Linagliptin plus metformin in patients with newly diagnosed type 2 diabetes and marked hyperglycemia

Objectives: Few studies of oral glucose-lowering drugs exist in newly diagnosed type 2 diabetes (T2D) patients with marked hyperglycemia, and insulin is often proposed as initial treatment. We evaluated the oral initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in this population.

Methods: We performed a pre-specified subgroup analysis of a randomized study in which newly diagnosed T2D patients with glycated hemoglobin A1c (HbA1c) 8.5%–12.0% received linagliptin/metformin or linagliptin monotherapy. Subgroups of baseline HbA1c, age, body-mass index (BMI), renal function, race, and ethnicity were evaluated, with efficacy measured by HbA1c change from baseline after 24 weeks.

Results: HbA1c reductions from baseline (mean 9.7%) at week 24 in the overall population were an adjusted mean ?2.81% ± 0.12% with linagliptin/metformin (n = 132) and ?2.02% ± 0.13% with linagliptin (n = 113); treatment difference ?0.79% (95% CI ?1.13 to ?0.46, P < 0.0001). In patients with baseline HbA1c ≥9.5%, HbA1c reduction was ?3.37% with linagliptin/metformin (n = 76) and ?2.53% with linagliptin (n = 61); difference ?0.84% (95% CI ?1.32 to ?0.35). In those with baseline HbA1c <9.5%, HbA1c reduction was ?2.08% with linagliptin/metformin (n = 56) and ?1.39% with linagliptin (n = 52); difference ?0.69% (95% CI ?1.23 to ?0.15). Changes in HbA1c and treatment differences between the linagliptin/metformin and linagliptin groups were of similar magnitudes to the overall population across patient subgroups based on age, BMI, renal function, and race. Drug-related adverse events occurred in 8.8% and 5.7% of linagliptin/metformin and linagliptin patients, respectively; no severe hypoglycemia occurred.

Conclusion: Linagliptin/metformin combination in newly diagnosed T2D patients with marked hyperglycemia was well tolerated and elicited substantial improvements in glycemic control regardless of baseline HbA1c, age, BMI, renal function, or race. Thus, newly diagnosed, markedly hyperglycemic patients may be effectively treated by combinations of oral agents.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT01512979     

Lorcaserin treatment allows for decreased number needed to treat for weight and glycemic parameters in week 12 responders with ≥5% weight loss

Objectives: Lorcaserin is a serotonin 2C receptor agonist approved for chronic weight management. This analysis explores the number of patients needed to be treated (NNT) with lorcaserin for one more patient to achieve weight loss and glycemic goals.

Methods: This is a post hoc analysis of three Phase 3 studies in adults with and without type 2 diabetes mellitus (T2DM) treated with lorcaserin 10 mg BID or placebo. NNT is reported for patients achieving ≥5% or ≥10% weight loss, achievement of either HbA1c <5.7% or FPG <100 mg/dL in patients with prediabetes, and reduction of HbA1c to <7% in patients with T2DM at Week 52.

Results: In the modified intention-to-treat (MITT) population, NNTs for ≥5% and ≥10% weight loss were 3.6 and 6.2 (without T2DM) and 4.3 and 7.5 (with T2DM); in Week 12 responders (≥5% weight loss at Week 12), NNTs were 1.7 and 2.6 (without T2DM) and 1.9 and 3.2 (with T2DM). In patients with prediabetes, NNTs to achieve HbA1c <5.7% were 9.9 (MITT) and 5.2 (Week 12 responders). In patients with T2DM, NNTs to achieve HbA1c <7% were 4.2 (MITT) and 2.3 (Week 12 responders).

Conclusion: In addition to weight management, lorcaserin improved glycemic control in patients with prediabetes and facilitated targeted HbA1c reduction in patients with T2DM, especially for those who achieved ≥5% weight loss by Week 12. Assessment of treatment response at Week 12 is a valuable tool to achieve efficient use of healthcare resources.

