Estimates of the relative and absolute diurnal contributions of fasting and post-prandial plasma glucose over a range of hyperglycaemia in type 2 diabetes

AimsTo re-examine the relative and absolute contributions of fasting/pre-prandial glucose (FPG) and post-prandial glucose (PPG) to 24-h hyperglycaemia and HbA_1c respectively in non-insulin treated subjects with type 2 diabetes (T2DM).Materials and methodsA total of 52 T2DM subjects (37 men) had daytime 12 h plasma glucose (PG) profiles determined in response to three serial identical test meals commencing at 08 00 h with pre-prandial and frequent post-prandial blood samples collected. The overnight PG profile was derived by projecting the 20 00 h glucose concentration to the pre-breakfast value at 08 00 h. PPG exposure was calculated above fasting/pre-prandial value for each meal. Excess hyperglycaemia was calculated based on a PG > 5.5 mmol/L with fasting hyperglycaemia being the difference between the two measurements. The subjects were divided into five groups according to the HbA_1c (Group 1 < 7.0%; Group 2: 7.0– < 7.5; Group 3: 7.5– < 8.0%; Group 4: 8.0– < 9.0%; Group 5: ≥ 9.0%). The 24 h relative contribution of PPG exposure and fasting hyperglycaemia to excess hyperglycaemia and the absolute contribution of PPG and fasting hyperglycaemia to excess HbA_1c (HbA_1c – 5.1%) was calculated.ResultsWith deteriorating glycaemia, the relative contribution of PPG exposure decreased across the groups from 43.5% (HbA_1c < 7.0%) to 17.8% (HbA_1c ≥ 9.0%), whilst the contributions of fasting hyperglycaemia increased from 56.5% to 82.2% (P = 0.004), respectively. The absolute contributions of PPG to excess HbA_1c was 0.7%, which remained relatively stable across the spectrum of HbA_1c, whilst fasting hyperglycaemia increased significantly from groups 1 to 5 (P < 0.001).ConclusionsFasting hyperglycaemia contributes substantially in all groups, increasing as HbA_1c deteriorates. The absolute contribution of PPG to excess HbA_1c did not vary across the range of HbA_1c, representing a significant relative contribution even in well-controlled subjects with a HbA_1c < 7.0%.     

Characteristics of newly diagnosed adults with type 1 diabetes in the UK and evolution of glycaemic control,body mass index and Charlson comorbidity index over the first 5 years after diagnosis

AimsThis retrospective, longitudinal study characterised 2430 adults (mean age 40.8 ± 16.1 years) with newly diagnosed type 1 diabetes (T1D) over the first 5 years of insulin treatment.MethodsData from 1 year pre- and up to 5 years post-insulin initiation were extracted from the UK Clinical Practice Research Datalink (1990–2013). Baseline HbA_1c, BMI and Charlson comorbidity index (CCI) score were compared with data at 1, 2, 3 and 5 years.ResultsMean HbA_1c decreased significantly from baseline 95 ± 32.8 mmol/mol (10.8 ± 3.0%) to 61 ± 21.9 mmol/mol (7.7 ± 2.0%) at 1 year, remaining significantly lower at 2, 3 and 5 years (p < 0.0001). One year after initiating insulin, only 6.3% of patients had HbA_1c <48 mmol/mol (<6.5%). There was no further improvement in HbA1c after 1 year. Mean BMI increased significantly from baseline 25.3 ± 5.5 kg/m² to 27.2 ± 5.8 kg/m² at 1 year; p < 0.0001), remaining significantly higher thereafter, with over two-thirds having overweight/obesity by year 5. Mean CCI score increased significantly (1.32, baseline; 1.46, year 1; 1.75, year 5). CCI patterns were similar within BMI and HbA_1c strata.ConclusionsMore intensive support to reach and maintain glycaemic targets soon post-diagnosis, while avoiding weight gain, and prevention and optimal management of comorbidities are warranted.     

