Body weight changes with beta-blocker use: results from GEMINI

Purpose

Patients with type 2 diabetes are commonly overweight, which can contribute to poor cardiovascular outcomes. β-blockers may promote weight gain, or hamper weight loss, and are a concern in high-risk patients. The current analysis of the Glycemic Effect in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial evaluates the effects of carvedilol and metoprolol tartrate on weight gain in patients with type 2 diabetes and hypertension.

Methods

This prespecified secondary analysis of the GEMINI study (n=1106) evaluated change in body weight after 5 months.

Results

Mean (±SE) baseline weights were 97.5 (±20.1) kg for carvedilol and 96.6 (±20.1) kg for metoprolol tartrate. Treatment difference (c vs m) in mean (±SE) weight change from baseline was −1.02 (±0.21) kg (95% confidence interval [CI], −1.43 to −0.60; P <.001). Patients taking metoprolol had a significant mean (±SE) weight gain of 1.19 (±0.16) kg (P <.001); patients taking carvedilol did not (0.17 [±0.19] kg; P =.36). Metoprolol tartrate-treated patients with body mass index (BMI) >30 kg/m² had a statistically significant greater weight gain than comparable carvedilol-treated patients. Treatment differences (c vs m) in the obese (BMI >30 kg/m²) and morbidly obese groups (BMI >40 kg/m²) were −0.90 kg (95% CI, −1.5 to −0.3; P =.002) and −1.84 kg (95% CI, −2.9 to −0.8; P =.001), respectively. Pairwise correlation analyses revealed no significant associations between weight change and change in HbA_1c, HOMA-IR, or blood pressure.

Conclusions

Metoprolol tartrate was associated with increased weight gain compared to carvedilol; weight gain was most pronounced in subjects with hypertension and diabetes who were not taking insulin therapy.     

神经症状/神经缺陷评分与神经传导速度诊断糖尿病周围神经病变的相关性

目的 研究神经症状/神经缺陷评分（NSS/NDS）与神经传导速度（NCV）在诊断糖尿病周围神经病变（DPN）中的相关性,并探讨NSS/NDS的临床使用价值.方法 以679例同时测定了NSS/NDS评分和NCV的2型糖尿病患者为研究对象,男性404例,女性275例,平均年龄（59±ll）岁.以NCV作为诊断DPN的金标准,分析NSS/NDS评分诊断DPN的敏感度、特异度、阳性预测值、阴性预测值、准确度、约登指数、Kappa值（一致性）及相关性等.采用Spearman相关和多因素logistic逐步回归进行相关性分析.结果 NSS/NDS评分诊断DPN的敏感度、特异度、阳性预测值、阴性预测值、准确度、约登指数、一致性及相关性分别为68.0％、77.2％、86.5％、53.5％、71.0％、45.2％、0.405、0.424.当NSS≥5分或NDS≥6分时,患者有较高的NCV异常率（77.8％ ～ 100％）.NSS、NDS评分与NCV均呈正相关（r=0.292、0.358,均P＜0.01）,患者神经症状或体征越严重,越容易引起NCV的减慢.Logistic回归分析显示NSS/NDS评分诊断DPN的危险因素是病程、年龄和UAlb/Cr[比值比（OR）=1.085、1.051、1.002,均P＜0.01].与NCV诊断DPN的危险因素相关性较好.结论 NSS/NDS评分与NCV诊断DPN有相关性,尤其是神经症状、神经缺陷严重时相关性更好.NSS/NDS评分操作简单快速,方便有效,可在临床中作为DPN的筛查.     

Differential effect of beta-blocker therapy on insulin resistance as a function of insulin sensitizer use: results from GEMINI.

