyperthyroid pts, and all 9 pts with subclinical thyroid disease became euthyroid.,Arch intern Med. 2004;164:2371-6.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,23,The authors concluded that periodic screening for thyroid disease is indicated for men undergoing therapy for HCV infection. Thyroid dysfunction is readily managed once detected and treated. Abnormal thyroid function after interferon therapy has been a recognized entity for some time, and this study confirms that dysfunction also occurs with combined therapy with interferon and ribavirin. The risk is greatest in pts with a family history of autoimmune thyroid disease (either Hashimoto thyroiditis or Graves disease), and such individuals should be regularly screened for thyroid dysfunction both before and during therapy.,Arch intern Med. 2004;164:2371-6.,业精于勤荒于嬉 行成于思毁于随 【医学生物PPT，欢迎收藏分享】豆丁网友,24,Combination Therapy with Thyroxine and Triiodothyronine Offers No Advantage over Tx with Thyroxine Alone (Clin Endocrinol (Oxf). 2004;60:750-7. ),Some hypoth