The impact of structured self-monitoring of blood glucose on glycaemic variability in non-insulin treated type 2 diabetes: The SMBG study,a 12-month randomised controlled trial

Background and AimsThere is inconsistent evidence supporting the self-monitoring of blood glucose (SMBG) in people with non-insulin treated type 2 diabetes (T2D). Structured SMBG protocols have a greater impact on glycaemic control than unstructured SMBG and may improve measures of glycaemic variability (GV), though few previous studies have reported on specific GV outcomes. Our aim was to determine the impact of structured SMBG on simple measures of GV in people with T2D.MethodsParticipants undertook structured SMBG over 12 months, with HbA_1c recorded at baseline and at 3-monthly follow-up. For each participant, the mean blood glucose (MBG), fasting blood glucose (FBG), standard deviation BG (SD-BG), coefficient of variation of BG (CV-BG), mean absolute glucose change (MAG) and HbA_1c were determined for each 3-month period. Responders were participants with an improvement in HbA_1c of ≥5 mmol/mol (0.5%) over 12 months.ResultsData from two hundred and thirty-one participants were included for analysis. Participants had a baseline median [interquartile range] HbA_1c 68.0 [61.5–75.5] mmol/mol (8.4%). Participants demonstrated significant improvements in the MBG (−1.25 mmol/L), FBG (−0.97 mmol/L), SD-BG (−0.44 mmol/L), CV-BG (−1.43%), MAG (−0.97 mmol/L), and HbA_1c (−7.0 mmol/mol) (all p < 0.001) at 12 months compared to these measures collected within the first 3 months of SMBG. Responders had a significantly higher baseline median [interquartile range] HbA_1c of 70.0 [63.0–78.0] mmol/mol compared to 61.0 [56.5–66.0] mmol/mol in non-responders (P < 0.001).ConclusionsStructured SMBG improved all the observed measures of GV. These results support the use of structured SMBG in people with non-insulin treated T2D.     

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.     

Hemoglobin A1c Self-recording in the Management of Diabetes Mellitus: A Pilot Study

HbA_1c evaluates glycemic control 3–6 weeks retrospectively. To achieve improvements in glycemic control we have tested a patient-administered HbA_1c control program in 12 (11 type I) diabetic patients. In the program, HbA_1c was estimated once a month for 12 months and the results were mailed to the patient who recorded them in a specially designed HbA_1c chart. The results in the probands were compared with 24 matched (22 type I) diabetic patients. The results showed that HbA_1c fell significantly (p<0.01) during the year in the probands, from 8.84±1.12% to 7.48±0.95%, and was unchanged in the controls (8.41 ±1.78% and 8.17±1.74%, respectively). Accordingly, HbA_1c self-recording improves glycemic control in diabetic patients.     

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.     

Hemoglobin A1c,comorbid conditions and all-cause mortality in older patients with diabetes: A retrospective 9-year cohort study

AimsTo examine whether hemoglobin A_1c levels and comorbid conditions are related to all-cause mortality in a cohort of patients with type 1 or 2 diabetes receiving continuous care for 9 years. In patients with comorbid congestive heart failure (CHF), we test for ‘reverse epidemiology,’ or whether greater HbA_1c values are associated with lower risk of mortality.MethodsThe population for this longitudinal cohort study was 8820 Group Health enrollees in the Seattle area with type 1 or 2 diabetes in 1997 and enrolled continuously from 1997 to 2006. Comorbid conditions were hypertension, coronary artery disease, congestive heart failure, depression, and chronic pulmonary disease. Mistimed HbA_1c scores were addressed by multiple imputation, and Cox proportional hazards models estimated associations controlling for other risk factors.ResultsAbout 30% of the enrollees died in 1998–2006. CHF had the strongest association with all-cause mortality. Compared to enrollees with HbA_1c ≥ 7.1% (54 mmol/mol) and <7.5% (58 mmol/mol; 5th decile), enrollees with HbA_1c < 6.4% (46 mmol/mol) had a significantly greater risk of death (HR range: 1.28–2.26). HbA_1c > 7.5% had HR < 1.0 but were not significant. For enrollees with diabetes and CHF at baseline, HbA_1c scores ≥ 8.7% (72 mmol/mol) had a significantly lower risk of death (HR range: 0.64–0.69).ConclusionsIn our patient population, HbA_1c scores < 6.4% have significantly higher all-cause mortality. CHF is a major determinant of all-cause mortality. Adults with comorbid CHF and high HbA_1c scores have lower all-cause mortality.     