AIMS: To determine whether the beneficial effects of carvedilol on insulin resistance (IR) are affected by the concomitant use of insulin sensitizers [thiazolidinediones (TZDs) and metformin]. METHODS: Changes in HbA1c and homeostasis model assessment-insulin resistance (HOMA-IR) were assessed over 5 months, comparing carvedilol with metoprolol tartrate according to insulin sensitizer (TZDs and metformin) use. RESULTS: In TZD/metformin users, carvedilol patients showed a 5.4% decrease [95% confidence interval (CI) -11.9, 1.6; P = 0.13] and metoprolol tartrate patients showed a 2.8% decrease (95% CI -8.5, 3.2; P = 0.35) in HOMA-IR. The -2.6% difference between treatments was not significant (95% CI -10.7, 6.2; P = 0.55). In contrast, those not taking TZD/metformin experienced a 13.2% increase in HOMA-IR on metoprolol tartrate (95% CI 3.2, 24.1; P < 0.01) and a 4.8% decrease in HOMA-IR on carvedilol (95% CI -14.6, 6.0; P = 0.37), with a significant treatment difference of -15.9% favouring carvedilol (95% CI -26.6, -3.6; P = 0.01). There was no significant treatment interaction for the use of TZD/metformin and HbA1c. A statistically significant treatment difference was observed for HbA1c after 5 months favouring carvedilol after adjusting for insulin sensitizer use (-0.11%, 95% CI -0.214, -0.009; P = 0.03). CONCLUSIONS: In patients with diabetes and hypertension not taking insulin sensitizers, the use of metoprolol tartrate resulted in a worsening of insulin resistance, an effect not seen with carvedilol. However, in TZD/metformin users the difference between the beta-blockers was not statistically significant.     

Effect of a gastro-protective agent, rebamipide, on symptom improvement in patients with functional dyspepsia: a double-blind placebo-controlled study in Japan

BACKGROUND AND AIM: Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis, there has been no well-controlled study of functional dyspepsia. The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia. METHODS: In a double-blinded, randomized, placebo-controlled, single-center study, 81 patients with functional dyspepsia were recruited and treated with rebamipide (100 mg, t.i.d.) or placebo for 4 weeks. Symptoms were assessed at baseline and at the end of the study period by a symptom questionnaire. Quality of life was evaluated by the QPD 32. RESULTS: Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment. Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment, and the mean changes in overall symptoms were not significantly different between the groups. However, the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items, which were bloating, belching, and pain or discomfort that was relieved after a meal. Regarding quality of life, social restriction and pain intensity were significantly improved in the rebamipide treatment group in per-protocol analysis (P = 0.048 and P = 0.031, respectively). CONCLUSIONS: Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks' treatment, it may partially improve the symptoms. It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia.     

Comparing diabetes due to diseases of the exocrine pancreas to type 1 and type 2 diabetes using propensity score matching

ObjectiveTo estimate the prevalence of diabetes due to diseases of the exocrine pancreas (DEP) using data of the multicentre diabetes patient follow-up registry. Moreover, we aimed at comparing individuals with diabetes due to DEP to individuals with type 1 and type 2 diabetes.MethodsIndividuals with DEP, type 1 or type 2 diabetes ≥18 years of age were studied. We aggregated the most recent treatment year per patient and used propensity scores to match diabetes due to DEP to type 1 and type 2 diabetes. Matching was conducted one-to-one with sex, age, diabetes duration, migration background and the German index of socioeconomic deprivation as covariates.ResultsWe identified 7,093 (1.6%) individuals with diabetes due to DEP. In the matched cohort DEP-type 1 diabetes we observed a similar daily insulin dose (0.62 IU/kg (95% confidence interval:0.60–0.63), 0.60 IU/kg (0.58–0.62)) and significant differences regarding microvascular (41.0% (39.7–42.2), 45.3% (44.0–46.6)), and macrovascular disease (16.6% (15.7–17.6), 14.7% (13.8–15.6)). HbA1c (8.2% (8.1–8.3), 7.9% (7.8–8.0)), daily insulin dose (0.60 IU/kg (0.58–0.62), 0.56 IU/kg (0.54–0.58)) and event rates of severe hypoglycemia (23.9 events/100 PY (21.4–26.8), (9.5 events/100 PY (8.0–11.2)) were significantly higher in individuals with diabetes due to DEP compared to type 2 diabetes.ConclusionsUsing registry data, rare diabetes types such as diabetes due to DEP can be studied with a significant sample size. Our study identified differences and similarities between adult individuals with DEP related diabetes and type 1 or type 2 diabetes.     

Symptom scoring systems to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom score.