Patients newly diagnosed with clinical type 2 diabetes mellitus but presenting with HbA1c within normal range: 19-Year mortality and clinical outcomes

AimsTo investigate whether long-term mortality or clinical outcomes differed between patients diagnosed with type 2 diabetes mellitus and presenting with HbA_1c within or above normal range at time of diagnosis.MethodsData were from a population-based sample of 1136 individuals with newly diagnosed type 2 diabetes mellitus. The diagnosis was confirmed with a single fasting whole blood/plasma glucose ≥7.0/8.0 mmol/l. The median time from day of diagnosis until end of follow up was 18.8 years. Patients were grouped according to normal HbA_1c and elevated HbA_1c at diagnosis. The effect of elevated HbA_1c on a number of clinical outcomes and all-cause mortality was assessed in Cox regression models.ResultsAt diagnosis, 97 patients (8.5%) had an HbA_1c level within normal range. Age (mean (SD)) at diagnosis was 64.5 (11.5) years. Both unadjusted and adjusted hazard ratios for the effect of HbA_1c on mortality and other outcomes were not statistically significant.ConclusionsPatients who are diagnosed with type 2 diabetes mellitus by means of elevated fasting whole blood/plasma glucose but have HbA_1c within reference range at diagnosis do not seem to have a relatively benign long-term clinical course. Therefore new diagnostic procedures should preferably be able to identify these individuals.     

Impact of postprandial and fasting glucose concentrations on HbA1c in patients with type 2 diabetes

AimThis study aimed to assess the relative contributions of postprandial and fasting glucose concentrations to overall hyperglycaemia.MethodsPatients with type 2 diabetes (n = 973) carried out self-monitored blood glucose (SMBG) profiles on entry into the European Exenatide (EUREXA) trial. Glucose area under the curve was calculated for postprandial excursions (AUC_ppg) and total daytime concentrations > 6.1 mmol/L (AUC_total), as well as for the percentage of glycaemia due to postprandial excursions (%_ppg). In addition, OGTT scores were assessed for each patient. Results were evaluated according to defined HbA_1c categories.ResultsThere was a significant linear relationship between HbA_1c and the derived variables of AUC_ppg, AUC_total and %_ppg (P < 0.001 for each), with explained variance greatest for AUC_total (r² = 37.4%). AUC_ppg increased only slightly up to an HbA_1c of 7.0%, but showed a steeper increase in higher HbA_1c categories. Also, the increase in AUC_total with increasing HbA_1c was much more pronounced. As a result, the postprandial glucose excursion as a proportion of total glucose (%_ppg) decreased across HbA_1c categories from 61.0% at HbA_1c < 6.5% to 22.0% at HbA_1c ≥ 9.0%. HOMA-IR remained virtually unchanged through all HbA_1c categories, while HOMA-B showed no large changes up to HbA_1c 7.0%, but then decreased at higher HbA_1c values. The ΔI30/ΔG30 ratio decreased in the HbA_1c 7.0–7.9% category, but did not change greatly at higher HbA_1c categories.ConclusionWith increasing HbA_1c, there was a decrease in the contribution of postprandial hyperglycaemia to total glycaemia, and fasting hyperglycaemia became more important. This is consistent with impaired insulin release, particularly first-phase release, at higher HbA_1c levels.     

A systematic review and meta-analysis of exercise interventions in adults with type 1 diabetes

