Long-term ventilation for patients with Duchenne muscular dystrophy : physicians' beliefs and practices

STUDY OBJECTIVES: Although long-term ventilation (LTV) has been shown to extend the lives of individuals with Duchenne muscular dystrophy (DMD), initiating LTV is still considered controversial. The purpose of the study was to describe the LTV-related attitudes and practices of Canadian physicians who follow up patients with DMD. DESIGN: The study consisted of a mail questionnaire supplemented by face-to-face interviews. PARTICIPANTS: Forty-five physicians who follow up patients with DMD through Canadian neuromuscular clinics. MEASUREMENTS: A mail questionnaire of 66 closed-ended questions related to practice and attitudes was completed by all respondents. Qualitative semistructured interviews were conducted with six volunteer physicians, and were audiotaped and transcribed. RESULTS: The results indicated that 25.0% of physicians do not discuss LTV with all of their DMD patients. The most frequently cited reason for advising against LTV was poor patient quality of life (52.6%). Three themes emerged from the qualitative data: mentioning and discussing LTV are discrete events with different purposes, nighttime and full-time LTV decisions are approached differently, and physicians modify their discussions to influence outcome. CONCLUSIONS: The study demonstrated considerable agreement among the physicians regarding disclosure practices. Concerns are raised by the number of physicians who do not disclose to all patients and families and the role of quality-of-life judgments in decision making. It is suggested that because of their subjective nature, quality-of-life judgments should not be made without the participation of the patient and family, and that an initial disclosure is the minimum requirement of informed consent/decision making.     

Validation of a novel method for determination of low-density lipoprotein cholesterol levels in Indian patients with type 2 diabetes

Background and aimsLDL-cholesterol (LDL-C), being the primary predictor of cardiovascular disease in Type 2 diabetes (T2D), is associated with cardiovascular risk stratification and requires to be estimated with better accuracy with minimal bias. Different formulae have been devised to calculate the LDL-C from the measured lipid profile parameters.MethodsIn this analytical cross-sectional study, a total of 150 patients with T2D were studied, and blood samples were subjected for lipid profile analysis at the Central Biochemistry laboratory. Different formulae assessed calculated LDL-C.ResultsWe observed that all formulae, except Ahmadi, underestimated the LDL-C compared to direct assay. A significant difference was observed between all calculated LDL-C and directly measured LDL-C. On linear regression analysis, the newer formula Martin's has a better approximation with direct assay (slope: 0.9708) than Friedewald (slope: 0.9477). Similarly, Martin's formula exhibited lesser bias (?13.56) in calculating LDL-C in patients with T2D compared with Friedewald's formula.ConclusionsThe study demonstrated that in patients with T2D, all formulae except Ahmadi significantly underestimated the LDL-C when compared with the direct assay. The newer Martin's formula appeared to more precisely calculate LDL-C in T2D when compared with the traditional Friedewald's formula.     

Higher HDL cholesterol levels are associated with a lower incidence of chronic kidney disease in patients with type 2 diabetes

Background and aimsType 2 diabetes is one of the most important risk factor for the development of chronic kidney disease (CKD). Recently, it has been shown that lower high-density lipoprotein cholesterol (HDL-C) levels predicted the development of microalbuminuria in type 2 diabetic individuals. We have prospectively assessed the effects of plasma HDL-C levels on the incidence of CKD in a large cohort of type 2 diabetic patients.Methods and resultsWe followed 1987 type 2 diabetic outpatients with normal or near-normal kidney function at baseline for 5 years for the occurrence of incident CKD defined as glomerular filtration rate ≤ 60 mL/min/1.73 m² (as estimated by the abbreviated Modified Diet and Renal Disease Study equation). Cox proportional hazards models were used to examine the independent relationship between plasma HDL-C levels and incident CKD. During a median follow-up of 5 years, 11.8% (n = 234) of participants developed incident CKD. In multivariate regression analysis, higher HDL-C levels were associated with a lower risk of incident CKD (multiple-adjusted hazard ratio 0.76; 95% coefficient intervals 0.61–0.96; p = 0.025) independently of age, gender, body mass index, hypertension, smoking history, diabetes duration, hemoglobin A1c, plasma triglycerides, LDL-cholesterol, presence of diabetic retinopathy, baseline albuminuria, and current use of medications (anti-hypertensive, anti-platelet, lipid-lowering and hypoglycemic drugs).ConclusionsHigher plasma levels of HDL-C are associated with a lower risk of incident CKD in a large cohort of type 2 diabetic adults independently of numerous confounding factors.     

