Glycated Hemoglobin Level and Mortality in a Nondiabetic Population with CKD

Background and objectives

Glycated hemoglobin (HbA_1c) is used to diagnose diabetes mellitus (DM) and guide its management. The association between higher HbA_1c and progression to ESRD and mortality has been demonstrated in populations with DM. This study examined the association between HbA_1c and these end points in a population with CKD and without DM.

Design, setting, participants, & measurements

In the hospital-based NephroTest cohort study, measured GFR (mGFR) was taken by ⁵¹Cr-EDTA renal clearance and HbA_1c in 1165 adults with nondialysis CKD stages 1–5 and without DM between January 2000 and December 2010. The median follow-up was 3.48 years (interquartile range, 1.94–5.82) for the competing events of ESRD and pre-ESRD mortality. Time-fixed and time-dependent Cox models were used to estimate hazard ratios (HRs) for ESRD and mortality according to HbA_1c, treated continuously or in tertiles.

Results

At inclusion, the mean mGFR was 42.2±19.9 ml/min per 1.73 m², and the mean HbA_1c value was 5.5%±0.5%. During follow-up, 109 patients died, and 162 patients reached ESRD. Pre-ESRD mortality was significantly associated with HbA_1c treated continuously: for every 1% higher HbA_1c, the crude HR was 2.16 (95% confidence interval [95% CI], 1.27 to 3.68), and it was 1.85 (95% CI, 1.05 to 3.24) after adjustment for mGFR and other risk factors of death. After excluding incident diabetes over time, the updated mean of HbA_1c remained significantly associated with higher mortality risk: adjusted HR for the highest (5.7%–6.4%) versus the lowest tertile (<5.3%) was 2.62 (95% CI, 1.16 to 5.91). There was no association with ESRD risk after adjustment for risk factors of CKD progression.

Conclusions

In a CKD cohort, HbA_1c values in the prediabetes range are associated with mortality. Such values should be therefore included among the risk factors for negative outcomes in CKD populations.     

Gender and ethnic differences in the control of hyperlipidaemia and other vascular risk factors: insights from the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) study

Aim

The aim of the CEntralised Pan-South African survey on tHE Under-treatment of hypercholeSterolaemia (CEPHEUS SA) was to evaluate the current use and efficacy of lipid-lowering drugs (LLDs) in urban patients of different ethnicity with hyperlipidaemia, and to identify possible patient characteristics associated with failure to achieve low-density lipoprotein cholesterol (LDL-C) targets. There is little published data on LDL-C attainment from developing countries.

Methods

The survey was conducted in 69 study centres in South Africa and recruited consecutive patients who had been prescribed LLDs for at least three months with no dose adjustment for six weeks. All patients provided written consent. One visit was scheduled for data collection, including fasting lipid and glucose, and HbA_1c levels.

Results

Of the 3 001 patients recruited, 2 996 were included in the final analyses; 1 385 subjects were of Caucasian origin (818 male), 510 of African ancestry (168 male), 481 of mixed ancestry (222 male) and 620 of Asian origin (364 male). Only 60.5% of patients on LLDs for at least three months achieved the LDL-C targets recommended by the NCEP ATP III/2004 updated NCEP ATP III guidelines and 52.3% the fourth JETF/South African guidelines. African females were on average younger than females of other ethnic origins, and had the lowest smoking rates but the highest prevalence of obesity, hypertension, the metabolic syndrome and diabetes mellitus (DM), with the worst glycaemic control. Although women were less likely than men to reach goal [OR 0.65 (CI 0.54–0.77), p < 0.001 for NCEP ATP III guidelines and OR 0.76 (CI 0.64–0.91), p < 0.003 for fourth JETF guidelines], women of African ancestry were just as likely not to reach goal as their Caucasian counterparts.

Conclusion

The results of this survey highlight the sub-optimal lipid control achieved in many South African patients, and profile important gender and ethnic differences. Control of cardiovascular disease risk factors across gender and ethnic groups remains poor.     