AimsConflicting evidence exists regarding the benefits of physical activity for long-term blood glucose control in adults with type 1 diabetes (T1D). The object of this systematic review was to determine the effects of physical activity on long-term blood glucose control in T1D adults.MethodsPubMed/Medline, Embase, CENTRAL, SPORTdiscus, Global Health and ICTRP were searched up to October 2013 for randomized trials of aerobic or resistance exercise training in T1D adults. Exercises had to be performed at least twice weekly for a minimum of two months. The primary outcome was glycated hemoglobin (HbA_1c). Secondary outcomes included cardiorespiratory fitness and insulin dose.ResultsSix randomized trials were identified (323 adults); sample sizes ranged from n = 6 to n = 148 participants receiving the intervention. Five trials had an unknown risk of bias; one trial was deemed to be at high risk of bias. Exercise frequency varied from twice weekly to daily, with intensities (50–90% VO_2peak), and session durations (20–120 min) varying widely. Four trials reported HbA_1c, which decreased with exercise training (mean difference [MD] −0.78% (−9 mmol/mol), 95% CI −1.14 (−13 mmol/mol) to −0.41 (−5 mmol/mol); p < 0.0001; I² 0%) compared with controls. Exercise training improved cardiorespiratory fitness by 3.45 ml/kg/min (95% CI 0.59 to 6.31, p = 0.02, I² 0%) compared with controls. One trial reported an effect on insulin dose (MD −0.4 U/kg, 95% CI −0.53 to −0.27, p < 0.00001) compared to controls.ConclusionThere are currently insufficient well-designed studies to ascertain the true effect of exercise training on HbA_1c in individuals with T1D, but current results are promising.     

Self-titration of biphasic insulin aspart 30/70 improves glycaemic control and allows easy intensification in a Dutch clinical practice

AimsThis 18-month study assessed the improvement in glycaemic control and proportion of patients reaching glycated haemoglobin (HbA_1c) targets with biphasic insulin aspart 30/70 (BIAsp 30) in clinical practice.MethodsType-2 diabetes patients failing on oral antidiabetic drugs (n = 90) or existing insulin regimens (n = 59) started or switched to BIAsp 30. Thiazolidinediones were stopped, metformin was continued. BIAsp 30 was given once daily (n = 41), twice daily (n = 96), or three times daily (n = 12). Patients were taught self-monitoring and self-titration using an algorithm, adding daily doses of BIAsp 30 when necessary.ResultsMean baseline HbA_1c was 8.4%, weight 85.4 kg, and age 57.9 years. All patients experienced significant reductions in HbA_1c (mean 1.9% ± 0.1), fasting plasma glucose (mean 2.8 mmol/l), and post-prandial glycaemia (mean 2.9 mmol/l); 91% of patients achieved HbA_1c < 7% and 52% achieved HbA_1c ≤ 6.5%. No major or nocturnal hypoglycaemia were reported; 15% of patients reported minor hypoglycaemia. Insulin-naïve patients gained mean 2.7 kg; patients who switched from another insulin lost weight (mean ?0.6 kg).ConclusionThe results from this study from routine care suggest that BIAsp 30 may allow a large proportion of type-2 diabetes patients (90%) to improve glycaemic control and reach target HbA_1c < 7%, using self-titration.     

Glycosylated hemoglobin and the risk of death and cardiovascular mortality in the elderly

Background and aimsGlycosylated hemoglobin (HbA_1c) has been associated with incident cardiovascular disease (CVD), but the findings are inconsistent. We tested the hypothesis that HbA_1c may be associated with an increased risk of death and cardiovascular mortality in older adults.Methods and resultsWe evaluated the association between HbA_1c with all-cause and cardiovascular mortality in 810 participants without a history of diabetes in a sub-study of the Cardiovascular Health Study (CHS), a community cohort study of individuals ≥65 years of age. Glycosylated hemoglobin was measured at baseline and all-cause and cardiovascular mortality was assessed during the follow-up period. The relation between baseline HbA_1c and death was evaluated with multivariate Cox proportional hazards regression models. After a median follow-up of 14.2 years, 416 deaths were observed. The crude incidence rates of all-cause mortality across HbA_1c groups were: 4.4% per year, 4.3% per year and 4.6% per year for tertile 1 (≤5.6%), tertile 2 (5.61–6.20%) and tertile 3 (≥6.21%), respectively. In unadjusted and fully adjusted analyses, baseline HbA_1c was not associated with all-cause mortality and cardiovascular mortality (hazard ratio: 1.16 [95% confidence interval 0.91–1.47] and hazard ratio: 1.31 [95% confidence interval 0.90–1.93], respectively for the highest HbA_1c tertile compared with the lowest).ConclusionThese results suggest that HbA_1c does not significantly predict all-cause and cardiovascular mortality in non-diabetic community-dwelling older adults.     