Predicting diabetes distress in patients with Type 2 diabetes: a longitudinal study

Aims Diabetes distress (DD) is a condition distinct from depression that is related to diabetes outcomes. In those without distress initially, little is known about what indicators place patients at risk for subsequent distress over time. Methods From a community‐based, three‐wave, 18‐month study of Type 2 diabetic patients (n = 506), we identified patients with no DD at T1 who displayed DD at T2, T3 or both (n = 57). Using logistic regression with full and trimmed models, we compared them with patients with no DD at all three time points (n = 275) on three blocks of variables: patient characteristics (demographics, depression, extra‐disease stress), biological (HbA_1c, body mass index, comorbidities, complications, blood pressure, non‐high‐density lipoprotein‐cholesterol), and behavioural variables (diet, exercise). Selected interactions with stress and major depressive disorder (MDD) were explored. Results The odds of becoming distressed over time were higher for being female, previously having had MDD, experiencing more negative events or more chronic stress, having more complications, and having poor diet and low exercise. Negative life events increased the negative effects of both high HbA_1c and high complications on the emergence of distress over time. Conclusions We identified a list of significant, independent direct and interactive predictors of high DD that can be used for patient screening to identify this high‐risk patient cohort. Given the impact of high DD on diabetes behavioural and biological indicators, the findings suggest the usefulness of regularly appraising both current life and disease‐related stressors in clinical care.     

Circulating homocysteine levels in patients with type 2 diabetes mellitus

Background and aimPrevious studies have shown conflicting results regarding circulating homocysteine levels in patients with type 2 diabetes.Methods and resultsThis observational study included 2121 patients with angiographically proven coronary artery disease (507 patients with type 2 diabetes and 1614 patients without diabetes). Circulating homocysteine levels, methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, renal function, presence of coronary artery disease (CAD) diagnosed by coronary angiography, and circulating folate and vitamin B₁₂ status were assessed. Plasma homocysteine levels [median (25th; 75th percentile)] were significantly higher in patients with diabetes than in those without [12.4 μmol/L (9.9 μmol/L; 15.9 μmol/L) versus 11.7 μmol/L (9.6 μmol/L; 14.5 μmol/L), P = 0.011]. Diabetes affected homocysteine levels only in patients with a glomerular filtration rate <90 mL/min [13.0 μmol/L (10.5 μmol/L; 16.7 μmol/L) in patients with diabetes versus 12.2 μmol/L (10.1 μmol/L; 15.2 μmol/L) in patients without diabetes, P = 0.006] but not in those with a glomerular filtration rate ≥90 mL/min [10.1 μmol/L (8.1 μmol/L; 12.4 μmol/L) versus 10.2 μmol/L (8.8 μmol/L; 12.3 μmol/L), P = 0.267]. Multivariable analysis did not show an independent association between diabetes and homocysteine level (P = 0.342).ConclusionCirculating homocysteine levels are increased in patients with type 2 diabetes compared with non-diabetic patients due to a more diabetes-associated adverse risk profile rather than to diabetes itself.     