Relation between HbA1c and incident cardiovascular disease over a period of 6 years in the Hong Kong population

Aim

The current trend on diabetes management advocates replacing the paradigm from a uniform to an individualized patient-centered haemoglobin A_1c (HbA_1c) target, but there is no consensus on the optimal HbA_1c level. The study aimed at examining the association between HbA_1c and the risk of cardiovascular diseases (CVD) for diabetic patients with different characteristics, in order to identify patient-centered treatment targets.

Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate treatment in diabetes patients with rheumatic diseases

Objective

Prior research demonstrates that hydroxychloroquine (HCQ) lowers glycosylated hemoglobin (HbA_1c) in diabetes patients without rheumatic disease. We examined medical records of patients with diabetes mellitus (DM) and concomitant rheumatic illness to measure changes in HbA_1c after starting HCQ or methotrexate (MTX).

Methods

We used electronic medical records to identify patients beginning treatment with either HCQ or MTX who had a diagnosis of DM (or a pretreatment HbA_1c value of ≥7%) and at least 1 HbA_1c measurement both before and within 12 months after initiation of treatment. Using a structured medical record abstraction, we examined rheumatic disease diagnosis, cumulative steroid use, duration (months) between drug initiation and lowest HbA_1c value, a change in DM medication, body mass index (BMI), age, and sex. Adjusted linear regression models determined changes in HbA_1c from pretreatment values to the lowest posttreatment values within 12 months.

Results

We identified 45 patients taking HCQ and 37 patients taking MTX who met the inclusion criteria. Rheumatoid arthritis had been diagnosed in approximately half of the patients in each group. Age, sex, and mean pretreatment HbA_1c levels were similar across groups. The mean BMI of those taking HCQ (35.4 kg/m²) was slightly higher than that of those taking MTX (32.2 kg/m²) (P = 0.13). Glucocorticoid use appeared more common in those taking MTX (46%) than in those taking HCQ (29%) (P = 0.17). The mean reduction in HbA_1c from pretreatment values to the lowest posttreatment values was 0.66% (95% confidence interval [95% CI] 0.26, 1.05) in those taking HCQ compared with 0.11% (95% CI −0.18, 0.40) in those taking MTX. In fully adjusted analyses, the reduction in HbA_1c among those taking HCQ was 0.54% greater than the reduction among those taking MTX (P = 0.041).

Conclusion

HCQ initiation was associated with a significantly greater reduction in HbA_1c as compared with MTX initiation among diabetes patients with rheumatic disease.

     

The Effect of a Hypertension Self-Management Intervention on Diabetes and Cholesterol Control

Background

Most patient chronic disease self-management interventions target single-disease outcomes. We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin (HbA_1c) and low-density lipoprotein cholesterol (LDL-C).

Methods

We evaluated patients from the Veterans Study to Improve the Control of Hypertension, a 2-year randomized controlled trial. Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care. Although the study focused on hypertension self-management, we compared changes in HbA_1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period. Changes in these laboratory values over time were compared between the 2 treatment groups using linear mixed-effects models.

Results

For the patients with diabetes, the hypertension self-management intervention resulted in a 0.46% reduction in HbA_1c over 2 years compared with usual care (95% confidence interval, 0.04%-0.89%; P = .03). For LDL-C, there was a minimal 0.9 mg/dL between-group difference that was not statistically significant (95% confidence interval, −7.3-5.6 mg/dL; P = .79).

Conclusions

There was a significant effect of the self-management intervention on the unintended target of HbA_1c,but not LDL-C. Chronic disease self-management interventions might have “spill-over” effects on patients' comorbid chronic conditions.     

Oscillometric blood pressure reference values of African full-term neonates in their first days postpartum

Background

Knowing the normative blood pressure (BP) in a newborn baby is important in order to identify abnormal BP readings. This study was done to determine normative BP values of Nigerian newborns, using the 8100 Dinamap monitor.

Methods

Consecutive full-term neonates delivered in a tertiary centre in Nigeria were recruited for the study. The babies’ systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures were measured within the first four days after birth.

Results

A total of 473 babies were recruited for the study. The mean SBP, DBP and MAP readings on day 1 were 66.8 ± 7.7, 38.5 ± 6.3 and 47.9 ± 6.3 mmHg, respectively. The day 1 SBP of babies > 4 kg were significantly higher than those who weighed < 2.5 and 2.5–4 kg (p = 0.01, p = 0.05), respectively.