AIMS: To provide one of the diagnostic categories for distal diabetic polyneuropathy,several symptom scoring systems are available, which are often extensive and lack in validation. We validated a new four-item Diabetic Neuropathy Symptom (DNS) score for diagnosing distal diabetic polyneuropathy. METHODS: We compared score characteristics of the generally accepted Neuropathy Symptom Score (NSS) with the DNS score, and tested construct validity,predictive value and reproducibility with the Diabetic Neuropathy Examination score, Semmes-Weinstein monofilaments and Vibration Perception Threshold(clinical standards) in 73 patients with diabetes (24 Type 1, 49 Type 2;43 male/30 female; mean age 57 years (19-90);mean diabetes duration 15 years (1-43)). RESULTS: Correlation between NSS and DNS score was high (Spearman r= 0.88). Patient scores were more differentiated on the DNS score. The relation of the NSS and DNS scores, respectively, with clinical standards was good (Spearman r= 0.21-0.60). Reproducibility of the DNS score was high (Cohen weighted kappa 0.78-0.95). The DNS score was easier to perform in clinical practice. CONCLUSIONS: The DNS is validated, fast and easy to perform, with a high predictive value when screening for diabetic polyneuropathy.     

Hyperglycaemia, hypoglycaemia, and blood glucose control in diabetes: symptom perceptions and treatment strategies.

Recent research has suggested that patients with Type 1 diabetes who are in chronically poor blood glucose control perceive hyperglycaemia differently from those who are in good control. To extend these observations 181 insulin-treated patients with Type 1 or Type 2 diabetes were studied. Patients completed a self-report questionnaire which included items concerning feelings about high and low blood glucose levels and strategies for maintaining blood glucose control. Glycosylated haemoglobin levels were also measured. We hypothesized that level of blood glucose control would: (1) be associated with perceptions of hyperglycaemia and treatment strategies for managing hyperglycaemia and (2) not be associated with perceptions and strategies concerning hypoglycaemia. In comparison with those in 'acceptable' or 'poor' blood glucose control, those in 'good' control perceived symptoms of hyperglycaemia at lower blood glucose levels (p less than 0.001) and felt physically best at lower blood glucose levels (p less than 0.001). They, also began treatment for hyperglycaemia at lower glucose levels (p less than 0.05), set lower minimal (p less than 0.001) and maximal (p less than 0.001) glucose levels as treatment goals, and tested their blood glucose levels more frequently (p less than 0.05). Among Type 1 diabetic patients, those in 'good' control reported experiencing hypoglycaemia at lower glucose levels than those in 'acceptable' or 'poor' control (p less than 0.05). No differences in treatment strategies of hypoglycaemic symptoms were apparent. This study suggests an influence of patients' perceptions of symptoms and treatment in self-care of diabetes.     

Treating diabetes with islet transplantation: Lessons from the past decade in Lille

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit–risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.     

The development of the GERD-HRQL symptom severity instrument

The Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) instrument was introduced approximately 10 years ago to provide a quantitative method of measuring symptom severity in gastroesophageal reflux disease (GERD). Since that time the instrument has been used to assess treatment response to medication, endoscopic procedures, and surgery for GERD. However, the development of the instrument has progressed over the course of several years, and there is no one source which reviews this progress. The purpose of this article is to summarize the development and testing of the GERD-HRQL. The GERD-HRQL was initially developed to measure the typical symptoms of GERD. It was initially determined to have face validity and subsequent studies assessed its content validity, criterion validity, concurrent validity, predictive validity and construct validity. Reliability was determined by the test-retest method. Responsiveness was determined by the effects of treatment. This instrument is practical, with little administrative burden. There are few missing responses. Because there are 51 possible scores, the instrument has a high level of precision; and because of the response anchors, cannot have a floor effect, and only 4/372 patients reached the highest score of 50, implying little ceiling effect. The instrument has been translated into several languages, and appears valid, reliable and practical in each.     

Improvements in quality of life associated with insulin analogue therapies in people with type 2 diabetes: results from the A1chieve observational study

Aims

To determine the effects on quality of life after starting insulin with, or switching to, insulin analogue therapies in the 24-week, prospective, non-interventional, observational A₁chieve study conducted across four continents in people with type 2 diabetes.

Methods

Health-related quality of life (HRQoL) was assessed at baseline and at 24 weeks by the validated EQ-5D questionnaire (visual analogue score [VAS] and five dimensions) in 66,726 people who had started using basal insulin detemir, mealtime insulin aspart (with or without a basal insulin) or biphasic insulin aspart 30.

