Pilot trial of diabetes self-management education in the hospital setting

AimsDiabetes self-management education (DSME) is recommended for all patients with diabetes. Current estimates indicate that <50% of patients receive DSME, increasing risk for hospitalization which occurs more frequently with diabetes. Hospitalization presents opportunities to provide DSME, potentially decreasing readmissions. To address this, we investigated the feasibility of providing DSME to inpatients with diabetes.MethodsPatients hospitalized on four medicine units were randomized to receive DSME (Education Group) (n = 9) prescribed by a certified diabetes educator and delivered by a registered nurse, or Usual Care (n = 12). Participants completed Diabetes Knowledge Tests (DKT), Medical Outcomes Short Form (SF-36), Diabetes Treatment Satisfaction Questionnaire (DTSQ), and the DTSQ-inpatient (DTSQ-IP). Bedside capillary blood glucoses (CBG) on day of admission, randomization and discharge were compared.ResultsThere were no group differences in demographics, diabetes treatment, admission CBG (186 ± 93 mg/dL vs. 219 ± 84 mg/dL, p = 0.40), DKT scores (Education vs. Usual Care 48 ± 25 vs. 68 ± 19, p = 0.09), SF-36, and DTSQ scores (28 ± 6 vs. 25 ± 7, p = 0.41). Patients receiving education reported more satisfaction with inpatient treatment (83 ± 13 vs. 65 ± 19, p = 0.03), less hyperglycemia prior to (2.7 ± 4.5 vs. 4.5 ± 1.4, p = 0.03) and during hospitalization (3.9 ± 1.9 vs. 5.5 ± 1.2, p = 0.04); and had lower mean discharge CBG (159 ± 38 mg/dL vs. 211 ± 67 mg/dL, p = 0.02).ConclusionsInpatient diabetes education has potential to improve treatment satisfaction, and reduce CBG.     

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.     

Altered fibrin-clot properties are associated with retinopathy in type 2 diabetes mellitus

AimThe development and progression of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) have been associated with poor glycaemic control, long disease duration and other clinical features. However, the pathogenesis of the complication is still poorly understood. As the formation of dense fibrin clots resistant to lysis has been described in diabetes patients, this study tested the hypothesis that altered clot structure and function are associated with DR in T2DM patients.MethodsThe study included 101 T2DM subjects without DR (NDR) and 60 with DR. Plasma fibrin-clot permeation was assessed using a pressure-driven system, and expressed as the permeation coefficient (K_s), indicating pore size, and as the time required for a 50% decrease in clot turbidity (t_50%) as a marker of susceptibility to fibrinolysis. All patients underwent ophthalmological examination. Clinical and biochemical co-variables were also measured. Determinants of DR were identified using stepwise, multivariable, logistic-regression analyses.ResultsPatients with DR had lower clot permeability (K_s: 6.15 ± 1.18 vs. 7.53 ± 1.24 10^?9 cm²; P < 0.0001) and slower fibrin-clot lysis (t_50%: 10.12 ± 1.24 vs. 9.12 ± 1.4 min; P < 0.0001) than NDR subjects. Logistic analysis revealed associations between DR and K_s, t_50%, fasting glucose and diabetes duration, as well as insulin treatment and statin non-use (P < 0.05). After adjusting for these variables as well as for age and gender, associations between K_s and t_50% with DR proved to be significant.ConclusionFormation of compact fibrin clots and impaired clot lysis are both associated with DR in T2DM patients. However, it is unclear whether these abnormalities lead to the development of DR or merely constitute a marker of its presence.     

Awareness of risk factors for type 2 diabetes in women with current and former gestational diabetes mellitus (GDM): Implications for future primary diabetes prevention