老年2型糖尿患者的综合评估和管理研究进展

针对老年2型糖尿病（T2DM）高龄、病程长、合并症多的特点,回顾目前老年糖尿患者合并多种老年综合征的流行病学资料,探讨老年糖尿病患者的适宜血糖管理目标,并对目前采用老年综合评估方法综合管理老年T2DM患者的研究文献进行综述,以寻找开展老年糖尿患者综合评估管理工作的方向。     

Circulating cholesterol as a modulator of risk for renal injury in patients with type 2 diabetes

Amelioration of albuminuria may be related to specific constellations of risk factors including race and dyslipidaemia. Circulating cholesterol could mitigate the beneficial effect of antihypertensive therapy. We assessed whether cholesterol affected the remission of urinary albumin in patients with type 2 diabetes of white, Caucasian and non-white origin. We studied 100 patients (African and Asian: n=57 and Caucasian: n=43) with type 2 diabetes and newly diagnosed microalbuminuria who received intensified and structured care for a median (IQ range) of 41 (32-48) months. Microalbuminuria remitted in 20% and progressed in 12% of patients. In those with uncontrolled systolic hypertension (>140 mmHg) systolic blood pressure fell by a mean (95% CI) of -9.4 (-3.8 to -15.11)mmHg; p=0.002. The change in urinary albumin excretion with time varied inversely with baseline systolic blood pressure (r=-0.25; p=0.04). At 3 years follow-up the decrement in blood pressure was significant for those patients in the regression group (-19.6[16.8]mmHg; p=0.005). In patients of African origin, systolic blood pressure was higher than in the other groups and correlated with cholesterol concentrations (r=0.44; p=0.04). Baseline systolic blood pressure and total cholesterol (odds ratio [95%CI]) were independent determinants of remission and progression of microalbuminuria (1.04[1.006-1.064]; p=0.02 and 1.75[1.03-2.95]; p=0.04). Patients with higher total cholesterol and baseline urinary albumin excretion were less likely to go into remission. Blood pressure correlated with cholesterol concentrations in patients of African origin. Specific cholesterol lowering strategies may benefit certain patients groups at high risk of renal disease.     

Pioglitazone and reductions in post-challenge glucose levels in patients with type 2 diabetes

AIM: Pioglitazone (PIO) has been shown to decrease insulin resistance in patients with type 2 diabetes, resulting in lowered blood glucose concentrations, lowered plasma insulin levels and lowered haemoglobin A1C (A1C) values. Postprandial glucose control has been recently recognized as an important target for reducing overall glycemic burden in patients with type 2 diabetes. Some authors assert that reductions in postprandial glucose levels may lead to a decrease in cardiovascular risk, one of the major complications associated with diabetes. METHODS: Data were analysed from a 26-week PIO monotherapy study of 88 patients who underwent a 3-h oral glucose tolerance test (75 g dose) at baseline and last measurement. Change from baseline in area under the curve (AUC) values and hourly glucose concentrations were calculated and analysed at both time points for four medication groups: placebo group and PIO 15, 30 and 45 mg groups. Changes from baseline in fasting plasma glucose (FPG) and A1C also were reported. RESULTS: Glucose AUC was significantly (p < 0.05) different from baseline at 15, 30 and 45 mg doses of PIO. In addition, when compared to placebo, PIO (15, 30 and 45 mg) significantly decreased post-challenge blood glucose AUC (p < 0.05). The mean hourly blood glucose levels at last measurement for PIO 15, 30 and 45 mg all were significantly lower (p < 0.05) than placebo at all four time points. In addition, PIO significantly (p < 0.05) reduced FPG and A1C from baseline to last measurement in a dose-related fashion. CONCLUSIONS: PIO significantly reduced post-challenge glucose levels following an oral glucose challenge, leading to improvements in overall glycemic control. Postprandial glucose lowering is one of several metabolic effects of PIO in addition to decreasing insulin resistance and improving some lipids components. Whether these combined metabolic effects can lead to cardiovascular risk reductions may be confirmed by the pending results of cardiovascular outcomes studies with PIO.     