Conclusion

This study provided current normative SBP, DBP and MAP values for Nigerian neonates. The BP readings compared with their Caucasian counterparts.     

Effect of Continuous Positive Airway Pressure on Hemoglobin A1c in Patients with Obstructive Sleep Apnea: A Systematic Review and Meta-analysis

Background

There is little conclusive data regarding the effect of continuous positive airway pressure (CPAP) on glycated hemoglobin (HbA_1c). An earlier meta-analysis included two randomized controlled trials (RCTs) and found no significant effect of CPAP on HbA_1c. The meta-analysis presented here was conducted to include all relevant observational studies and RCTs on the effect of CPAP on HbA_1c.

Methods

We searched the PubMed database for all studies published prior to March 2012 for trials of the effect of CPAP on HbA_1c. Data from observational studies and RCTs that met the inclusion criteria were extracted for pre- and post-treatment HbA_1c.

Results

A total of nine studies that included 151 subjects met the inclusion criteria. The duration of the studies ranged from 41?days to 6?months. The mean net change in the HbA_1c was ?0.06?% [95?% CI: ?0.24, 0.12] (p?=?0.5). Five of the nine studies, with a total of 112 subjects, comprised patients with diabetes mellitus (DM) type 2. The mean net change in HbA_1c for the subjects with DM type 2 was 0.08?% [95?% CI: ?0.26, 0.42] (p?=?0.65). The mean net change in HbA_1c for subjects with DM type 2 in studies that were at least 3?months in duration was 0.16?% [95?% CI: ?0.26, 0.58] (p?=?0.45).

Conclusions

This meta-analysis found that CPAP does not reduce HbA_1c levels when used in the short term.     

Self‐perception of glycemic control among Japanese type 2 diabetic patients: accuracy of patient perception and characteristics of patients with misperception

Aims

Some diabetic patients, despite reporting a good perception of their glycemic control, actually show poor control and this misperception might well hinder successful diabetes management. This study aimed to assess patients'' self‐perception of glycemic control and to clarify factors associated with misperception of glycemic control status.

Methods

Baseline data from a hospital‐based prospective cohort of 519 type 2 diabetic patients were analyzed. Self‐perception of glycemic control and other items, including sociodemographic factors and blood test data, were determined from a self‐administered questionnaire and medical records. Factors associated with misperception were examined by age group (elderly [aged ≥ 65 years] vs non‐elderly [aged < 65 years]) using multiple logistic regression analysis.

Results

Among poorly controlled patients, misperception was higher in the elderly (glycated hemoglobin [HbA_1c] 7.4–8.3, 55.1%; HbA_1c >8.4, 44.8%) than in the non‐elderly (HbA_1c 7.4–8.3, 20.0%; HbA_1c >8.4, 18.9%). The factors significantly associated with misperception were as follows: high lifestyle regimen adherence in both age groups (non‐elderly group odds ratio [OR] 5.23; elderly group OR 5.15, respectively); high family support (OR = 7.32), failure to achieve blood pressure control (OR = 6.94) and having diabetic complications (OR = 0.06) among the non‐elderly; and long duration of diabetes (OR = 4.06) among the elderly.

Conclusions

For better management of diabetes, physicians should pay attention to the patient characteristics associated with misperception among uncontrolled diabetic patients, particularly among those who are elderly.     

Cardioversion: What to choose? Etomidate or propofol

Context:

Electrical cardioversion is a short painful procedure to regain normal sinus rhythm requiring anaesthesia for haemodynamic stability, sedation, analgesia and early recovery.

Aims:

To compare propofol and etomidate as sedatives during cardioversion.

Settings and Design:

Single centred, prospective and randomized single blind study comprising 60 patients.

Subjects and Methods:

Patients more than 18 years, American Society of Anesthesiologists I/II/III grades undergoing elective cardioversion, randomly divided to receive propofol 1 mg/kg intravenous (IV) bolus followed by 0.5 mg/kg (Group P, n = 30) or etomidate (Group E, n = 30) 0.1 mg/kg followed by 0.05 mg/kg. All patients received IV fentanyl (1 μg/kg) before procedure. Heart rate, blood pressure (BP) (systolic BP [SBP], diastolic BP [DBP], mean arterial pressure), respiratory rate, Aldrete recovery score (ARS) and Ramsay sedation score (RSS) were assessed at 1, 2, 5, 10, 15, 20 and 30 min post cardioversion. Incidence of hypotension, respiratory depression and side effects were compared.