AimsTo assess the awareness of risk factors for type 2 diabetes and lifestyle changes that can decrease such risks in women with GDM.MethodsThe study comprised responses to health questionnaires by 319 women: 31 pregnant women with current GDM (CGDM), 88 women with previous GDM (PGDM), 100 pregnant women without DM (PWDM) and 100 non-pregnant women without DM (NPWDM). The CGDM group answered the questionnaires at the initiation and 4 weeks after participating in formal education on GDM. Two types of awareness scores (AS) were established. One AS was about the risks associated with GDM (GDMR), and the other was related to the awareness of lifestyle changes that can decrease the risks of type 2 diabetes (DM2R).ResultsThe PGDM group had the highest GDMR and DM2R scores (9.55 ± 2.66) (13.2 ± 2.26) compared with the other groups (CGDM 7.48 ± 3.14, NPWDM 6.10 ± 3.17, PWDM 2.89 ± 2.48) (p < 0.05) and (NPWDM 12.05 ± 2.73, CGDM 11.29 ± 2.45, PWDM 8.27 ± 4.14) (p < 0.05). The CGDM group increased the GDMR score from 7.48 ± 3.14 to 10.54 ± 2.57 (p < 0.0001) and the DM2R score from 11.29 ± 2.45 to 14.04 ± 1.26 (p < 0.001).ConclusionsWomen had limited awareness of risk factors for type 2 diabetes and lifestyle modifications that can decrease such risk of diabetes. AS were higher in women with current and previous GDM after receiving formal education.     

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus

AimsThis study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery.MethodsEighteen type 2 diabetics (age 55 ± 2 years) and twenty healthy controls (age 51 ± 1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade.ResultsThe parasympathetic effect on the RR interval was blunted (P = .004) in diabetic subjects during recovery. Parasympathetic effect on QT–RR slope during early recovery was diminished in the diabetes group (diabetes 0.13 ± 0.02, control 0.21 ± 0.02, P = .03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5 ± 1.9 bpm, control 27.6 ± 1.5 bpm, P < .001).ConclusionsIn subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.     

The feasibility of a self-management education program for patients with type 2 diabetes mellitus: Do the perceptions of patients and educators match?

AimsTo compare the feasibility experienced by patients with type 2 diabetes mellitus in a self-management educational program to the hindrance assessed by the educator of the program.MethodsTwenty-five type 2 diabetes patients on maximally tolerated oral hypoglycaemic agents followed a 6-month educational program consisting of five components: background, medication, physical exercise, nutrition and blood glucose self-monitoring. Medication was unchanged during the study. Outcome measures were feasibility encountered by the patient, hindrance observed by the educator and HbA_1c-level.ResultsThe feasibility encountered by patients was significantly related to the hindrance assessed by the educators (rho 0.756, p < 0.001). Feasibility increased significantly for three components but not for physical exercise and nutritional advice. Mean HbA_1c-level decreased from 8.2 ± 1.1% before onset of the program to 7.2 ± 1.3% 6 weeks after termination of the program.ConclusionsFeasibility experienced by the patients matched the hindrance noticed by the educators. This might have led to an increase in patients’ self-efficacy, which in turn gives an improvement in self-management and glycaemic control.     

Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus

AimsTo compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD.MethodsProspective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention.ResultsMean body-mass-index was 32.7 ± 5.4 kg/m² at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99 ± 4.1 kg, LCD: −4.31 ± 3.6 kg (p < 0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p < 0.009) while no change occurred in the LFD group (p < 0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group.ConclusionsWeight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.     

Impact of flexible insulin therapy on blood glucose variability,oxidative stress and inflammation in type 1 diabetic patients: The VARIAFIT study

AimsHbA_1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.MethodsTests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E₄ (LTE4), 11-dehydro-thromboxane B₂ (TXB2) and 8-iso-prostaglandin F2α (PGF2).ResultsHbA_1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P = 0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥ 0.84, P < 0.0001).ConclusionA FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA_1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).     

Insulin initiation in primary care for patients with type 2 diabetes: 3-Year follow-up study