Results

For the overall cohort, reported HRQoL increased significantly by 13.8 points from 63.4 points at baseline to 77.2 points at 24 weeks (p < 0.001) (scale 1-100, 100 = best health imaginable). Beginning or changing insulin was associated with a significant increase in HRQoL score (+15.0 points and +11.1 points, respectively), resulting in a similar score at 24 weeks in the two populations (77.8 and 75.9 points). Reported HRQoL also increased statistically significantly in people administering any insulin analogue regimen and across all regions, although there were some marked regional differences in reported HRQoL at baseline.

Conclusion

Compared with baseline scores, beginning insulin with, or switching to, insulin analogue therapies are associated with increased HRQoL.     

Quality of diabetes care predicts the development of cardiovascular events: results of the QuED study

Background and aimIn the context of the QuED Study we assessed whether a quality of care summary score was able to predict the development of cardiovascular (CV) events in patients with type 2 diabetes.Methods and resultsThe score was calculated using process and intermediate outcome indicators (HbA_1c, blood pressure, low-density lipoprotein cholesterol, microalbuminuria) and ranged from 0 to 40. Overall, 3235 patients were enrolled, of whom 492 developed a CV event after a median follow-up of 5 years. The incidence rate (per 1000 person-years) of CV events was 62.4 in patients with a score ≤10, 54.8 in those with a score between 15 and 20, and 39.8 in those with a score >20. In adjusted multilevel regression models, the risk to develop a CV event was 89% greater in patients with a score of ≤10 (rate ratio [RR] = 1.89; 95% confidence interval [CI] 1.43–2.50) and 43% higher in those with a score between 10 and 20 (RR = 1.43; 95% CI 1.14–1.79), as compared to those with a score >20. A difference between centers of 5 points in the mean quality score was associated with a difference of 16% in CV event risk (RR = 0.84; 95% CI 0.72–0.98).ConclusionOur study documented for the first time a close relationship between a score of quality of diabetes care and long-term outcomes.     

Psychosocial and cognitive multimorbidity and health-related quality of life and symptom burden in older adults with atrial fibrillation: The systematic assessment of geriatric elements in atrial fibrillation (SAGE-AF) cohort study

BackgroundDepression, anxiety, and cognitive impairments occur in up to 40 % of adults with AF and are associated with poorer health-related quality of life (HRQoL) and higher symptom burden. However, it is unknown how often these impairments co-occur, or multimorbidity, and how multimorbidity effects HRQoL and symptom burden.MethodsPatients with AF age ≥65 years with a CHA₂DS₂VASC risk score ≥ 2 and eligible for oral anticoagulation therapy were recruited from five clinics in a prospective cohort study. Participants completed validated measures of depression (PHQ9) and anxiety (GAD7), cognitive impairment (MoCA), and HRQOL and AF symptom burden (AFEQT). Multinomial logistic regression was used.ResultsParticipants (N = 1244, 49 % female) were on average 76 ± 7 years; 86 % were non-Hispanic white. Approximately 35 % of participants had 1 impairment, 17 % had 2 impairments and 8% had 3 impairments; 39 % had none of the 3 impairments examined. Compared to participants with no impairments, patients with 1, 2 and 3 impairments had higher odds of poor HRQoL (adjusted OR [AOR] = 1.77, 95 % CI 1.21, 2.60; AOR = 6.64, 95 % CI 4.43, 9.96; and AOR = 7.50, 95 % CI 4.40, 12.77, respectively) and those with 2 and 3 impairments had higher odds of high symptom burden (AOR = 3.69 95 % CI 2.22, 6.13; and AOR = 5.41 95 % CI 2.85, 10.26).ConclusionsPsychosocial/cognitive multimorbidity is common among older adults with AF and is associated with poor HRQoL and high symptom burden. Clinicians might consider incorporating psychosocial and cognitive screens into routine care as this may identify a high-risk population.     

A randomized, controlled trial to study the effect of exercise consultation on the promotion of physical activity in people with Type 2 diabetes: a pilot study.