Statistical analysis used:

Student''s unpaired t-test, Chi-square test and Mann–Whitney test. P < 0.05 was taken as significant.

Results:

Group P showed significant fall in SBP, DBP, and mean BP at 2 min after cardioversion. Hypotension (33.3% Group P vs. 16.65% Group E) occurred more with propofol (P < 0.05). Group E showed better ARS at 1, 2, 5, 10, 15 and 20 min. Time required to attain RSS = 2 (659.1 s Group P and 435.7 s Group E) indicated longer recovery with propofol. Left atrial size (35.5-42.5 mm) did not affect success rate of cardioversion (80% Group P vs. 83.3% Group E). Incidence of myoclonus (Group E 26.67% vs. Group P 0%) showed significant difference.

Conclusions:

Etomidate/fentanyl is superior over propofol/fentanyl during cardioversion for quick recovery and haemodynamic stability.     

Is β-cell failure in type 2 diabetes mellitus reversible?

BACKGROUND:

In the UK Prospective Diabetes Study (UKPDS), many subjects maintained glycemic goal (HbA_1c < 7.0%) at 9 years, showing that β-cell function was preserved and that the initial decline in β-cell function recovered with sulphonylureas. Moreover, obese subjects using high daily doses of insulin for several years rarely require insulin or oral hypoglycemic agents to maintain their glycemic goal following weight loss achieved by gastric bypass surgery. Thus, declining β-cell function during the course of type 2 diabetes mellitus (T2DM) is neither universal nor permanent.

OBJECTIVE:

To assess β-cell function in morbidly obese subjects before insulin withdrawal and on attaining the glycemic goal with weight loss and oral agents.

MATERIALS AND METHODS:

Serum C-peptide (CPEP) and glucose (G) concentrations were determined up to 180 min during an oral glucose tolerance test (OGTT) with 75 glucose in 10 obese men with T2DM, before insulin withdrawal, and on achieving the glycemic goal with metformin, glimepiride, and weight loss. Ten age-matched healthy men participated as controls. Cumulative responses (CR) of CPEP and G were calculated by adding differences between the level at each time-period during OGTT and fasting (F) concentration. β-Cell function was expressed as the FCPEP as well as the insulinogenic index (CRCPEP/CRG). Insulin sensitivity was determined as FCEP × FG.

RESULTS:

FCPEP was decreased, though still present, prior to insulin withdrawal. Moreover, on attaining the glycemic goal over 6-9 months, FCPEP, CRPEP/CRG, and FCPEP × FG improved markedly (P < 0.001).

CONCLUSION:

Decline in β-cell function in morbidly obese T2DM may not be progressive and is reversible on improving insulin sensitivity and on eliminating the inhibition by exogenous insulin.     

A randomized comparison of a commercially available portion-controlled weight-loss intervention with a diabetes self-management education program

Objective:

This study examined the efficacy of a commercially available, portion-controlled diet (PCD) on body weight and HbA_1c over 6 months in obese patients with type 2 diabetes.

Research Design and Methods:

One-hundred participants with a mean±s.d. age of 55.6±10.6 year, body weight of 102.9±18.4 kg and HbA_1c of 7.7±1.3% were randomly assigned to a 9-session group lifestyle intervention that included a PCD or to a 9-session group program of diabetes self-management education (DSME). Participants in the two groups were prescribed the same goals for energy intake (1250–1550 kcal per day) and physical activity (200 min per week).

Results:

While both groups produced significant improvements in weight and HbA_1c after 6 months of treatment, PCD participants lost 7.3 kg [95% confidence interval (CI): −5.8 to −8.8 kg], compared with 2.2 kg (95% CI: −0.7 to −3.7 kg) in the DSME group (P<0.0001). Significantly more PCD than DSME participants lost ⩾5% of initial weight (54.0% vs 14.0%, P<0.0001) and ⩾10% (26.0% vs 6.0%, P<0.0001). HbA_1c declined by 0.7% (95% CI: −0.4 to −1.0%) in the PCD group, compared with 0.4% (95% CI: −0.1 to −0.7%) in DSME (P<0.026). Across both groups, larger weight losses were associated with greater reductions in HbA_1c (r=0.52, P<0.0001).