Purpose of studyTo evaluate the 3-year impact of initiating basal insulin on glycaemic control (HbA1c) and weight gain in patients with poorly controlled type 2 diabetes registered with UK general practices that volunteered to participate in an insulin initiation training programme.MethodsAudit utilising data collected from practice record systems, which included data at baseline, 3, 6 months and subsequent six-monthly intervals post-insulin initiation for up to 10 patients per participating practice.ResultsOf 115 eligible practices, 55 (47.8%) contributed data on a total of 516 patients. The mean improvement in HbA1c levels in the first 6 months was 1.4% (range ?3.8% to 8.2%, median = 1.40%). Thereafter, there was no overall change in HbA1c levels, although the change for individual patients ranged from ?4.90% to +7.50%. At 36 months, 141 (41%) patients for whom data were provided had achieved the pre-2006/2007 UK Quality and Outcomes Framework (QOF) target of 7.4% or less, including 98 (29%) who had achieved an HbA1c of 7% or less. Patients who achieved target had a lower HbA1c at baseline (mean 9.1% compared to 9.7%; p < 0.001); had a lower weight at 36 months (mean 88.0 kg compared to 93.5 kg; p = 0.05); were more likely to be on basal insulin alone (88, 47.1% compared to 46, 34.6%; p < 0.05); and were slightly older (mean 64.5 years compared to 61.7 years; p < 0.05).ConclusionAttending an insulin initiation training programme may successfully prepare primary healthcare professionals to initiate insulin therapy as part of everyday practice for patients with poorly controlled type 2 diabetes. The impact on glycaemic control is maintained over a 3-year period. Although intensification of treatment occurred during this period, the findings suggest scope for further intensification of insulin therapy in order to improve on the glycaemic control achieved during the first 6 months post-insulin initiation.     

No inferioridad de la titulación de enfermera de insuficiencia cardiaca en comparación con la de cardiólogo de insuficiencia cardiaca. Ensayo aleatorizado multicéntrico ETIFIC

Introduction and objectivesBeta-blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin-II-receptor-blockers (ARB), and mineralocorticoid-receptor antagonists decrease mortality and heart failure (HF) hospitalizations in HF patients with reduced left ventricular ejection fraction. The effect is dose-dependent. Careful titration is recommended. However, suboptimal doses are common in clinical practice. This study aimed to compare the safety and efficacy of dose titration of the aforementioned drugs by HF nurses vs HF cardiologists.MethodsETIFIC was a multicenter (n = 20) noninferiority randomized controlled open label trial. A total of 320 hospitalized patients with new-onset HF, reduced ejection fraction and New York Heart Association II-III, without beta-blocker contraindications were randomized 1:1 in blocks of 4 patients each stratified by hospital: 164 to HF nurse titration vs 156 to HF cardiologist titration (144 vs 145 analyzed). The primary endpoint was the beta-blocker mean relative dose (% of target dose) achieved at 4 months. Secondary endpoints included ACE inhibitors, ARB, and mineralocorticoid-receptor antagonists mean relative doses, associated variables, adverse events, and clinical outcomes at 6 months.ResultsThe mean ± standard deviation relative doses achieved by HF nurses vs HF cardiologists were as follows: beta-blockers 71.09% ± 31.49% vs 56.29% ± 31.32%, with a difference of 14.8% (95%CI, 7.5-22.1), P < .001; ACE inhibitors 72.61% ± 29.80% vs 56.13% ± 30.37%, P < .001; ARB 44.48% ± 33.47% vs 43.51% ± 33.69%, P = .93; and mineralocorticoid-receptor antagonists 71% ± 32.12% vs 70.47% ± 29.78%, P = .86; mean ± standard deviation visits were 6.41 ± 2.82 vs 2.81 ± 1.58, P < .001, while the number (%) of adverse events were 34 (23.6) vs 30 (20.7), P = .55; and at 6 months HF hospitalizations were 1 (0.69) vs 9 (5.51), P = .01.ConclusionsETIFIC is the first multicenter randomized trial to demonstrate the noninferiority of HF specialist-nurse titration vs HF cardiologist titration. Moreover, HF nurses achieved higher beta-blocker/ACE inhibitors doses, with more outpatient visits and fewer HF hospitalizations.Trial registry number: NCT02546856.     

Insulin resistance and alanine amino transaminase (ALT) levels in first degree relatives of type 2 diabetes mellitus