Clinical trial registration: www.clinicaltrials.gov identifiers are NCT00395135, NCT00603291, and NCT00603902     

Five-year observation of the relationship between body mass index and glycated hemoglobin in children with Type 1 diabetes mellitus

Abstract

Background: Poor metabolic control is a well-recognized risk factor for cardiovascular disease. However, the relationship between such factor as body weight and metabolic control in children with diabetes mellitus type 1 (DM1) is unclear. The aim of this study was to examine the relationships between body weight, age, metabolic control, sex, and form of insulin therapy in children with DM1.

Methods: This was a retrospective study of children with DM1 treated at one diabetes center for a minimum of 5?years since diagnosis.

Results: Median body mass index standard deviation score (BMI-SDS) increased annually (p?=?.0042) on average 0.08?±?0.27 per year throughout the observation. As well HbA1c and daily dose insulin increased annually (p?p?p?=?.01895). No correlation between BMI-SDS and metabolic control (HbA1c) was found (R?=?0.09, p?=?.60).

Conclusions: Body weight appears to be more affected by non-diabetic factors (e.g. irregular eating and sedentary lifestyle) than by the clinical course of diabetes. Metabolic control and body weight must be maintained in all children with DM1 (males and females) to reduce their future risk of cardiovascular disease.     

Utility of hemoglobin A1c for the identification of individuals with diabetes and prediabetes in a Chinese high risk population

Abstract Background. The aim of the study was to assess the utility of Hemoglobin A1c (HbA1c) to identify individuals with undiagnosed DM and prediabetes (preDM) in the high risk population of Chinese people. Methods. A total of 424 high risk individuals without known diabetes, who met at least three of the high risk factors for DM (hypertension, abnormal blood lipid, family history of DM and high BMI) were selected for this study, HbA1c, fasting plasma concentrations of glucose (FPG) and a 75 g oral glucose tolerance test (OGTT) were measured. The performance of HbA1c in relation to undiagnosed DM and preDM investigated through receiver operating characteristic (ROC) curves, the reference for DM and preDM, are according to the 2011 WHO-FPG/OGTT criteria and the appropriate cut-off points of HbA1c for DM and preDM were assessed. The properties of HbA1c diagnosing DM and preDM were also compared with that of the fasting plasma glucose (FPG). Results. It was shown that the AUC (area under the curve) of the ROC curve for HbA1c predicting undiagnosed DM was similar to that of FPG, and the cut-off point of HbA1c 6.2% was optimal for predicting DM, with a sensitivity of 66%, and a specificity of 91%. Furthermore, the cut-off point of HbA1c was 5.9% for preDM with a sensitivity of 70%, a specificity of 87%. Conclusion. Collectively, this study found that the measurement of HbA1c may be efficient to diagnosis undiagnosed both DM and preDM with the cut-off point of 6.2% and 5.9%, respectively.     

Are general practitioners characteristics associated with the quality of type 2 diabetes care in general practice? Results from the Norwegian ROSA4 study from 2014

Objective: To explore the associations between general practitioners (GPs) characteristics such as gender, specialist status, country of birth and country of graduation and the quality of care for patients with type 2 diabetes (T2DM).

Design: Cross-sectional survey.

Setting and subjects: The 277 GPs provided care for 10082 patients with T2DM in Norway in 2014. The GPs characteristics were self-reported: 55% were male, 68% were specialists in General Practice, 82% born in Norway and 87% had graduated in Western Europe. Of patients, 81% were born in Norway and 8% in South Asia. Data regarding diabetes care were obtained from electronic medical records and manually verified.

Main outcome measures: Performance of recommended screening procedures, prescribed medication and level of HbA1c, blood pressure and LDL-cholesterol stratified according to GPs characteristics, adjusted for patient and GP characteristics.

Result: Female GPs, specialists, GPs born in Norway and GPs who graduated in Western Europe performed recommended procedures more frequently than their counterparts. Specialists achieved lower mean HbA1c (7.14% vs. 7.25%, p?p?=?0.018) and lower mean systolic blood pressure (133.0?mmHg vs. 134.7?mmHg, p?p?Conclusion: Several quality indicators for type 2 diabetes care were better if the GPs were specialists in General Practice.