Conclusions:

These findings demonstrate that a commercially available portion-controlled meal plan can induce clinically meaningful improvements in weight and glycemic control in obese individuals with type 2 diabetes. These data have implications for the management of obesity in primary care, as now provided by the Centers for Medicare and Medicaid Services.     

Blood glucose and pressure controls in diabetic kidney disease: Narrative review of adherence,barriers and evidence of achievement

Aims

To review the epidemiology and the clinical evidence regarding achieving blood pressure (BP) and blood glucose control in patients with chronic kidney disease (CKD) and diabetes mellitus (DM), with emphasis on adherence and barriers within the context of Australian clinical guidelines. This article then considers Australian services aimed at BP, DM, and CKD, guideline adherence and control.

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus

Aims/Introduction

We investigated the efficacy and safety of repaglinide as an add‐on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise.

Materials and methods

In the 16‐week multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group trial (the phase III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36‐week, multicenter, uncontrolled, dose‐titration method study was extended to a total duration of 52 weeks (the long‐term study). The primary end‐point of each study was a change in glycated hemoglobin (HbA_1c) from baseline.

Results

After 16 weeks, mean reductions in HbA_1c were significantly greater for the repaglinide group than for the placebo group (–0.98 ± 0.72% vs 0.13 ± 0.63%, P < 0.001). In the long‐term study, the mean change in HbA_1c was −0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase III study, and 78.3% in the long‐term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long‐term study, respectively.

Conclusions

Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA_1c at week 16 and in a significant long‐term improvement in HbA_1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI‐101202 and JapicCTI‐101203).     

HbA<Subscript>1c</Subscript> is associated with altered expression in blood of cell cycle- and immune response-related genes

Aims/hypothesis

Individuals with type 2 diabetes are heterogeneous in their glycaemic control as tracked by blood HbA_1c levels. Here, we investigated the extent to which gene expression levels in blood reflect current and future HbA_1c levels.

Methods

HbA_1c levels at baseline and 1 and 2 year follow-up were compared with gene expression levels in 391 individuals with type 2 diabetes from the Hoorn Diabetes Care System Cohort (15,564 genes, RNA sequencing). The functions of associated baseline genes were investigated further using pathway enrichment analysis. Using publicly available data, we investigated whether the genes identified are also associated with HbA_1c in the target tissues, muscle and pancreas.

Results

At baseline, 220 genes (1.4%) were associated with baseline HbA_1c. Identified genes were enriched for cell cycle and complement system activation pathways. The association of 15 genes extended to the target tissues, muscle (n = 113) and pancreatic islets (n = 115). At follow-up, expression of 25 genes (0.16%) associated with 1 year HbA_1c and nine genes (0.06%) with 2 year HbA_1c. Five genes overlapped across all time points, and 18 additional genes between baseline and 1 year follow-up. After adjustment for baseline HbA_1c, the number of significant genes at 1 and 2 years markedly decreased, suggesting that gene expression levels in whole blood reflect the current glycaemic state and but not necessarily the future glycaemic state.

Conclusions/interpretation

HbA_1c levels in individuals with type 2 diabetes are associated with expression levels of genes that link to the cell cycle and complement system activation.

     

Degree of control and delayed intensification of antihyperglycaemic treatment in type 2 diabetes mellitus patients in primary care in Spain

Objectives

Primary aim: to determine the degree of control of HbA_1c at the time of treatment intensification (TI) in T2DM patients. Secondary aims: fasting plasma glucose levels; estimation of the elapsed time between HbA_1c exceeding 7% and TI; antidiabetic combinations used, % patients with good cardiometabolic control (LDL-c < 100 mg/dL; SBP < 130 and DPB < 80 mmHg and HbA_1c < 7%).