IntroductionInsulin resistance is established as an independent predictor of a range of disorders such as obesity, hypertension, dyslipidemia, type 2 diabetes mellitus and atherosclerotic cardiovascular diseases. There is an association of hyperinsulinemia with hypertriglycerdemia, low level of HDL and high level of LDL. In nonalcoholic fatty liver disease, there is an elevation of ALT, raising the possibility that the prospective relationship between ALT and type 2 diabetes may reflect cross-sectional associations with insulin resistance or obesity.Aim and objectiveTo find the significance of insulin resistance and alanine aminotransferase level in first degree relatives of type 2 diabetes mellitus.Materials and methodsThe study included 50 first degree relatives of type 2 diabetes (25 men and 25 women) aged 20–60 years and 30 control of similar age. All cases were taken from SRM Medical College Hospital and Research Centre, Chennai. All the cases were analyzed for HOMA_IR, QUICKI, IR ratio, fasting glucose, insulin (ELISA), lipid profile and alanine aminotransferase. Student's ‘t’ test was applied for statistical analysis.ResultThe data show the significance of insulin resistance (HOMA_IR) (2.76 ± 1.46, 1.35 ± 0.8, p < 0.001) in the first degree relatives of type 2 diabetes mellitus when compared with controls respectively and increased level fasting plasma insulin (12.28 ± 6.16, 6.12 ± 3.04, p < 0.001). In the lipid profile the total cholesterol and TAG are significant. No statistical significance was found in ALT (24.8 ± 9.84, 20.08 ± 11.02).ConclusionResults of the study conclude that there is a high prevalence of insulin resistance in the first degree relatives of type 2 diabetes mellitus. ALT levels in the first degree relatives of type 2 diabetes mellitus had increased levels of insulin resistance, the pathogenesis suggesting increase in ALT levels as seen in insulin resistance condition. In our study, ALT was not statistically significant.     

Vitamin D status,incident diabetes and prospective changes in glucose metabolism in older subjects: The Hoorn study

Background and aimsVitamin D deficiency may contribute to impaired glucose metabolism and type 2 diabetes, especially in the elderly population. We aimed to evaluate whether baseline 25-hydroxyvitamin D (25[OH]D) levels are prospectively associated with deterioration of glucose metabolism and the incidence of diabetes.Methods and resultsWe examined a subsample from the population based Hoorn study among older men and women. Physical examinations were performed from 2000 to 2001 and included measurements of 25(OH)D. Glucose tolerance tests and HbA1c measurements were performed at baseline and at a follow-up between 2007 and 2009. We included 351 study participants (51% females; 67.9 ± 5.7 years). Baseline 25(OH)D levels were 56.7 ± 18.8 nmol/L and follow-up visits were performed after 7.5 ± 0.5 years. Among 280 study participants without diabetes at baseline we recorded 45 cases of incident diabetes. There was no significant association of 25(OH)D with the incidence of diabetes and with fasting and 2 h postload glucose levels at follow-up. In analyses adjusted for age, sex, and baseline HbA1c there was, however, a significant association of 25(OH)D with follow-up HbA1c levels (beta coefficient = ?0.085, p = 0.085). This association was attenuated after further adjustments for BMI (beta coefficient = ?0.079, p = 0.064).ConclusionsIn this study among the older population we observed no significant association of baseline 25(OH)D with glucose metabolism and incident diabetes. We found, however, a non-significant trend towards an inverse association of 25(OH)D with prospective changes in HbA1c that deserves further investigations.     

WHO-5, a tool focusing on psychological needs in patients with diabetes: The French contribution to the DAWN study

AimIn 2001, the international Diabetes Attitudes, Wishes and Needs (DAWN) programme was launched to evaluate the psychosocial impact of diabetes. In France, DAWN experts carried out an observational study to further understand the impact of diabetes on the psychological well-being of people with diabetes, using the French version of the WHO-5 questionnaire.MethodsThe WHO-5, a unidimensional five-item questionnaire that measures positive psychological well-being, was completed by 2213 patients (1670 with diabetes). A total sum score was calculated, ranging on a scale from 0 to 25. A score less than 13 indicated impaired well-being and a score less than 8 reflected likely depression.ResultsThe mean total well-being score for the whole study population was 14.1 ± 5.5, and 14.3 ± 5.5 for patients with diabetes and 13.5 ± 5.4 for patients with other chronic diseases. The average score for patients with diabetes only (15.1 ± 5.2) was higher than those for the other subgroups (P = 0.005), whereas the average scores for those using insulin (14.8 ± 5.2) and women with diabetes (13.2 ± 5.6) were significantly lower compared with the whole diabetic group (15.6 ± 5.1 [P = 0.03] and 15 ± 5.2 [P < 0.001], respectively).ConclusionThe WHO-5 questionnaire showed satisfactory psychometric properties in a large sample of French diabetic patients. The scale is unidimensional and highlighted differences in well-being, which was lower in diabetic women, in patients with other chronic diseases and in those treated with insulin.     