• Key Points

• Research on associations between General Practitioners (GPs) characteristics and quality of care for patients with type 2 diabetes is limited.

• Specialists in General Practice performed recommended procedures more frequently, achieved better HbA1c and blood pressure levels than non-specialists.

• GPs who graduated in Western Europe performed screening procedures more frequently and achieved lower diastolic blood pressure compared with their counterparts.

• There were few significant differences in the quality of care between GP groups according to their gender and country of birth.

     

Prevalence of comorbidity in primary care patients with type 2 diabetes and its association with elevated HbA1c: A cross-sectional study in Croatia

Objective To the authors’ knowledge, there are few valid data that describe the prevalence of comorbidity in type 2 diabetes mellitus (T2DM) patients seen in family practice. This study aimed to investigate the prevalence of comorbidities and their association with elevated (≥?7.0%) haemoglobin A1c (HbA1c) using a large sample of T2DM patients from primary care practices. Design A cross-sectional study in which multivariate logistic regression was applied to explore the association of comorbidities with elevated HbA1c. Setting Primary care practices in Croatia. Subjects Altogether, 10 264 patients with diabetes in 449 practices. Main outcome measures Comorbidities and elevated HbA1c. Results In total 7979 (77.7%) participants had comorbidity. The mean number of comorbidities was 1.6 (SD 1.28). Diseases of the circulatory system were the most common (7157, 69.7%), followed by endocrine and metabolic diseases (3093, 30.1%), and diseases of the musculoskeletal system and connective tissue (1437, 14.0%). After adjustment for age and sex, the number of comorbidities was significantly associated with HbA1c. The higher the number of comorbidities, the lower the HbA1c. The prevalence of physicians’ inertia was statistically significantly and negatively associated with the number of comorbidities (Mann–Whitney U test, Z?=?–12.34; p?Conclusion There is a high prevalence of comorbidity among T2DM patients in primary care. A negative association of number of comorbidities and HbA1c is probably moderated by physicians’ inertia in treatment of T2DM strictly according to guidelines.

• Key points

• There is a high prevalence of comorbidity among T2DM patients in primary care.

• Patients with breast cancer, obese patients, and those with dyslipidaemia and ischaemic heart disease were more likely to have increased HbA1c.

• The higher the number of comorbidities, the lower the HbA1c.

     

糖化血红蛋白对糖尿病的诊断价值分析

目的探讨糖化血红蛋白（HbA1c）在糖尿病（DM）诊断中的应用价值。方法 286例健康人和680例DM患者均行口服葡萄糖耐量试验（OGTT）,用特定蛋白分析仪检测HbA1c水平,用BS-420生化分析仪测定血糖,对结果进行分析。结果从健康组到DM组之间的HbA1c的变化关系可看出：DM组患者空腹血糖（FPG）、餐后2h血糖（2hPG）及HbA1c均明显高于健康组（均P〈0.01）,以HbA1c≥6.5%作为DM诊断临界值,其诊断灵敏度为99.18%,诊断特异性为94.45%,均优于以FPG≥7.0mmol/L作为诊断临界值的诊断灵敏度（76.43%）和诊断特异性（89.82%）。结论 HbA1c的值为6.5%时用于诊断DM,与FPG≥7.0mmol/L时联合应用可增加诊断DM的能力。     

Glycated hemoglobin A1c level is associated with high urinary albumin/creatinine ratio in non-diabetic adult population

Background: Regarding the association between glycated hemoglobin A1c (HbA1c) levels and microvascular complications, high HbA1c level in participants without diabetes mellitus (DM) may be associated with a high urinary albumin-to-creatinine ratio (UACR).

Patients and methods: Twelve thousand seven hundred and seventy four participants without DM were included in this study. The participants were divided into three groups according to HbA1c levels: a Low group (<5.7%), Middle group (5.7–6.0%), and High group (>6.0%). A high UACR was defined as UACR ≥3.9?mg/g for men and UACR ≥7.5?mg/g for women.