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes

AimsTo evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA_1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes.MethodsThis post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA_1c of < 7.0% (< 53 mmol/mol) per baseline HbA_1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia.ResultsPatients had comparable demographic characteristics and similar HbA_1c and FHG values at baseline in each HbA_1c quartile regardless of whether they reached the target HbA_1c. The higher the HbA_1c quartile, the greater was the decrease in HbA_1c, but also the smaller the percentage of patients achieving the target HbA_1c. HbA_1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA_1c quartiles with either insulin treatment. Patients not achieving the target HbA_1c had slightly higher insulin doses, but lower total hypoglycaemia rates.ConclusionSmaller decreases in FHG were associated with not reaching the target HbA_1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens.     

A large proportion of prediabetes and diabetes goes undiagnosed when only fasting plasma glucose and/or HbA1c are measured in overweight or obese patients

AimsThe purposes of the study were to determine the prevalence of unrecognized dysglycaemia in overweight (body mass index [BMI] 25–29.9 kg/m²) and obese (BMI ≥30 kg/m²) patients, to assess the extent to which measures of fasting plasma glucose (FPG) and/or HbA_1c, compared with oral glucose tolerance tests (OGTTs), misdiagnose dysglycaemia, and to determine the factors associated with an isolated abnormal post-OGTT glucose value.MethodsOGTT was performed and HbA_1c was measured in 1283 inpatients with BMI scores ≥25 kg/m² and no history of dysglycaemia.ResultsPrediabetes was found in 257 (20.0%) subjects (197 with impaired glucose tolerance, 29 with impaired fasting glucose, 31 with both) and diabetes in 77 (6.0%), including 22 with FPG ≥7 mmol/L (WHO definition). The sensitivity of FPG >6 mmol/L, FPG >5.5 mmol/L, HbA_1c ≥6% and the recommendations of the French National Agency of Accreditation and Evaluation in Health Care (ANAES) to identify patients with abnormal OGTTs was 29.9, 41.3, 36.8 and 15.6%, respectively. The factors that were independently associated with diabetes in obese women with FPG <7 mmol/L were age (per 10 years: OR 1.54 [1.00–2.11]; P = 0.049) and FPG (OR 6.1 [1.4–30.0]; P = 0.014), whereas age (OR 1.26 [1.09–1.44]; P < 0.01) and waist circumference (per 10 cm: OR 1.17 [1.01–1.33]; P < 0.05) were independently associated with dysglycaemia in obese women with FPG <6.1 mmol/L.ConclusionIn overweight and obese patients: dysglycaemia is commonly seen; FPG alone, compared with OGTT, failed to diagnose 70% of dysglycaemia cases; FPG >5.5 mmol/L and HbA_1c ≥6.0% are not necessarily substitutes for OGTT; and older age and larger waist circumference should be used to select those obese women with normal FPG who might further benefit from OGTTs to diagnose dysglycaemia.     

Efficacy and safety of sitagliptin added to ongoing metformin and pioglitazone combination therapy in a randomized,placebo-controlled, 26-week trial in patients with type 2 diabetes

AimsTo assess efficacy and safety of sitagliptin, a dipeptidyl peptidase-4 inhibitor, in combination therapy with metformin (≥ 1500 mg/day) and pioglitazone (≥ 30 mg/day) in patients with type 2 diabetes (T2DM) with inadequate glycemic control (hemoglobin A_1c [HbA_1c] ≥ 7.5% and ≤ 11%).MethodsThis placebo-controlled, double-blind study included 313 patients, mean baseline HbA_1c = 8.7%, who were randomized to receive sitagliptin 100 mg/day or placebo for 26 weeks.ResultsThe addition of sitagliptin led to significant (P < .001) mean changes from baseline relative to placebo in HbA_1c (? 0.7%), fasting plasma glucose (? 1.0 mmol/L), and 2-h post-meal glucose (? 2.2 mmol/L). In patients with baseline HbA_1c ≥ 9.0%, mean changes from baseline in HbA_1c were ? 1.6% and ? 0.8% for the sitagliptin and placebo groups, respectively (between-group difference ?0.8%; P < .001). The incidences of reported adverse events were generally similar between the treatment groups. Incidences of symptomatic hypoglycemia were 7/157 [4.5%] and 6/156 [3.8%] in the sitagliptin and placebo groups, respectively (P = .786). Two patients, both in the placebo group, experienced an episode of hypoglycemia that required non-medical assistance.ConclusionsIn this 26-week study, addition of sitagliptin to combination therapy with metformin and pioglitazone improved glycemic control and was generally well tolerated.     