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.     

Effect of HbA1c combined FPG on screening diabetes in health check-up

ObjectiveTo appraise the effectiveness of HbA_1c and fasting plasma glucose (FPG) on screening diabetes in health check-up.MethodsA total of 1 337 individuals (male 850, female 487), aged 27 to 91 years with HbA_1c test were included. Participates with HbA_1c ?6.0% or FPG?6.1 mmol/L underwent oral glucose tolerance test (OGTT). Diabetes mellitus was diagnosed according to the criteria of WHO in 1999, FPG?7.0 mmol/L and/or OGTT 2 h-postload plasm glucose (2 h-PG)?11.1 mmol/L. The sensitivity and specificity of HbA_1c thresholds and FPG or combination test on screening of diabetes were analyzed.ResultsA total of 842 subjects had HbA_1c <6.0%, in which 32 had isolated FPG?6.1 mmol/L, of 495 had HbA_1c?6.0%. Subjects with HbA_1c?6.0% had significant increased disorder indexes than those with HbA_1c<6.0%. 527 subjects who had HbA_1c?6.0% or FPG?6.1 mmol/L underwent OGTT. A total of 234 subjects were newly diagnosed diabetes, including 123 (123/234, 52.56%) with FPG?7.0 mmol/L, and 111 subjects (111/234, 47.43%) with isolated 2 h-PG?11.1 mmol/L. Among 234 new diabetes, 91.88% (215 subjects) had HbA_1c?6.3%, and 77.40% (181 subjects) had HbA_1c?6.5%. HbA_1c?6.3% combined FPG ?7.0 mmol/L increased the positive rate of newly diagnosed diabetes from 91.88% to 96.58%.ConclusionsHbA_1c is a practical and convenient tool for screening undiagnosed diabetes in routine health check-up of a large population. Combined use of HbA_1c?6.3% and/or FPG?7.0 mmol/L is efficient for early detection of diabetes.     

Differences in HbA1C at the time of diabetes diagnosis in the adult population of Ontario,Canada

AimsTo determine the proportion of adults with HbA_1c ≥ 8.0% (64 mmol/mol) at diabetes diagnosis, as an indicator of delayed diagnosis or less intensive screening.MethodsWe conducted a cross-sectional population-level study using clinical, administrative and immigration data from Ontario, Canada. We identified all individuals diagnosed with diabetes between June 2012 and June 2015, and determined the HbA_1c between 60 days prior to and 30 days after diagnosis. Individuals were stratified based on many sociodemographic, clinical and primary care characteristics, and the proportion with HbA_1c ≥ 8.0% (64 mmol/mol) was determined.ResultsMean HbA_1c at diabetes diagnosis in the population was 7.3 ± 1.9% (56 ± 21 mmol/mol), and 21.1% had HbA_1c ≥ 8.0% (64 mmol/mol) at diagnosis. Factors for which there were important differences in the proportion with HbA_1c ≥ 8.0% (64 mmol/mol) included age, sex, ethnicity, comorbidities, frequency of primary care and primary care rostering.ConclusionsIn a real-world population-level setting, more than one-fifth of individuals diagnosed with diabetes have HbA_1c levels ≥8.0% (64 mmol/mol), suggesting a delay in diagnosis due to inadequate screening. Differences were found based on age, sex and clinical factors, but not based on socioeconomic or immigration factors.     

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.     

Continuous Glucose Monitors: Use of Waveform Versus Glycemic Values in the Improvements of Glucose Control,Quality of Life,and Fear of Hypoglycemia