Results: The proportions of participants with a high UACR in the Low, Middle, and High groups were 22.4%, 27.9%, and 38.1%, respectively. Both univariate and multivariate analyses showed that logUACR was greatest in the High group compared to the other groups. For participants without metabolic syndrome (MetS), the proportions of participants with high UACR and logUACR values were greatest in the High group compared to the other groups. For participants with MetS, no differences were found for proportions of participants with high UACR and logUACR values in the Low, Middle, and High groups.

Conclusion: Non-DM participants with relatively high HbA1c levels should be closely monitored for UACR, especially if participants do not have MetS.

• KEY MESSAGES

• HbA1c level was positively associated with the proportion of participants with a high UACR and logUACR in participants without DM.

• For participants without MetS, the proportion of participants with a high UACR was greater in the High group than in the other groups and logUACR was greatest in the High group compared to the other groups.

• For participants with MetS, there were significant associations between HbA1c and the proportion of participants with a high UACR as a categorical variable or logUACR as a continuous variable, but the statistical significance of this finding was weak. No differences were found for proportions of participants with high UACR and logUACR values in the Low, Middle, and High groups.

     

Canagliflozin provides greater attainment of both HbA1c and body weight reduction versus sitagliptin in patients with type 2 diabetes

Objectives: To evaluate the proportion of patients with type 2 diabetes mellitus (T2DM) achieving reductions in both glycated hemoglobin (HbA1c) and body weight with canagliflozin, a sodium glucose co-transporter 2 inhibitor, versus sitagliptin over 52 weeks.

Methods: Data were pooled from two, randomized, Phase 3 studies of canagliflozin 100 and 300 mg versus sitagliptin 100 mg as add-on to metformin, and canagliflozin 300 mg versus sitagliptin 100 mg as add-on to metformin plus sulfonylurea (N = 1856). The composite end points of change from baseline in both HbA1c <0% and body weight <0 kg, and attainment of HbA1c <7.0% and body weight reduction ≥5% at Week 52 were evaluated. Safety was assessed based on adverse event reports.

Results: Canagliflozin provided reductions in HbA1c and body weight over 52 weeks versus sitagliptin. A greater proportion of patients had both HbA1c and body weight reductions with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (67.7%, 72.6%, and 44.1%, respectively). Among patients with HbA1c and body weight reductions, more patients achieved the composite end point of HbA1c <7.0% and body weight reduction ≥5% with canagliflozin 100 and 300 mg versus sitagliptin 100 mg (18.9%, 18.3%, and 5.7%, respectively). Canagliflozin was generally well tolerated.

Conclusions: A greater proportion of patients with T2DM achieved reductions in both HbA1c and body weight, and more patients with HbA1c and body weight reductions achieved HbA1c <7.0% and body weight reduction ≥5% with canagliflozin versus sitagliptin over 52 weeks.

Clinical trial registration: www.ClinicalTrials.gov identifiers are NCT01106677; NCT01137812.     

Are point-of-care measurements of glycated haemoglobin accurate in the critically ill?

IntroductionCritically ill patients with type 2 diabetes mellitus (T2DM) and chronic hyperglycaemia may benefit from a more liberal approach to glucose control than patients with previously normal glucose tolerance. It may therefore be useful to rapidly determine HbA1c concentrations. Point-of-care (POC) analysers offer rapid results but may be less accurate than laboratory analysis.Aim(s)The aim of this study was to determine agreement between POC and laboratory HbA1c testing in critically ill patients with T2DM.MethodsCritically ill patients with T2DM had concurrent laboratory, capillary-, and arterial-POC HbA1c measurements performed. Data are presented as mean (standard deviation) or median [interquartile range]. Measurement agreement was assessed by Lin's concordance correlation coefficient, Bland–Altman 95% limits of agreement, and classification by Cohen's kappa statistic.ResultsHbA1c analysis was performed for 26 patients. The time to obtain a result from POC analysis took a median of 9 [[7], [10]] minutes. Laboratory analysis took a median of 328 [257, 522] minutes from the time of test request to the time of report. Lin's correlation coefficient showed almost perfect agreement (0.99%) for arterial- vs capillary-POC and both POC methods vs arterial laboratory analysis. Bland–Altman plots showed a mean difference of 2.0 (3.7) with 95% limits of agreement of ?5.4 to 9.3 for capillary vs laboratory, 1.6 (3.4) and ?5.1 to 8.4 for arterial vs laboratory, and ?0.137 (2.6) and ?5.2 to 4.9 for capillary vs arterial. Patient classification as having inadequately controlled diabetes (>53 mmol/mol) showed 100% agreement across all tests.ConclusionsHbA1c values can be accurately and rapidly obtained using POC testing in the critically ill.     