The association between intensive glycemic control and vascular complications in type 2 diabetes mellitus: A meta-analysis

Background and AimIn patients with type 2 diabetes mellitus, the relationship between lowering glycated hemoglobin (HbA_1c) and macrovascular complications is not clear and therefore lowering the level of HbA_1c is controversial.Methods and ResultsWe searched for all randomized controlled trials comparing the effects of intensive and standard glycemic control on vascular events in patients with type 2 diabetes mellitus. The primary endpoint was combined macrovascular complications, including cardiac events, stroke and peripheral vascular disease. Fixed and random effect models were used to analyze the results.Eight studies were included according to selection criteria. The results showed no benefits of intensive glycemic control on macrovascular and microvascular complications (P > 0.1), but a higher rate of severe hypoglycemia (P < 0.00001) in the intensive control group when the target HbA_1c level was <7.0%. When the target HbA_1c level was lowered to 7.0–7.9%, intensive glycemic control showed benefits on the reduction of microvascular events (P < 0.05) without increasing the risk of severe hypoglycemia (P = 0.74), but no influence on macrovascular complications (P > 0.1).ConclusionThe results of this analysis suggest that a target HbA_1c level of 7.0–7.9% may be a better glycemic control target than that of <7.0% in patients with established type 2 diabetes mellitus.     

Retrospective cohort study evaluating exenatide twice daily and long-acting insulin analogs in a Veterans Health Administration population with type 2 diabetes

AimThis was a retrospective cohort study that evaluated the differences in glycated haemoglobin (HbA_1c) and body mass index (BMI) in veterans with type 2 diabetes mellitus (T2DM), prescribed exenatide twice daily (BID) versus long-acting insulin analog (LAIA) two years after initiation in the United States (US) veteran population.Materials and methodsPatients were included if they were ≥ 18 years old with T2DM, and initiated exenatide BID or LAIA at the Veterans Health Administration between January 1, 2006 and December 31, 2010. Multivariate models were used to evaluate the changes in HbA_1c and BMI between groups, controlling for potential confounders. Logistic regression was used to evaluate the odds of achieving ≥ 0.5% HbA_1c reduction based on baseline HbA_1c stratifications: low, < 7%; moderate, 7% to < 9%; and high, ≥ 9%.ResultsA total of 446 exenatide BID and 51,531 LAIA patients met inclusion/exclusion criteria. On average, exenatide BID patients were significantly older (64 versus 60 years) with a higher BMI (37.8 versus 32.9 kg/m²). Baseline HbA_1c was 8.2% and 8.8% for exenatide BID and LAIA patients, respectively (P < 0.001); otherwise, patients were similar for all other characteristics. Exenatide BID treatment was significantly associated with a 0.32% (95%CI: 0.18–0.47%) greater reduction in HbA_1c at two years compared with LAIA. Similar findings were observed for BMI reduction (0.68 kg/m²; 95%CI: 0.42–0.95 kg/m²). Exenatide BID patients with moderate baseline HbA_1c had significantly higher odds of achieving ≥ 0.5% HbA_1c reduction compared with LAIA patients (OR = 1.5; 95%CI: 1.2–2.0).ConclusionsVeterans treated with exenatide BID had significantly greater reduction in HbA_1c and BMI compared with patients treated with LAIA patients two years after initiation.     