AIM: To evaluate the effect of exercise consultation on promotion of physical activity in people with Type 2 diabetes. METHODS: Twenty-six sedentary people with Type 2 diabetes were randomly assigned to receive an exercise consultation and standard exercise information (experimental) or standard exercise information alone (control). Exercise consultation is a one-to-one discussion, based on the transtheoretical model, designed to educate, strengthen motivation and develop realistic strategies to promote physical activity. Changes from baseline at five weeks were assessed in (a) stage of exercise behaviour (b) physical activity levels (7-day recall questionnaire and an accelerometer) (c) quality of life (SF-36 Health Survey and 22-Item Well-Being Questionnaire). RESULTS: 82% (9/11) of participants receiving a consultation increased their stage of exercise behaviour compared to 33% (4/12) of controls (chi2 = 5.4, P = 0.02). Physical activity counts/week increased by 4% (1636 067/1696 191) in the experimental group and decreased by 9% (1560 960/1725 510) in controls. A significant difference was recorded for the change in activity counts per week from baseline to follow-up between the experimental and control group (98% CI = 60 673-710 827). The number of participants taking part in sport or leisure activity increased by 55% (6/11) in the experimental group and decreased by 6% (1/12) in controls. Positive changes were evident in the experimental group, compared to controls, in both quality of life questionnaires. CONCLUSION: Exercise consultation is more effective in stimulating exercise behaviour change in the short term than a standard exercise leaflet.     

Usefulness of the vibration perception thresholds measurement as a diagnostic method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2 diabetes cohort study

Aims

To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN).

Diabetes reversal: Update on current knowledge and proposal of prediction score parameters for diabetes remission

Background and aimThe field of diabetes reversal is continuously evolving. Strategies for implementing diabetes care towards diabetes reversal are still being worked out. We aim to analyse data from available literature to ascertain factors allowing patient centric dietary approach to achieve diabetes reversal in clinical practice.MethodsIn this exploratory review, an update on current knowledge is presented to delineate factors driving diabetes remission in an individual based on major studies in the field. This knowledge is then applied to subtypes of type 2 diabetes to optimise dietary approach for reversal of diabetes.Results and conclusionShorter duration of diabetes, lesser number of medicines needed to achieve euglycemia and 15 kg weight loss are common factors favouring diabetes remission in all major studies. A patient centric approach to diabetes reversal taking into account the recently described diabetes subtypes is being proposed to improve the proportion of patients achieving remission. We also propose the parameters of a novel diabetes remission prediction score, based on patient motivation, interaction with the care-team, level of diabetes self-care and the intent of the care-team.     

Evaluation of two screening methods for undiagnosed diabetes in China: An cost-effectiveness study

AimsTo evaluate the performance and cost-effectiveness of two screening methods to identify undiagnosed diabetes at primary care settings among a Chinese population.MethodsTwo screening methods using a fasting capillary glucose (FCG) test or a Chinese diabetes risk score (DRS) at primary care settings followed by diagnostic tests were compared. The performance of FCG and DRS was evaluated by using receiver operating characteristic (ROC) curve analysis. The main economic outcome measures were the total cost of screening per 1000 persons, proportion of undiagnosed diabetes detected, and cost per undiagnosed diabetes identified from the societal perspective.ResultsAmong all participants, 14.6% (1349/9232) had undiagnosed diabetes defined by fasting plasma glucose ≥7.0 mmol/l and/or 2 h plasma glucose ≥11.1 mmol/l and/or hemoglobin A1c ≥6.5%. At the optimal cutoff point of 6.1 mmol/l for FCG and 14 for DRS, the sensitivity was 65.1% and 65.8%, and specificity was 72.4% and 55.2%, respectively. The area under the ROC curve was 75.3% for FCG and 63.7% for DRS (P < 0.001). Based on the input costs, the total cost of screening 1000 persons was ¥64,000 ($9143) for FCG and ¥81,000 ($11,571) for DRS. The average cost per case identified was ¥674 ($96) for FCG at cutoff point of 6.1 mmol/l and ¥844 ($121) for DRS at score of 14. The incremental cost per case identified was ¥17,000 ($2429) for DRS compared to FCG. The dominance relations between strategies remained with the changed in sensitivity analysis.ConclusionsAs a first-line screening tool for undiagnosed diabetes, the FCG test performed better than the DRS in primary care settings in China. The non-invasive and layperson-oriented DRS was feasible and detected more cases but more expensive. No strategy has strong dominance that was both more effective and less costly. The favorable strategy will depend on if the purpose of the screening program is to identify more cases or to have lower cost per case.