基于超声弹性成像观察2型糖尿病患者股四头肌肌腱改变

目的 基于超声弹性成像观察2型糖尿病(T2DM)患者股四头肌肌腱改变。方法 回顾性分析80例T2DM患者(T2DM组)和80名健康人(对照组);比较2组一般资料及超声弹性成像参数,包括股四头肌肌腱近段、远段及中段与同侧股前脂肪垫比值[即应变率(SR)]的差异,并分析其与病程及糖化血红蛋白(HbA1c)的相关性。结果 T2DM组空腹血糖及HbA1c明显高于对照组(P均<0.05)。相比对照组,T2DM组股四头肌肌腱近段、中段及远段SR均明显增高(P均<0.05),以远段和近段增高更为显著(t=6.01、5.92)。T2DM组股四头肌肌腱近段、中段及远段SR与病程(r=0.45、0.20、0.43)和HbA1c(r=0.44、0.40、0.33)均呈正相关(P均<0.05)。结论 T2DM患者股四头肌肌腱SR明显增高,且与病程及HbA1c水平呈正相关。     

Hemoglobin A1c and glucose criteria identify different subjects as having type 2 diabetes in middle-aged and older populations: The KORA S4/F4 Study

Abstract

Objective. The American Diabetes Association (ADA) has recently recommended HbA1c for diagnosing diabetes as an alternative to glucose-based criteria. We compared the new HbA1c-based criteria for diagnosis of diabetes and prediabetes with the glucose-based criteria.

Research design and methods. In the population-based German KORA surveys (S4/F4) 1,764 non-diabetic participants aged 31–60 years and 896 participants aged 61–75 years underwent measurements of HbA1c, fasting plasma glucose (FPG), and 2-h glucose.

Results. Only 20% of all subjects diagnosed with diabetes by glucose or HbA1c criteria had diabetes by both criteria; for prediabetes, the corresponding figure was 23%. Using HbA1c ≥ 6.5%, the prevalence of diabetes was strongly reduced compared to the glucose criteria (0.7% instead of 2.3% in the middle-aged, 2.9% instead of 7.9% in the older subjects). Only 32.0% (middle-aged) and 43.2% (older group) of isolated impaired glucose tolerance (i-IGT) cases were detected by the HbA1c criterion (5.7% ≤ HbA1c < 6.5%).

Conclusion. By glucose and the new HbA1c diabetes criteria, different subjects are diagnosed with type 2 diabetes in middle-aged as well as older subjects. The new HbA1c criterion lacks sensitivity for impaired glucose tolerance.     

Efficacy and safety of empagliflozin in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Objectives: The prevalence of diabetes has increased in the recent decades and optimum glycemic control is required to reduce morbidity and mortality. We meta-analyzed randomized controlled trials in order to assess the efficacy and safety of empagliflozin compared to placebo in type 2 diabetes mellitus patients.

Methods: We included double-blind, placebo controlled trials of empagliflozin that evaluated glycemic efficacy and safety (10 mg or 25 mg) either as monotherapy or as add-on to existing diabetes pharmacotherapy.