Haemoglobin glycation may partly explain the discordance between HbA1c measurement and oral glucose tolerance test to diagnose dysglycaemia in overweight/obese subjects

AimThis study assessed whether the poor correlation between HbA_1c and oral glucose tolerance test (OGTT) for dysglycaemia diagnosis may be explained by haemoglobin glycation (HbG).MethodsA total of 1033 consecutive overweight or obese patients with no known diabetes underwent OGTT and measurement of HbA_1c to diagnose diabetes and dysglycaemia (American Diabetes Association criteria). For each OGTT result category, low, medium and high HbG was defined according to the mean HbA_1c/fructosamine ratio and mean fructosamine. High HbG was defined as values greater than mean values in each OGTT category for both HbA_1c/fructosamine ratio and fructosamine levels, and low HbG was defined as lower values of both. The remaining patients were considered medium HbG.ResultsBased on OGTT and HbA_1c values, 267 (25.8%) and 443 (42.8%) patients had intermediate hyperglycaemia, and 66 (6.4%) and 95 (9.2%) patients had diabetes, respectively. The results were discordant for intermediate hyperglycaemia or diabetes diagnosis in 41.7% and for diabetes diagnosis in 10.0% of the patients. The proportion of patients with HbA_1c ≥ 6.5%, but without OGTT-diagnosed diabetes, was 0%, 3.8% and 32.8% in the low-HbG, medium-HbG and high-HbG groups, respectively. In contrast, the proportion of patients with HbA_1c < 5.7%, but with an abnormal OGTT, was 30.4%, 11.1% and 0%, respectively. The AUROC of HbA_1c to detect OGTT-diagnosed diabetes was better in the medium-HbG group [0.874 (0.816–0.931)] than in those with low or high HbG [0.628 (0.489–0.768); P < 0.01]. Only age was independently associated with high-HbG status [10-year OR: 1.3 (1.1–1.5); P < 0.0001].ConclusionHaemoglobin glycation may explain many of the discordant results between HbA_1c and OGTT when used for dysglycaemia diagnosis.     

Type 2 diabetes care in North Karelia Finland: Do area-level socio-economic factors affect processes and outcomes?

AimsThis research assessed the impact of area-level socio-economic factors on the prevalence and outcomes of type 2 diabetes in North Karelia, Finland.MethodsAll type 2 diabetes patients (n = 10,204) were analyzed from the regional electronic patient database during the years 2011 and 2012. The patient's individual laboratory data was used to assess whether hemoglobin A_1c (HbA_1c) was measured and whether the recommended level of HbA_1c <7% (<53 mmol/l) was achieved. The variables describing socio-economic characteristics of postal code areas were retrieved from the database of Statistics Finland. Linear and logistic regression analyses were used to determine associations.ResultsHbA_1c had been measured in 83% of patients. Over 70% of those with HbA_1c measured reached the recommended level of HbA_1c. The worse the area-level socio-economic status, the more probably HbA_1c was not measured. Achieving the recommended HbA_1c level was associated with being female and having a better area-level socio-economic status. The age-adjusted prevalence of type 2 diabetes was not linearly dependent on the socio-economic circumstances of the postal code areas.ConclusionsThis study shows that socio-economic factors at the small area-level are associated with treatment outcomes. The information from the regional electronic patient database linked with area-level socio-economic information could be effectively utilized to improve diabetes care.     

Racial differences in HbA1c: A cross-sectional analysis of a Brazilian public primary care population