利拉鲁肽对2型糖尿病患者血浆网膜素影响的研究

目的 探讨T2DM患者血浆网膜素水平的变化及利拉鲁肽治疗对网膜素水平的影响.方法 采用酶联免疫法测定T2DM患者及正常人血浆网膜素水平,分析血浆网膜素水平与BMI、WHR、胰岛素抵抗指数(HOMA-IR)、胰岛β细胞分泌指数(HOMA-IS)、FFA等的关系,观察利拉鲁肽治疗前后T2DM患者血浆网膜素水平的变化. 结果 T2DM患者血浆网膜素水平明显低于正常人[(19.3±3.9)vs(26.4±6.0) μg/L,P＜0.01].T2DM患者血浆网膜素水平与FIns、HOMA-IR呈负相关(r=-0.41,P＜0.05和r=-0.56,P＜0.01).T2DM患者经利拉鲁肽治疗后WHR、BMI、FPG、2hPG和HbA1c均显著降低(P均＜0.01),而HOMA-IS则显著增高(P＜0.01),空腹血浆网膜素水平也显著增高[(19.3±3.9)vs(21.2±3.8)μg/L,P＜0.01]. 结论 利拉鲁肽能有效改善T2DM患者糖代谢和IS,同时升高血浆网膜素水平.     

Nonoccupational postexposure HIV prevention: emergency physicians' current practices, attitudes, and beliefs

STUDY OBJECTIVE: We surveyed emergency physicians to determine current practices, knowledge, attitudes, and beliefs regarding nonoccupational postexposure prevention practices. METHODS: Two thousand randomly selected practicing emergency physicians from the American College of Emergency Physicians' national database and all graduating emergency medicine residents in 2000 were surveyed. Knowledge, role responsibility, self-efficacy, and attitudes and beliefs were measured and composite scores developed. Differences in responses between supporters and nonsupporters were compared for each category. RESULTS: Eight hundred eighty-nine responded, representing 60% (67/113) of emergency medicine residencies, 32% (347/1095) of emergency medicine residents, and 27% (542/2000) of emergency physicians. Responders recommend nonoccupational postexposure prevention for sexual assault (35%), unintentional needle stick (25%), and, rarely (<15%), for unsafe sexual practices and injection drug use. Knowledge of Centers for Disease Control and Prevention recommendations or the time when treatment may be most beneficial is poor (15.5% and 13.7%, respectively). Most agree their role includes providing nonoccupational postexposure prevention drugs and referring patients for counseling (76.5% and 75.6%, respectively). Confidence in assessing need for nonoccupational postexposure prevention varied with exposure type (sexual assault [61.6%], unintentional needle stick [54.8%], unsafe sexual practices [40.4%], and injection drug use [49.7%]). Supporters of nonoccupational postexposure prevention (64.1%) are more likely to have nonoccupational postexposure prevention available (69.3% versus 42.9%; 95% confidence interval [CI] 19.7 to 33.1), written protocols (42.5% versus 33.0%; 95% CI 2.8 to 16.2), and higher mean composite scores than nonsupporters in all categories: knowledge, self-efficacy, role responsibility, and attitudes. CONCLUSION: Most emergency physicians surveyed agree that offering nonoccupational postexposure prevention is feasible and within their role responsibility. Establishing nonoccupational postexposure prevention protocols and providing educational programs are important first steps in changing practice.     

Effect of pioglitazone on blood proinsulin levels in patients with type 2 diabetes mellitus