Results: The results demonstrated significant improvements in HbA1c (SMD ?0.929%, 95 % CI ?1.064 to ?0.793, for 10 mg and ?1.064%, 95 % CI ?1.184 to ?0.944, for 25 mg) and FPG (SMD ?0.929%, 95 % CI ?1.064 to ?0.793, for 10 mg and ?1.064%, 95 % CI ?1.184 to ?0.944, for 25 mg) with empagliflozin monotherapy (n = 609) compared to placebo. Significant improvements in HbA1c [SMD ?1.582%, 95% CI ?2.164 to ?1.000, for 10 mg (n = 1079) and ?1.668%, 95% CI ?2.260 to ?1.077, for 25 mg (n = 1070)] and FPG [SMD ?0.865 mmol/L, 95 % CI ?1.309 to ?0.420, for 10 mg (n = 854) and ?0.996 mmol/L, 95% CI ?1.456 to ?0.536, for 25 mg (n = 854)] were also observed in empagliflozin add-on therapy trials. Reductions in blood pressure and body weight were also seen in both monotherapy and add-on therapy. Empagliflozin was associated with increased risk of hypoglycemia, genital and urinary tract infections (OR 1.043, 2.814, 1.119 respectively).

Conclusion: This meta-analysis shows empagliflozin is safe and effective for the treatment of T2DM along with existing diabetes pharmacotherapy.     

Impact of lorcaserin on glycemic control in overweight and obese patients with type 2 diabetes: analysis of week 52 responders and nonresponders

Objectives: Treatment guidelines for type 2 diabetes mellitus (T2DM) suggest weight loss as a means to maintain glycemic control. Lorcaserin has been approved for chronic weight management in the United States as an adjunct to a reduced-calorie diet and exercise, and the previous phase 3 Behavioral Modification and Lorcaserin for Obesity and Overweight Management in Diabetes Mellitus (BLOOM-DM) study has shown that, in addition to weight loss, lorcaserin is associated with improvements in glycemic parameters. In this post hoc analysis of the BLOOM-DM trial, the relationship between responder status (patients achieving ≥5% weight loss at Week 52) and glycemic and cardiometabolic parameters is evaluated.

Methods: Data are presented for patients receiving lorcaserin 10 mg twice daily or placebo for 52 weeks.

Results: More than twice as many patients receiving lorcaserin plus diet and exercise counseling were classified as Week 52 responders compared to those receiving diet and exercise counseling alone (37.5% vs. 16.1%, respectively; p < 0.001), and lorcaserin Week 52 responders had greater improvements vs. placebo Week 52 responders in FPG (?38.1 mg/dL vs. ?26.0 mg/dL) and HbA1c (?1.3% vs. ?1.0%). Furthermore, more lorcaserin-treated Week 52 responders decreased the number of concomitant oral antidiabetic medications (OADs) used, and fewer increased the number of OADs used, compared to placebo. Unexpectedly, lorcaserin Week 52 nonresponders also had substantial reductions in glycemic levels, despite very modest weight loss.

Conclusions: These data support lorcaserin use in overweight and obese patients with T2DM to promote weight loss and facilitate glycemic control.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT00603291     

Correlation of periodontal inflamed surface area with glycemic status in controlled and uncontrolled type 2 diabetes mellitus

BACKGROUNDThe bidirectional link between periodontitis and diabetes mellitus (DM) has been established. Periodontitis causes systemic inflammatory burden through inflammatory mediators. The currently utilized tools [clinical attachment loss (CAL) and probing pocket depth (PPD)] are linear measurements, that do not exactly quantify the inflammatory burden of periodontitis. Periodontal inflamed surface area (PISA) quantifies the surface area of bleeding pocket epithelium and estimates the inflammatory burden. Studies relating to the periodontal status of diabetic patients with and without microvascular complications are scarce. This study assessed the proportion of periodontitis and correlation of PISA with glycemic status in controlled, uncontrolled type 2 DM (T2DM) with and without microvascular complications.AIMTo assess the proportion of periodontitis and correlation of PISA with glycemic status in controlled, and uncontrolled T2DM with and without microvascular complications.METHODSThis study comprised 180 T2DM patients. Based on glycated hemoglobin (HbA1c) levels, they were grouped into: (1) Controlled T2DMgroup: (HbA1c ≤ 7%); (2) Uncontrolled T2DM group: (HbA1c > 7%) without microvascular complications; and (3) Uncontrolled T2DM group: (HbA1c > 7%) with microvascular complications. Each group comprised 60 patients. All patients were assessed for periodontal parameters (Bleeding on Probing, PPD, CAL, Oral hygiene index simplified and PISA), and systemic parameters (HbA1c, fasting plasma glucose and post prandial plasma glucose).RESULTSThe proportion of periodontitis among controlled T2DM group, uncontrolled T2DM group without microvascular complications, uncontrolled T2DM group with microvascular complications was 75%, 93.4% and 96.6% respectively. Extent and severity of periodontitis were high in the uncontrolled T2DM group. A significant positive correlation was found between PISA and HbA1c among all patients (r = 0.393, P < 0.001). The dose–response relationship between PISA and HbA1c was observed. An increase of PISA with 168 mm² was associated with a 1.0% increase of HbA1c. CONCLUSIONHigh proportion and severity of periodontitis, and increased inflamed surface area in uncontrolled T2DM may have contributed to the poor glycemic control and microvascular complications.     

Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma?

Background: Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.

Methods: Whole blood samples were collected in K₂EDTA tubes from individuals homozygous for HbA (n?=?40) and heterozygous for Hb-Tacoma (n?=?20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at ?80?°C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method.

Results: When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. Conclusions: The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.     

Glycated albumin as a glycaemic marker in patients with advanced chronic kidney disease and anaemia: a preliminary report

Abstract

Background: The association between glycated albumin (GA) and glycaemic status has not been fully described in patients with advanced chronic kidney disease (CKD) in relation to anaemia. The aim of this study was to evaluate the relationship between GA and fasting plasma glucose (FPG) and HbA1c in patients with advanced CKD and to evaluate the influence of anaemia in such relationship.

Materials and methods: Patients with CKD stage 4 or 5 were included in the study. eGFR was calculated by the CKD-EPI creatinine equation. Plasma GA was measured by an enzymatic method.

Results: Eighty-one patients were included in the study, 46 (57%) were males; the mean age was 67?±?14?years. HbA1c was correlated with Hb (r?=?0.39; p?=?.0003), and no significant correlation was detected between plasma GA and serum albumin (p?=?.82). A significant association between FPG and GA (r²?=?0.41; p?r²?=?0.42; p?r²?=?0.55; p?Conclusions: GA, alone or in combination with other biomarkers, can be considered for the evaluation of glycaemic status in patients with advanced CKD and severe anaemia.     

Lithium poisoning in the intensive care unit: predictive factors of severity and indications for extracorporeal toxin removal to improve outcome

Context: Lithium is responsible for life-threatening poisoning, not consistently improved by extracorporeal toxin removal (ECTR).

Objective: Our aim was to identify predictive factors on admission of poisoning severity and based on an evaluation of practice, report indications for ECTR susceptible to improve outcome

Methods: We performed a retrospective cohort study including all lithium-poisoned patients admitted to the ICU in a university hospital. The usual clinical, biological and toxicological variables were collected. Poisoning severity was defined by seizures, catecholamine infusion, mechanical ventilation >48?h and/or fatality. Univariate followed by multiple logistic regression analyses were performed to identify prognosticators of poisoning severity and ECTR use.

Results: From 1992 to 2013, 128 lithium-poisoned patients including acutely (10%), acute-on-chronically (63%) and chronically poisoned patients (27%) were included. The presumed ingested dose of lithium was 17.0?g [8.0–24.5] (median [25th–75th percentiles]). Serum lithium concentrations were 2.6?mmol/l [1.5–4.6], 2.8?mmol/l [1.8–4.5] and 2.8?mmol/l [2.1–3.0] on admission, peaking at 3.6?mmol/l [2.6; 6.2], 4.3?mmol/l [2.4; 6.2] and 2.8?mmol/l [2.1; 3.1] in the three groups, respectively. Severe poisoning occurred in 48 patients (38%) including four fatalities. Using the regression analysis, predictive factors of poisoning severity were Glasgow coma score ≤10 (Odds ratio (OR), 11.1; 95% confidence interval (CI), [4.1–33.3], p?p?=?0.005). Ninety-eight patients (77%) developed acute kidney injury according to KDIGO criteria and 22 (17%) were treated with ECTR. Peak lithium concentration ≥5.2?mmol/l (OR, 22.4; CI, [6.4–96.4]; p?p?=?0.01) were associated with ECTR use. Only 21/46 patients who presented one of these two criteria were actually treated with ECTR. More significant neurological impairment persisted on discharge in patients not treated with ECTR (p?=?0.0007) despite not significantly shorter length of ICU stay.