How patients are benefitting from continuous glucose monitoring (CGM) remains poorly understood. The focus on numerical glucose values persists, even though access to the glucose waveform and rate of change may contribute more to improved control. This pilot study compared outcomes of patients using CGMs with or without access to the numerical values on their CGM. Ten persons with type 1 diabetes, naïve to CGM use, enrolled in a 12-week study. Subjects were randomly assigned to either unmodified CGM receivers, or to CGM receivers that had their numerical values obscured but otherwise functioned normally. HbA_1c, quality of life (QLI-D), and fear of hypoglycemia (HFS) were assessed, at baseline and at week 12. Baseline HbA_1c for the entire group was 7.46 ± 1.27%. At week 12 the experimental group HbA_1c reduction was 1.5 ± 0.9% (p < .05), the control group’s reduction was 0.06 ± 0.61% (p > .05). Repeated measures testing revealed no significant difference in HbA_1c reduction between groups. Both groups had reductions in HFS; these reductions were statistically significant within groups (p < .05), but not between groups. QLI-D indices demonstrated improvements (p < .05) in QLI-D total and the health and family subscales, but not between groups. The results of this pilot study suggest that benefits of CGM extend beyond reductions in HbA_1c to reductions in fear of hypoglycemia and improvements in quality of life. The display of a numerical glucose value did not improve control when compared to numerically blinded units.     

Changes in HbA1c and frequency of measuring HbA1c and adjusting glucose-lowering medications in the 10 years following diagnosis of type 2 diabetes: a population-based study in the UK

Aims/hypothesis

The aim of this work was to study levels of HbA_1c and patterns of adjusting glucose-lowering drugs in patients with impaired glycaemic control over 10 years after diagnosis of type 2 diabetes.

Methods

We studied 4,529 individuals in The Health Improvement Network Database newly diagnosed with type 2 diabetes in the year 2000.

Results

From 6 months to 10 years after diagnosis, the HbA_1c increased from 7.04% (53.4 mmol/mol) to 7.49% (58.3 mmol/mol) (average annual change: 0.047% [0.51 mmol/mol]). The greatest annual change occurred between 6 months and 2 years (0.21% [2.30 mmol/mol] increase per year, p?<?0.001), followed by the 2–5 year time period (0.033% [0.36 mmol/mol] increase per year, p?<?0.001). No significant increase in HbA_1c occurred between 5 and 10 years (p?=?0.20). In multivariable analyses, patients who were younger (p?<?0.001), with higher BMI (p?=?0.033) and who were current insulin users (p?=?0.024) at diagnosis had greater increases in HbA_1c between 6 months and 2 years. For individuals with HbA_1c above 7.0% (53 mmol/mol) the mean time to next measurement of HbA_1c was 0.53 years and increase in doses or changes to other glucose-lowering medications were performed in 26% of cases.

Conclusions/interpretation

HbA_1c increases by approximately 0.5% (5 mmol/mol) over 10 years after diagnosis of type 2 diabetes, with the main increase appearing in the first years after diagnosis. More frequent monitoring of HbA_1c and adjustments of glucose-lowering drugs may be essential to prevent the decline.     

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.     

Relationship between number of contacts between previous dropouts with type 2 diabetes and health care professionals on glycaemic control: A cohort study in public primary health care

AimPrevious study findings have shown that more frequent contacts with the diabetes care team predict better diabetes control. It is unknown whether this is true also for previous dropouts with type 2 diabetes (T2D). The aim of this study was to evaluate if those previous dropouts with T2D who succeeded to improve their glycaemic control had more frequent contacts with health care professionals in the public primary diabetes health care system than those dropouts who did not show improvement.MethodsIn this “real life” retrospective cohort study, we identified 115 dropouts with T2D who were contacted by trained diabetes nurses and who returned to a public T2D-care system. Those previous dropouts who had baseline haemoglobin A_1c ≥53 mmol/mol (7%) and had a reduction in HbA_1c ≥ 6 mmol/mol (0.5%) during the follow-up were compared with those with unsatisfactory change in HbA_1c (baseline HbA_1c ≥ 53 mmol/mol and change <6 mmol/mol, or HbA_1c < 53 mmol/mol at the baseline measurement but above that in the end of the study period) or with those who remained at good glycaemic control over the study period. Trained diabetes nurses collected quantitative data from the patient records about visits and contacts during the follow-up.ResultsPrevious dropouts showing improvement had more visits to the diabetes nurse (p = 0.003) and other nurses (p < 0.001) than those with no improvement or those with satisfactory glycaemic control. Telephone calls not focusing on diabetes (p < 0.001) were also more frequent among previous dropouts with improvement than among the others.ConclusionsEspecially previous dropouts with T2D who had poor glycaemic control, may benefit from more frequent contacts including visits and telephone calls. Recalling dropouts does not seem to lead to overuse of the T2D care-system by those recalled patients whose glycaemic control does not require special care.     