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.     

Clinical profile of patients using normal,high and very high insulin doses in type 2 diabetes

AimsInsulin requirement varies between patients with diabetes due to insulin resistance. The clinical profile of patients based on their insulin requirement has not been studied earlier. We stratified the patients based on total daily insulin requirement (TDIR) and studied their clinical profile and carbohydrate consumption.Materials & methodsSixty patients with type 2 diabetes (aged 30–75 years, using stable insulin dose for last 6 months, HbA1c between 6–7.5 %, negative screening tests for Acromegaly and Cushing's disease) participated in this clinical observational study. All patients with major illness, surgery or diabetic ketoacidosis were excluded. The patients were divided into 3 groups: Group 1 (TDIR <1 U/kg, n = 30), Group 2 (TDIR 1–2 U/kg, n = 20) and Group 3 (TDIR > 2 U/kg, n = 10). Data are presented as mean ± S.D and comparison between three groups was done using one way ANOVA test.ResultsThe patients (27M: 33F) had mean age 54.3 ± 12.3 years, diabetes duration 10.1 ± 4.7 years and an A1c of 7 ± 0.38%. Patients in group 3 had lower body weight, BMI and highest carbohydrate consumption when compared with the other two groups (P < 0.05). Hypoglycemic episodes and complications did not differ between the groups.ConclusionOur data showed that the low body weight and high carbohydrate intake are associated with increased insulin requirement. The clinical implications of our study are to check the carbohydrate intake in patients with high insulin requirement.     

One-year metabolic outcomes in patients with type 2 diabetes treated with exenatide in routine practice

AimThe study objective was to analyze, in everyday practice, the long-term metabolic effects of exenatide (for 9 and 12 months) in patients with type 2 diabetes not responding to treatments with metformin and sulphonylurea at maximum dosages.MethodsA total of 299 type 2 diabetics were recruited from 14 centres specializing in diabetes care across Belgium. Main study endpoints were changes in HbA_1c, weight and waist circumference, and tolerability and compliance. Two patient cohorts were analyzed for effectiveness, with data available at 9 (n = 90) and 12 (n = 94) months of follow-up.ResultsSignificant decreases in HbA_1c of −1.3% and −1.6% were observed in the 9- and 12-month cohorts, respectively (P < 0.001). The decrease in HbA_1c was greater in patients with higher baseline levels (P < 0.001), and the response was independent of baseline weight, body mass index (BMI), age, gender and diabetes duration. A progressive reduction of weight (4.9 kg) was also observed in the two cohorts at 9 and 12 months (P < 0.001), with greater weight loss in patients with higher baseline BMI (P = 0.046) and in female subjects (P = 0.025). Waist circumference also decreased from baseline to endpoints. A correlation was observed between reduction in HbA_1c and weight loss (P = 0.019). Side effects, mainly of gastrointestinal origin, were reported in 33% (93/284 patients in the safety cohort). The rate of hypoglycaemia was 3.5%. Treatment was discontinued in 27% of patients (n = 77) mainly due to drug inefficacy (53%, n = 41) or adverse events (26%, n = 20), or both (8%, n = 6).ConclusionExenatide leads to long-term improvement of glycaemic control as well as weight loss in a majority of patients not responding to combined oral drug therapy in real-world clinical practice. However, no baseline factors predictive of response could be identified. Exenatide can be considered an effective treatment option in such patients, including those with high baseline HbA_1c and long duration of diabetes.     

Diabetic retinopathy in well-controlled type 2 diabetes: Role of glycaemic memory