Conclusions: Lithium poisoning is responsible for severe impairments but rare fatalities. Severity can be predicted on admission using Glasgow coma score and lithium concentration. Our results suggest that ECTR could be indicated if serum lithium ≥5.2?mmol/l or creatinine ≥200?μmol/l.     

双能量CT测量胰腺细胞外体积分数及标准化碘浓度评估2型糖尿病

目的 观察双能量CT测量胰腺细胞外体积分数(fECV)及标准化碘浓度(nIC)评估2型糖尿病(T2DM)的价值。方法 根据T2DM诊断标准将76例接受腹部双能量CT三期增强扫描患者分为糖尿病组(n=34)和非糖尿病组(n=42),于平衡期碘基图测量胰腺fECV和nIC;对比组间差异，分析胰腺fECV、nIC与糖化血红蛋白(HbA1c)的相关性，评估其诊断T2DM的价值。结果 糖尿病组HbA1c、胰腺fECV及nIC均明显高于非糖尿病组(P均<0.001)。胰腺fECV(r_s=0.593、0.397)及nIC(r_s=0.479、0.424)在全部76例患者及糖尿病组34例患者中均与HbA1c呈中等或弱正相关(P均<0.05)。胰腺fECV与nIC联合诊断T2DM的敏感度、特异度及曲线下面积(AUC)分别为76.50%、83.30%及0.824[95%CI(0.728,0.919)],其AUC明显高于单一nIC(Z=2.002,P=0.045)而与单一fECV无明显差异(Z=1.158,P=0.247)。结论 双能量CT所测胰腺fEC...     

A novel approach to control hyperglycemia in type 2 diabetes: Sodium glucose co-transport (SGLT) inhibitors. Systematic review and meta-analysis of randomized trials

Abstract

Background. Current treatment of hyperglycemia in type 2 diabetes (T2DM) is often ineffective and has unwanted effects. Therefore, novel antidiabetic drugs are under development.

Objective. To assess efficacy and safety of the new antidiabetic drugs sodium glucose co-transport-2 (SGLT2) inhibitors in T2DM.

Design and setting. Among 151 articles published on MEDLINE, Cochrane Library, EMBASE, PubMed, International meeting abstracts through December 2010, 13 randomized placebo-controlled trials (RCT) were included.

Measurements. Two reviewers retrieved articles and evaluated study quality by appropriate scores. Main outcomes were pooled using random- or fixed-effects models.

Results. Dapagliflozin significantly reduced HbA1c (weighted mean difference (WMD) ?0.52%; 95% CI ?0.46, ?0.57%; P < 0.00001) fasting plasma glucose (WMD ?18.28 mg/dL; 95% CI ?20.66, ?15.89; P < 0.00001), body mass index (WMD ?1.17%; ?1.41, ?0.92%; P < 0.00001), systolic (WMD ?4.08 mmHg; ?4.91, ?3.24), and diastolic (WMD ?1.16 mmHg; ?1.67, ?0.66) blood pressure, and serum uric acid (WMD ?41.50 μmol/L; ?47.22, ?35.79). Other SGLT2 inhibitors showed similar results. Dapagliflozin treatment increased the risk of urinary (OR 1.34; 1.05–1.71) and genital (OR 3.57; 2.59–4.93) tract infection; it also mildly increased the risk of hypoglycemia (OR 1.27; 1.05–1.53) when co-administered with insulin.

Limitations. Limitations of the literature include the small number, size, and duration of RCTs.

Conclusions. Pending confirmation from larger RCTs, this analysis shows SGLT2 inhibitors are safe and effective for hyperglycemia treatment in T2DM.