Orlistat 120 mg improves glycaemic control in type 2 diabetic patients with or without concurrent weight loss

Background: Both obesity and type 2 diabetes are associated with increased morbidity and mortality. Published data suggest that orlistat 120 mg, a lipase inhibitor used to treat obesity, may improve glycaemic parameters through weight loss–independent effects. Aim: To investigate the effect of orlistat 120 mg on weight loss, and assess whether changes in glycaemic parameters [fasting plasma glucose (FPG) and haemoglobin A_1c (HbA_1c)] are independent of weight loss. Methods: This retrospective analysis of pooled data from seven multicentre, double‐blind, placebo‐controlled studies involved overweight or obese patients with type 2 diabetes (aged 18–70 years). Patients were required to have a body mass index of 27–43 kg/m², HbA_1c of 6.5 to <13%, and stable weight for ≥3 months. Subjects received orlistat 120 mg tid or placebo for 6 or 12 months. Results: A total of 2550 overweight or obese patients with type 2 diabetes were enrolled and randomized to treatment with orlistat 120 mg tid (n = 1279) or placebo (n = 1271). For the whole population, patients treated with orlistat 120 mg had significantly greater mean decreases in FPG compared with placebo‐treated patients (?1.39 mmol/l vs. ?0.47 mmol/l; p < 0.0001). In addition, orlistat 120 mg provided significantly larger mean decreases in HbA_1c compared with placebo (?0.74% vs. ?0.31%; p < 0.0001). For patients with minimal weight loss (≤1% of baseline body weight), orlistat 120 mg still provided a significantly greater decrease in the least squares mean value for both FPG (?0.83 mmol/l vs. ±0.02 mmol/l; p = 0.0052) and HbA_1c?0.29% vs. ±0.14%; p = 0.0008). This suggested that the improvement of glycaemic control with orlistat 120 mg was independent of weight loss. Using linear regression analysis, improvement in glycaemic control (FPG and HbA_1c) with orlistat 120 mg was less strongly correlated with weight loss than for placebo. Conclusion: Orlistat 120 mg appears to improve glycaemic control more than would be predicted by weight loss alone in overweight or obese patients with type 2 diabetes. Postulated mechanisms underlying this effect include an improvement of insulin sensitivity, a slower and incomplete digestion of dietary fat, reduction of postprandial plasma non‐esterified fatty acids, decreased visceral adipose tissue, and stimulation of glucagon‐like peptide‐1 secretion in the lower small intestine.     

Discordance in the reduction rate between glycated albumin and glycated hemoglobin levels in type 2 diabetes patients receiving SGLT2 inhibitors

AimsAlthough the difference in HbA_1c reduction between sodium-glucose cotransporter 2 (SGLT2) inhibitors and other oral glucose-lowering agents is relatively small, SGLT2 inhibitors exhibit beneficial cardiorenal protection. This study was based on the hypothesis that changes of HbA_1c in patients treated with SGLT2 inhibitors may not accurately reflect an improved glycemic profile.MethodsTwo studies were conducted: 1) a retrospective cohort study of 3039 patients administered with either an SGLT2 or a dipeptidyl peptidase-4 (DPP4) inhibitor for 12 months comparing the changes in glycated albumin (GA) and HbA_1c levels and 2) a pilot study of 10 patients whose glycemic dynamics were evaluated using flash glucose monitoring at baseline and 2 months after treatment with an SGLT2 inhibitor.ResultsSGLT2 inhibitors reduced GA more markedly than HbA_1c in both studies. DPP4 inhibitors decreased both GA and HbA_1c to a comparable degree. The mean glucose levels and glycemic standard deviation were significantly reduced after treatment with an SGLT2 inhibitor, in concordance with GA decline, although the lowering of HbA_1c was marginal.ConclusionsChanges in HbA_1c levels underestimated the glucose-lowering effect and the diminished glycemic fluctuation induced by SGLT2 inhibitors. Thus, the distinct biomarker roles of GA and HbA_1c should be reevaluated.     

Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration

Summary Chromatographically determined haemoglobin A_1c concentration was measured during short-term (1–24 h) changes in glucose concentration in vitro and in vivo. In vitro at 37 °C the HbA_1c concentration increased with glucose concentration and time both in normal and diabetic erythrocytes. In normal erythrocytes incubated in 20–100 mmol/l glucose, the increases in the HbA_1c concentration were maximal after 4–6 h and then stable for the next 18–20 h. During the first hour, increases in the HbA_1c concentration were linear with time and on average 0.034% HbA_1c × h^–1 × mmol/l glucose^–1. In erythrocytes, after a rapidly produced increase (2h), HbA_1c decreased to preincubation concentrations during a further incubation of the erythrocytes in a glucose-free medium at 37 °C for 4–6 h. The mean rate of linear decrease was 0.017% × h^–1 × mmol/l glucose^–1. After incubation of erythrocytes in 100 mmol/l glucose for 24 h, 1.3% HbA_1c remained stable for 6 h in saline. The rapid increase in HbA_1c concentration, as determined by chromatography, was not due to stable HbA_1c (ketoamine linked glucose) as no increase was found in the HbA_1c concentrations determined by the thiobarbiturate method. In juvenile diabetics controlled by an artificial beta-cell, rapid changes of blood glucose concentration (up to 20 mmol/l) resulted in increases in HbA_1c concentration of as much as 1.9% within 12 h (mean 1.1%). Rapid in vivo increases in HbA_1c concentration were reversible by normalization of the blood glucose concentration. That rapid changes in HbA_1c may occur in daily diabetic life was evidenced by differences in HbA_1c concentration between blood samples from out-patient diabetics incubated in saline for 16 hours at 4 °C and 37 °C (range of differences 0.2–1.4% HbA_1c). The differences correlated to the blood glucose concentration at the time of sampling blood for HbA_1c determination. Thus, incubation of blood at a low glucose concentration prior to determination of the glycosylated haemoglobin concentration may overcome interference from rapidly produced HbA_1c.     

Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets - the TITRATETM study

Aims: To compare efficacy and safety of two fasting plasma glucose (FPG) titration targets [4.4–6.1 mmol/l (80–110 mg/dl) and 3.9–5.0 mmol/l (70–90 mg/dl)] using a patient‐directed, treat‐to‐target algorithm for once‐daily basal insulin in insulin‐naïve subjects with type 2 diabetes suboptimally treated with oral antidiabetes drugs (OADs). Methods: In this 20‐week, randomized, controlled, open‐label, multicentre, treat‐to‐target study, 244 insulin‐naïve subjects with type 2 diabetes, HbA_1c≥7.0 and ≤9.0% on OAD treatment, were randomized (1 : 1) to one of two treatment arms using 3.9–5.0 or 4.4–6.1 mmol/l FPG as titration targets. Once‐daily insulin detemir doses were adjusted using algorithm‐guided patient‐directed titration to achieve target FPG values. Results: Overall, the combined treatment groups achieved a mean HbA_1c level of 6.9% at the end of the study. Substantial reductions in HbA_1c were seen in both treatment groups, with the majority of subjects in both titration groups at the end of the study achieving the American Diabetes Association (ADA)‐recommended HbA_1c level of <7%. In the 3.9–5.0 mmol/l FPG target treatment group, HbA_1c values decreased from a baseline mean of 8.0% to 6.8% at 20 weeks. In the 4.4–6.1 mmol/l FPG target group, HbA_1c values decreased from 7.9% at baseline to 7.0% at 20 weeks (Intention to treat ‐ last observation carried forward data set). These decreases were significantly different between the two treatment groups (Least squares mean difference = ?0.271, 95% CI ?0.441 to ?0.101, p = 0.0019), favouring the FPG target of 3.9–5.0 mmol/l vs. the 4.4–6.1 mmol/l target. At the end of the study period, 64.3% of subjects in the 3.9–5.0 mmol/l treatment group achieved HbA_1c levels <7% compared with 54.5% of subjects in the 4.4–6.1 mmol/l group (95% CI 1.03–3.37, odds ratio 1.86, p = 0.04). Insulin detemir dosing patterns were similar between treatment groups, with the 3.9–5.0 mmol/l group using slightly greater doses throughout the study period (0.57 U/kg vs. 0.51 U/kg at the end of the study). Overall rates of hypoglycaemia episodes were low and were comparable between treatment groups (7.73 and 5.27 events/subject/year for the 3.9–5.0 and 4.4–6.1 mmol/l groups, respectively). A single event of major hypoglycaemia was reported in the 3.9–5.0 mmol/l group. Mean weight changes from baseline to the end of the study were small and did not differ significantly between treatment groups. Conclusions: The 3.9–5.0 mmol/l FPG target showed superior efficacy compared with the 4.4–6.1 mmol/l target, although both FPG titration targets resulted in substantial reductions of HbA_1c in patients with type 2 diabetes using a patient‐directed insulin titration algorithm. A majority of subjects in both titration groups achieved the ADA‐recommended guideline of <7% HbA_1c at the end of the study with low rates of hypoglycaemia. These data indicate that lowering the fasting glucose target using a self‐directed titration algorithm with once‐daily detemir is safe and increases the likelihood of achieving the target level of HbA_1c. Indeed, using this approach, a majority of patients can achieve an HbA_1c of <7%.     