AimsAs diabetic retinopathy (DR) can occur even in well-controlled patients with type 2 diabetes (T2D), our study sought to determine whether it might be related to ‘glucose memory’ by evaluating patients’ HbA1c over previous years and their skin autofluorescence (SAF).MethodsIn 334 patients with T2D and HbA1c levels ≤ 8%, their available values of HbA1c from previous years were collected, and their SAF measured by an advanced glycation end-product (AGE) reader. Binary logistic regression analysis was then used to correlate DR with previously recorded HbA1c levels and to SAF, with adjustment for DR risk factors [age, gender, BMI, duration of diabetes, arterial hypertension, diabetic kidney disease (DKD), blood lipid levels and statin treatment].ResultsOur patients were mostly men (58.4%) aged 63 ± 10 years, with a duration of diabetes of 13 ± 10 years and HbA1c = 7.1 ± 0.7%. Of these patients, 84 (25.1%) had DR, which was associated with longer duration of diabetes and greater prevalence of DKD. A total of 605 HbA1c values from previous years were collected for time periods ?4 ± 3 months (n = 255), ?16 ± 4 months (n = 152), ?30 ± 4 months (n = 93) and ?62 ± 26 months (n = 105). After adjustment, the association between DR and having an HbA1c higher than the median was significant only for the oldest previous HbA1c values: OR = 6.75, 95% CI: 1.90–23.90. Moreover, SAF values were higher in those with DR [2.95 ± 0.67 arbitrary units (AU)] vs 2.65 ± 0.65 AU with no DR (P < 0.01) and were also associated with the oldest previous HbA1c values (P < 0.01).ConclusionOur study found that 25.1% of our well-controlled T2D patients had DR, which was related to both their HbA1c levels from 5 years prior to study admission and their SAF values, a marker of glucose memory.     

Effect of short-term intensive insulin therapy on the incretin response in early type 2 diabetes

AimsShort-term intensive insulin therapy (IIT) and gastric bypass surgery are both interventions that can improve beta-cell function, reduce insulin resistance and induce remission of type 2 diabetes. Whereas gastric bypass yields an enhanced glucagon-like peptide-1 (GLP-1) response that may contribute to its metabolic benefits, the effect of short-term IIT on the incretin response is unclear. Thus, we sought to evaluate the impact of IIT on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion in early type 2 diabetes.MethodsIn this study, 63 patients (age 59 ± 8.3 years, baseline A1c 6.8 ± 0.7%, diabetes duration 3.0 ± 2.1 years) underwent 4 weeks of IIT (basal insulin detemir and pre-meal insulin aspart). GLP-1, GIP and glucagon responses were assessed by the area-under-the-curve (AUC) of these hormones on oral glucose tolerance tests at baseline and 1-day after the completion of therapy. Beta-cell function was assessed by Insulin Secretion-Sensitivity Index-2 (ISSI-2), with insulin resistance measured by Homeostasis Model Assessment (HOMA-IR).ResultsAs expected, comparing the post-therapy oral glucose tolerance test to that at baseline, IIT increased ISSI-2 (P = 0.02), decreased HOMA-IR (P < 0.001), and reduced AUC_glucagon (P < 0.001). Of note, however, IIT had no significant impact on AUC_GLP-1 (P = 0.24) and reduced AUC_GIP (P = 0.02).ConclusionDespite improving beta-cell function, insulin resistance and glucagonemia, short-term IIT does not change GLP-1 secretion and decreases the GIP response to an oral glucose challenge in early type 2 diabetes. Thus, the beneficial impact of this therapy on glucose homeostasis is not attributable to its effects on incretin secretion.     

Baseline osteocalcin levels and incident diabetes in a 3-year prospective study of high-risk individuals

AimExperimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing β cells. Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose. For this reason, the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospectively tested.MethodsThe study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study (the DE-PLAN study). All participants were free of diabetes at baseline and underwent a second evaluation 3 years later. Diabetes status was defined according to an oral glucose tolerance test.ResultsA total of 307 subjects were included in the present analysis. The population, including 154 men (50.3%), was middle-aged (54.4 ± 10.2 years) and overweight (BMI: 29.5 ± 4.9 kg/m²). At baseline, mean total plasma osteocalcin was lower in those with impaired fasting glucose and/or impaired glucose tolerance compared with those with normal glucose tolerance (6.0 ± 3.1 ng/mL vs. 7.3 ± 4.0 ng/mL, respectively; P = 0.01). After 3 years, 36 subjects had developed diabetes. In the prospective evaluation, there was no association between baseline osteocalcin levels and diabetes (OR: 1.04 per 1 ng/mL, 95% CI: 0.93–1.15; P = 0.49) on multivariable logistic regression analysis, nor was there any correlation with changes in plasma glucose after 3 years (r = 0.09, P = 0.38).ConclusionOur prospective results show that lower levels of circulating osteocalcin do not predict future diabetes development and, in contrast to most cross-sectional published data so far, suggest that this molecule may not be playing a major role in glucose homoeostasis in humans.