Research design and methods

One-cohort, multicenter, retrospective, observational study conducted in Spain. Patients diagnosed with T2DM that had switched from monotherapy to combination antidiabetic therapy were evaluated at baseline and after one year of follow-up.

Results

A total of 1202 T2DM patients were analyzed. At the time of TI: mean HbA_1c 8.1%; median time of uncontrolled disease: 2.0 years. After one-year of TI: significant reduction in mean HbA_1c (8.1% vs.7.0%, p < 0.001) and a mean fasting plasma glucose levels reduction (181.1 mg/dL vs.144.1 mg/dL, p < 0.001) was also observed. The percentage of patients under glycemic control (HbA_1c < 7%) increased from 12.2% to 51.6% (p < 0.001). Most common antidiabetic combinations: metformin + sulfonylurea (44.1%) and metformin + thiazolidindione (15.9%).

Conclusions

In the population of T2DM patients analyzed, TI was carried out when HbA_1c values were above those recommended in clinical guidelines (≤7%), with a delay of two years to address the second step of therapy, despite the consensus recommendation of the ADA/EASD of 3 months. TI was shown to be effective since addition of a second antidiabetic drug led to an average reduction of HbA_1c of approximately 1%. Metformin was the drug most commonly used as monotherapy being the most frequent combination metformin + sulfonylurea.     

Does intravenous sildenafil clinically ameliorate pulmonary hypertension during perioperative management of congenital heart diseases in children? – A prospective randomized study

Background:

Pulmonary hypertension (PHT), if present, can be a significant cause of increased morbidity and mortality in children undergoing surgery for congenital heart diseases (CHD). Various techniques and drugs have been used perioperatively to alleviate the effects of PHT. Intravenous (IV) sildenafil is one of them and not many studies validate its clinical use.

Aims and Objectives:

To compare perioperative PaO₂ – FiO₂ ratio peak filling rate (PFR), systolic pulmonary artery pressure (PAP) – systolic aortic pressure (AoP) ratio, extubation time, and Intensive Care Unit (ICU) stay between two groups of children when one of them is administered IV sildenafil perioperatively during surgery for CHDs.

Materials and Methods:

Patients with ventricular septal defects and proven PHT, <14 years of age, all American Society of Anesthesiologists physical status III, undergoing cardiac surgery, were enrolled into two groups – Group S (IV sildenafil) and Group C (control) – over a period of 14 months, starting from October 2013. Independent t-test and Mann–Whitney U-test were used to compare the various parameters between two groups.

Results:

PFR was higher throughout, perioperatively, in Group S. PAP/AoP was 0.3 and 0.4 in Group S and Group C, respectively. In Group S, mean group extubation time was 7 ± 7.34 h, whereas in Group C it was 22.1 ± 10.6. Postoperative ICU stay in Group S and Group C were 42.3 ± 8.8 h and 64.4 ± 15.9 h, respectively.

Conclusion:

IV sildenafil, when used perioperatively, in children with CHD having PHT undergoing corrective surgery, improves not only PaO₂ – FiO₂ ratio and PAP – AoP ratio but also reduces extubation time and postoperative ICU stay.     

Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized,open‐label,parallel‐group,multicenter trial

Aims/Introduction

The present study was to compare the efficacy and safety of subject‐driven and investigator‐driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID).

Materials and Methods

In this 20‐week, randomized, open‐label, two‐group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self‐mixed human insulin were randomized 1:1 to subject‐driven or investigator‐driven titration of BIAsp 30 BID, in combination with metformin and/or α‐glucosidase inhibitors. Dose adjustment was decided by patients in the subject‐driven group after training, and by investigators in the investigator‐driven group.

Results

Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA_1c) reduction was 14.5 mmol/mol (1.33%) in the subject‐driven group and 14.3 mmol/mol (1.31%) in the investigator‐driven group. Non‐inferiority of subject‐titration vs investigator‐titration in reducing HbA_1c was confirmed, with estimated treatment difference −0.26 mmol/mol (95% confidence interval −2.05, 1.53) (–0.02%, 95% confidence interval –0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self‐measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient‐year) was reported in the subject‐driven (1.10) and investigator‐driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA_1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA_1c target without confirmed hypoglycemia throughout the trial in the subject‐driven and investigator‐driven groups, respectively.