Staged diabetes management according to individual patient insulin resistance and beta-cell function ameliorates glycaemic control in type 2 diabetes mellitus

Objective The current consensus algorithm for management of type 2 diabetes is based on the fasting glucose concentration and glycated haemoglobin A_1c (HbA_1c) level. We applied a new therapeutic strategy by assessing insulin secretion and insulin resistance, in addition to glucose concentrations in individual patients. Design and patients We enrolled 193 patients with type 2 diabetes. The patients were assigned to one of six groups according to insulin secretion measured by the serum fasting C‐peptide concentration and insulin resistance measured by an insulin tolerance test (ITT). The two groups were treated differently: 108 patients were treated using a new staged diabetes management (SDM) strategy and 85 patients continued with conventional therapy. Measurements We compared metabolic variables in the two groups at baseline and 12 months after enrolment. Results In patients treated with the SDM strategy, fasting glucose concentration decreased from 9·8 ± 2·1 to 8·2 ± 1·7 mmol/l (P < 0·001). Postprandial 2‐h glucose concentration decreased from 14·19 ± 3·34 to 12·27 ± 3·24 mmol/l (P < 0·001). HbA_1c level decreased from 8·37 ± 1·42% to 7·72 ± 1·39% (P < 0·001). About 43% of the new SDM group achieved an HbA_1c of < 7·0% compared with 25% of patients in the conventional treatment group. Conclusions The new SDM strategy, based on individual data on insulin resistance and insulin secretion, may provide valuable clinical benefits in non‐obese Korean patients with type 2 diabetes.     

Multidisciplinary approach to patients with poorly controlled type 2 diabetes mellitus: a prospective,randomized study

Abstract. Practicing physicians as well as diabetes specialists are confronted with the often-frustrating experience of dealing with patients with poorly controlled diabetes. It is not always obvious why these patients fail to improve. The aims of this study were two-fold: (a) to determine if the interdisciplinary approach offered by the Western Negev Mobile Clinic Diabetes Program (WNMDCP) is of benefit in patients with poorly controlled type 2 diabetes and (b) to more fully characterize patients refractory to treatment. Two primary-care clinics of the Western Negev were randomly selected as control and intervention. All patients from both clinics with hemoglobin (HbA_1C) 10% (tested during June-July 2000) were studied for 6 months. Patients from the control clinic continued the usual treatment. Patients from the intervention clinic received the interdisciplinary approach offered by WNMCDP. The rate of improvement of diabetes control, measured as a decrease in HbA_1C values of at least 0.5%, and compliance to treatment were determined. Overall, 48 of 258 patients in the intervention clinic and 34 of 179 patients in the control clinic met the inclusion criteria. At the 6-month follow-up, we observed significant improvements in plasma glucose (-1.5 mmol/l; p=0.003) and HbA_1C (-1.8%; p=0.00001) in the intervention group but not in the control group. The compliance and response rates were 85% and 71% for the intervention group and 32% and 35% for the control group, respectively. Patients from the intervention clinic showed significant improvement in the endpoints compared to patients from the control clinic. More than 70% of patients with poorly controlled diabetes mellitus responded to the interdisciplinary treatment approach offered by WNMDCP. The group of non-responders comprised patients with poor compliance (15%) and those with serious concomitant diseases or limitations of mobility.