BackgroundBlacks show higher levels of HbA_1c in studies with different populations and are disproportionately affected by most diabetes-related complications.AimsThe study aims to investigate if the prevalence of altered glycated hemoglobin (HbA_1c) varies with skin color and if there is a familial aggregation of either skin color and HbA_1c.MethodsThe study used the CAMELIA study (Cardio-Metabolic-Renal familiar) population, conducted between June 2006 and December 2007 (cross sectional). Families were recruited from 13 Family Doctor Program Unities of Niteroi, Brazil, a highly miscegenated population. The visits included questionnaire, medical consultation, anthropometric and nutritional assessment. Blood pressure, blood/urine samples were collected. The dosage of HbA_1c was performed by immunoturbidimetry in Labmax 240 equipment.ResultsWe compare data of 241 (25.5%) Blacks, versus 422 (44.7%) Mulattos or 272 (28.8%) Whites. The groups did not differ significantly with regard to most measures. Blacks had the lowest levels of income/education, higher frequency of diabetes and hypertension (p < 0.20) as higher levels of HbA_1c (p < 0.05) that persisted after adjusting for possible confounders. Among blacks, the correlations between siblings of HbA_1c were higher than among white/mulatto, reaching 86% versus 50%, respectively.ConclusionThose results indicate that Brazilian Blacks patients must have more attention, focusing on diabetes preventive care. Longitudinal studies are needed to address the question if the altered level of HbA_1c has a real clinical impact.     

Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients

AimRecent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA_1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA_1c target and the occurrence of major clinical events under real-life conditions.MethodsThe T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged > 65 years. The recommended personalized HbA_1c targets were < 7%, < 8% and < 9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses.ResultsOf the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA_1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA_1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69–1.31; P = 0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40–1.94; P = 0.75), 1.14 (95% CI: 0.7–1.83; P = 0.59) and 0.84 (95% CI: 0.60–1.18; P = 0.32), respectively.ConclusionOver a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA_1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.     

Frequency and awareness of hypoglycemia in patients with Type 2 Diabetes treated with two or more insulin injections in primary care outpatient clinics

AimsTo assess the frequency of hypoglycemia events, patient characteristics and the prevalence of impaired awareness of hypoglycemia (IAH) in patients with Type 2 Diabetes (T2D) using two or more insulin injections in primary care.MethodsCross-sectional study performed at 9 Primary Care Centers including review of electronic medical records and an on-site visit to patients using >2 insulin injections with suboptimal control. Episodes of severe hypoglycemia (SH) in the last 12 months were recorded. Non-severe hypoglycemia (NSH) was considered as self-monitoring blood glucose <70 mg/dl. IAH was evaluated and HbA_1c was obtained.Results157 subjects were included (age 68.4 + 10.7 years, 82 women, T2D duration 18.3 + 8.7 years). 57% used multiple daily injections. Total insulin was 66.9 + 43.4 units/day. The mean HbA_1c was 9.2 ± 1.4% (77 ± 12 mmol/mol) and only 13.4% had HbA_1c <8% (64 mmol/mol). The frequency of NSH was 0.74 ± 1.37 episodes/week. Only one patient had a SH the last 12 months. Around 10–12% of patients had IAH. In comparison with normal awareness, those with IAH had a longer duration of T2D (25.3 ± 11.6 vs. 16.1 ± 8.2 years, respectively, p < 0.01). In the multiple linear regression analysis, only the IAH score and the total insulin dose independently determined the NSH number.ConclusionsNSH/SH in patients with T2D treated with two or more insulin injections in primary care settings seems to be relatively common. Although hypoglycemia awareness is predominantly preserved, the presence of IAH should not be ignored as it increases the risk of hypoglycemia and constitutes an additional barrier to recognize and address this burden in T2D.     

Switch from metformin monotherapy to bitherapy with metformin and repaglinide to achieve glycated haemoglobin target in type 2 diabetes (REPAMET Study)

AimTo evaluate glycaemic control, including HbA_1c, following the addition of repaglinide to monotherapy with metformin as part of routine follow-up of adult type 2 diabetes patients no longer controlled with metformin (i.e. in secondary monotherapy failure).Subjects and methodsProspective, open-label, observational study in primary care setting, consisting of 2 visits (metformin/repaglinide bitherapy initiation and follow-up within 10–20 weeks), with analysis of HbA_1c levels, fasting glycaemia, body mass index and hypoglycaemic episodes within past month.Results2171 patients were included, with average diabetes duration (mean ± 1 SD) 7 ± 6 years, BMI 30.2 ± 5.5 kg/m², and fasting glucose at entry 179 ± 50 mg/dl. Mean decrements in fasting glycaemia and HbA_1c between visits rose with increasing HbA_1c at Visit 1. The proportion of patients with controlled fasting glycaemia increased by an absolute 40% for therapeutic goal set at 90–130 mg/dl. Treatment goal (HbA_1c < 7.0%) was achieved by 38% of patients at Visit 2, with number of patients with HbA_1c ≥ 8.0% decreasing by an absolute 34%. The percentage of patients experiencing ≥1 hypoglycaemic episode(s) within the previous month marginally rose from 5.0 to 5.6%.ConclusionCombining metformin with repaglinide appears a safe and effective therapeutic option once monotherapy with metformin is no longer adequate in adult patients with type 2 diabetes followed in a primary care setting.     