Conclusions

Subject‐titration of BIAsp 30 BID was as efficacious and well‐tolerated as investigator‐titration. The present study supported patients to self‐titrate BIAsp 30 BID under physicians’ supervision.     

Comparison of insulin detemir and insulin glargine using a basal‐bolus regimen in a randomized,controlled clinical study in patients with type 2 diabetes

Background

This treat‐to‐target study compared the efficacy and safety of insulin detemir (IDet) and insulin glargine (IGla) in a basal‐bolus (insulin aspart) regimen in type 2 diabetes.

Methods

385 patients were randomized 2 : 1 (IDet : IGla). Non‐inferiority of IDet to IGla was determined by HbA_1c 95% CI upper limit <0.4.

Results

IDet and IGla showed similar efficacy in HbA_1c reduction at 26 weeks, as the non‐inferiority criterion was met at 26 weeks (LS mean [Det–Gla]: 0.207; 95% CI: 0.0149,0.3995). It appeared that IGla in some cases did better than IDet in terms of HbA_1c, but the difference (0.207%) was not clinically meaningful. Based on the CONSORT guideline, non‐inferiority analysis using the LOCF approach was inconclusive regarding possible inferiority of delta 0.4 (LS mean of [Det–Gla]: 0.307; 95% CI: 0.1023, 0.5109). HbA_1c decreased significantly from baseline in IDet (?1.1% [26 weeks], ?0.9% [LOCF], p < 0.001) and in IGla (?1.3% [26 weeks, LOCF], p < 0.001). Final HbA_1c were 7.1% (26 weeks) and 7.3% (LOCF) in IDet, and 6.9% (26 weeks) and 7.0% (LOCF) in IGla. Final FPG were 130 mg/dL (26 weeks) and 135 mg/dL (LOCF) in IDet, and 134 mg/dL (26 weeks) and 137 mg/dL (LOCF) in IGla. There was significantly less weight gain in IDet‐treated patients (1.2 ± 3.96 kg versus 2.7 ± 3.94 kg, p = 0.001). Hypoglycemia risk was comparable between groups. The majority of IDet‐treated patients (87.4%) remained on a once‐daily basal insulin regimen throughout the study.

Conclusions

IDet and IGla were both effective and safe treatments for glycemic control in a basal‐bolus regimen for type 2 diabetes. Clinically significant reductions in HbA_1c were achieved in both groups, but with significantly less weight gain in the IDet group at comparable basal insulin dosage. Copyright © 2009 John Wiley & Sons, Ltd.

     

Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial

Aims/hypothesis

Previous studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

Methods

We studied participants in the ADVANCE trial with data available for baseline HbA_1c and fasting plasma glucose (FPG) (n?=?11,083). HGI is the difference between observed HbA_1c and HbA_1c predicted from a simple linear regression of HbA_1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA_1c.

Results

Intensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p?=?0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA_1c. Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14–17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA_1c was a stronger predictor of these outcomes than HGI.

Conclusions/interpretation

HGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA_1c. Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA_1c, clinical use of HGI in type 2 diabetes cannot currently be recommended.

     

Is the prevalence of pre-eclampsia affected by HIV/AIDS? A retrospective case–control study

Objective

To evaluate the rate of HIV/AIDS (and CD₄ levels) in women with pre-eclampsia compared to that of a control group.

Methods

This was a retrospective case–control study in a tertiary and regional hospital in South Africa. We reviewed the hospital records of women who had delivered in these hospitals between 1 January 2008 and 30 June 2010. The records of women with pre-eclampsia during the study period were analysed. Their HIV infection rate was compared to that of a control group consisting of normotensive healthy pregnant women.

Results

Among 492 cases of pre-eclampsia, 130 (26.4%) were HIV infected. In the control group, 183/500 (36.6%) were HIV infected (p = 0.001, OR = 0.62, 95% CI: 0.47–0.82). After adjustment to match the difference in maternal age and parity, the rate of HIV/AIDS was lower in the pre-eclamptic group than in the control group (p = 0.005, OR = 0.658).

Conclusion

The rate of HIV/AIDS was significantly lower in women with pre-eclampsia than in normotensive healthy pregnant women.