The objective of this study was to clarify the influence of pioglitazone (Pio) on proinsulin (PI) in patients with type 2 diabetes mellitus. The subjects were 55 patients with type 2 diabetes. Among them, 18, 18, and 19 patients were respectively treated with Pio alone (group P), gliclazide (Gli) alone (group G), or Pio plus Gli (group PG) for 12 weeks. Fasting blood samples were obtained before and after treatment and were used to measure fasting plasma glucose (FPG), HbA1C, immunoreactive insulin (IRI), and PI. The levels of FPG, HbA1C, and IRI showed a significant decrease after treatment with Pio in groups P and PG. Treatment with Pio also caused PI to decrease significantly (group P: from 24.7 +/- 12.9 (mean +/- SD) to 14.0 +/- 6.2 pmol/L, p < 0.01, group PG: from 24.3 +/- 11.3 to 14.4 +/- 6.5 pmol/L, p < 0.01). In group G, treatment with Gli caused FPG and HbA1C to decrease significantly, but PI showed no change (21.5 +/- 12.3 to 21.6 +/- 10.4 pmol/L, p = n.s.). In patients with type 2 diabetes, treatment with Pio achieved an improvement of glycemic control and reduced the load on the pancreatic beta cells.     

Effects of pioglitazone on serum fetuin-A levels in patients with type 2 diabetes mellitus

Fetuin-A (α2-Heremans-Schmid glycoprotein), a circulating glycoprotein, can inhibit insulin signaling both in vivo and in vitro. Recently, we and another independent group have shown that fetuin-A is positively associated with insulin resistance in humans. Furthermore, it has been reported that higher fetuin-A levels are associated with metabolic syndrome and atherogenic lipid profiles. These data suggest that fetuin-A might be a regulator of insulin resistance and/or metabolic syndrome. However, it is not clear how fetuin-A levels are regulated. To address this, we investigated the effects of representative insulin-sensitizing therapies such as pioglitazone, metformin, and aerobic exercise on fetuin-A levels. Twenty-seven patients with type 2 diabetes mellitus were divided into pioglitazone-treated (Pio), metformin-treated (Met), and exercise-treated (Ex) groups. Ten patients in the Pio group and 9 patients in the Met group took 15 or 30 mg/d pioglitazone or 500 or 750 mg/d metformin, respectively, for 6 months. Eight patients in the Ex group underwent a 3-month aerobic exercise program. Serum fetuin-A levels were measured before and after each intervention. Intervention significantly decreased hemoglobin A_1c in all groups. After treatment, serum fetuin-A levels significantly decreased in the Pio group (291.2 ± 57.7 to 253.1 ± 43.9 μg/mL, P = .006), whereas there were no changes in serum fetuin-A after intervention in either the Met or the Ex groups. We hypothesize that pioglitazone could partially ameliorate insulin resistance via modulating fetuin-A levels.     

Effect of sitagliptin therapy on postprandial lipoprotein levels in patients with type 2 diabetes

Aim: Recent studies indicate that type 2 diabetes is associated with an increased secretion of both hepatic and intestinal lipoproteins, leading to the accumulation of atherogenic triglyceride (TG)‐rich lipoproteins. Sitagliptin is a selective inhibitor of dipeptidyl peptidase‐4 that has been shown to reduce fasting and postprandial glucose levels in patients with type 2 diabetes presumably through incretin hormone‐mediated improvements in islet function. The objective of the present study is to examine the effects of treatment with sitagliptin on postprandial lipid and incretin hormone levels as well as glucose homeostasis in patients with type 2 diabetes. Methods: Thirty‐six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m²) were recruited in this double‐blind cross‐over study using sitagliptin 100 mg/day or placebo for a 6‐week period each, with a 4‐week washout period between the two phases. At the end of each phase of treatment, patients underwent an oral lipid tolerance test providing 35 g of fat per m² of body surface area and blood samples were taken over an 8‐h period. Results: Sitagliptin therapy significantly decreased the postprandial area under the curves (AUCs) for plasma apolipoprotein (apo)B (?5.1%, p = 0.002), apoB‐48 (?7.8%, p = 0.03), TG (?9.4%, p = 0.006), very low‐density lipoprotein (VLDL)‐cholesterol (?9.3%, p = 0.001), free fatty acids (FFAs) (?7.6%, p = 0.005) and glucose (?9.7%, p < 0.0001). Furthermore, the postprandial AUCs for plasma intact glucagon‐like peptide‐1 (+67.8%, p < 0.0001) and glucose‐dependent insulinotropic polypeptide (+67.3%, p < 0.0001) were significantly increased following treatment with sitagliptin, whereas the AUC for plasma glucagon was reduced by ?9.7% (p = 0.001) with no significant changes in the AUCs for plasma insulin and C‐peptide. Sitagliptin therapy also improved homeostasis model assessment (HOMA) index for insulin resistance (?14.6%, p = 0.01) and β‐cell function (+32.3%, p = 0.007). Conclusions: Treatment with sitagliptin for 6 weeks reduced postprandial plasma levels of TG‐rich lipoproteins of both intestinal and hepatic origin, most likely by increasing incretin hormone levels, reducing circulating plasma FFA concentrations and improving insulin sensitivity and β‐cell function.     