Evaluation of the In2it® analyzer for HbA1c determination

AimThe prominent role of HbA_1c in the follow-up of glycaemic balance in patients with diabetes mellitus necessitates the use of robust and reliable methods of assay. The purpose of this study was to evaluate the In2it^® analyzer, a new device allowing HbA_1c evaluation within 10 min, using 10 μL of blood, in the laboratory or clinical unit, using an affinity-based method.MethodsThe analytical performance of the In2it^® analyzer was tested for precision, interference and linearity, and correlated with two other analyzers – the high-performance liquid chromatography (HPLC)-based Variant II™ analyzer in a laboratory, and the immunology-based DCA 2000^® analyzer in a clinical unit – for practicability and its compliance with good laboratory practices.ResultsHbA_1c assay is linear from 4 to 14%, with coefficients of variations ranging from 2.4 to 3.9%. In2it^® correlation was satisfactory with both the HPLC Variant II^® (r² = 0.974, P < 0.001) and DCA 2000^® (r² = 0.794, P < 0.001) analyzers although, with the latter, unpredictable differences were randomly observed. However, the method is free of interference from common haemoglobin variants, labile glycated haemoglobin and carbamylated haemoglobin, hyperbilirubinaemia (< 520 μmol/L) and hypertriglyceridaemia (< 6 mmol/L). The practicability of the analyzer is good. However, software specifications need to be upgraded, especially for quality-control management, traceability of results and data safety.ConclusionThe In2it^® analyzer is suitable for HbA_1c assay in small laboratory series and for point-of-care testing, and its analytical performance is satisfactory overall. However, several issues related to software need to be improved for optimal application. Also, special attention should be paid concerning the possibility of underestimation of results in cases of high hypertriglyceridaemia.     

Impact of elective hospital admissions on glycaemic control in adolescents with poorly controlled type 1 diabetes

AimDifferent treatment strategies have been used to manage adolescents with poorly controlled type 1 diabetes. We investigated whether a brief elective hospital admission improves haemoglobin A_1c (HbA_1c) over 12 months.MethodsWe studied a retrospective cohort of adolescents with poorly controlled type 1 diabetes attending a tertiary care pediatric diabetes clinic in Montreal, Canada, between January 2005 and December 2010. Hospitalized adolescents (admitted group) were matched with controls (non-admitted group) for age and baseline HbA_1c. HbA_1c values at baseline, 6 and 12 months were obtained from the clinic database.ResultsThirty patients aged 11 to 17 years with a first elective admission for poor metabolic control were paired with 30 non-admitted patients. At baseline, HbA_1c was 12.2 ± 1.6% in admitted and 12.0 ± 1.2% in non-admitted patients. There were no clinically important differences in potential confounders between groups. There was no improvement in the primary outcome as assessed by the change in HbA_1c at 12 months in the admitted group (–1.3 ± 2.3%) compared with the non-admitted group (–2.1 ± 1.7%) (P = 0.078). No improvement in intermediary measures of glycaemic control was observed (HbA_1c at 6 months or change at 6 months). After 12 months, HbA_1c values were higher in the admitted group (10.9 ± 1.9%) versus the non-admitted group (9.9 ± 1.4%) (P = 0.016).ConclusionElective hospital admission for adolescents with poorly controlled type 1 diabetes does not seem to be an effective strategy to improve HbA_1c over 12 months.