2型糖尿病家系非糖尿病正常体重一级亲属脂联素水平5年随访

目的探讨2型糖尿病患者非糖尿病正常体重一级亲属脂联素水平变化及脂联素与胰岛素敏感性和颈动脉内膜中层厚度(IMT)之间的关系.方法入选2型糖尿病非糖尿病正常体重一级亲属53名和对照组37名,入组时检测了脂联素、血脂、血糖、血压及空腹胰岛素水平.用高频B超检测IMT及内皮依赖性血管舒张功能(EDVD).采用稳态模式(HOMA)评价胰岛素抵抗(HOMA-IR)和评价胰岛β细胞功能(HOMA-β).一级亲属组29名和对照组20名完成了5年随访.结果基线时一级亲属组血浆脂联素水平明显低于对照组[(10.06±5.79)对(14.43±7.91)mg/L,P<0.05].5年后一级亲属组脂联素水平降低24.0%(P<0.05),对照组脂联素水平降低36.7%(P<0.05).一级亲属组脂联素与腰臀比(r=-0.397)、空腹血糖(r=-0.373)、IMT(r=-0.372)和HOMA-IR(r=-0.40)负相关(均P<0.05).校正相关因素后,多元逐步回归分析显示一级亲属组脂联素与年龄,高密度脂蛋白胆固醇(HDL-C),IMT独立相关.对照组脂联素与低密度脂蛋白胆周醇(LDL-C)和IMT独立相关.结论 5年后一级亲属组和对照组脂联素水平均明显降低,脂联素降低可能与IMT增加相关.     

Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction

Background:

Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1.

Methods:

Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m⁻², age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day.

Results:

Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03).

Conclusion:

Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism.     

Impact of obesity on annual medical expenditures and diabetes care in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

Diabetes and obesity are important health and economic concerns. We investigated the influence of obesity on diabetes control, the annual medical expenditures and medications in Japanese patients with type 2 diabetes who were relatively lean in comparison with those in Western countries.

Materials and Methods

A total of 402 Japanese patients with type 2 diabetes were enrolled and their annual medical expenditures investigated. Obesity was defined as body mass index ≥25 kg/m², according to the obesity classifications from the Japan Society for the Study of Obesity.

Results

A total of 165 patients (41.0%) were classified as obese. The obese group was younger, had poor glycemic control and higher frequency of hypertension than the non‐obese group. The median total annual medical expenditures for all participants was ¥269,333 (interquartile range ¥169,664–437,437), which was equivalent to approximately $US2,450. The annual medical expenditure was significantly higher in patients with obesity than in non‐obese patients (P < 0.001). This difference was mainly attributed to the annual expenditures for medication and hospitalization. In particular, the medication expenditures and the average number of drug classes for hyperglycemia and hypertension were significantly higher in the obese group.

Conclusions

Japanese patients with type 2 diabetes and obesity had higher annual medical expenditures and a larger number of medications, but their diabetes control care was insufficient in comparison with those without obesity. Further studies are required to assess the effect of reducing bodyweight on diabetes control and costs.