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.     

Are elderly patients with diabetes being overtreated in French long-term-care homes?

AimIn France, diabetes prevalence and ageing of the population are both on the increase, yet little information on diabetes in elderly patients living in geriatric institutions is available. Moreover, institutionalized diabetic patients are not included in the French recommendations for the management of diabetes in the elderly. For this reason, the aim of the present study was to evaluate diabetes management in older, institutionalized patients.MethodsThe medical records of 100 diabetic patients, aged 65 years and over, and living in seven geriatric institutions in the Côte d’Or region of France, were studied from May 2008 to January 2009.ResultsPrevalence of diabetes in these seven geriatric institutions was 15.46 ± 4.9%, higher than in the general population. The diabetic patients had a mean age of 81.85 ± 11.93 years, and 32% had glycated haemoglobin (HbA_1c) less or equal to 6.5%, indicating a high risk of severe hypoglycaemia. A diet for diabetes was prescribed in 54% of the patients, but HbA_1c levels did not differ between patients following and not following the diet (7.26 ± 1.36% vs 7.11 ± 1.10%, respectively; P = 0.27). Creatinine was assessed in 87% of the patients, and 16% were ophthalmologically followed-up. Daily capillary blood glucose monitoring was performed in 100% of the patients taking insulin and in 17% of those taking oral antidiabetic treatment (P < 0.0001).ConclusionOur data show that, among older institutionalized patients, the prevalence of diabetes is high and the control of diabetes too tight, with a potential risk of hypoglycaemia. Antidiabetic treatment should be reduced when the HbA_1c value is less than 7.5% in this frail and functionally dependent population. Furthermore, a diabetic diet, prescribed for more than half this population, is useless for glycaemic control and may even impinge on quality of life.     

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.     

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%.     

The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients

Background and aimsCardiovascular diseases are the major cause of mortality among diabetic patients. The concentration of malondialdehyde (MDA) and homocysteine is believed to play a role in cardiovascular diseases. Omega-3 fatty acid supplementation could be effective in some diabetes complications and in the control of the glycemic index. However, it may increase lipid peroxidation. The objective of this study was to determine the effect of omega-3 fatty acids on the concentration of homocysteine and MDA in diabetic patients.Methods and resultsA randomized double-blind, placebo-controlled clinical trial was conducted on 81 patients with type 2 diabetes. The patients were randomly assigned to either the treatment or control groups. Each subject received three capsules of omega-3 fatty acids or a placebo every day for a period of 2 months. The two groups were similar in terms of body mass index and food intake. At the beginning of the study and after 2 months of supplementation their levels of HbA₁c, homocysteine, MDA, C-reactive protein (CRP), total cholesterol, LDL-cholesterol and fasting blood sugar (FBS) were determined. Due to omega-3 fatty acid supplementation, homocysteine was changed significantly in both treatment and control groups up to ?3.10 μmol/L and 0.10 μmol/L respectively, and HbA₁c decreased by 0.75% in the treatment group and increased by 0.26% in the control group. However, the changes in fasting blood sugar (FBS), malondialdehyde (MDA), C-reactive protein (CRP), total cholesterol and LDL-cholesterol levels were not significant.ConclusionThe consumption of omega-3 fatty acid supplements (3 g/day) for 2 months decreases the levels of homocysteine in diabetic patients with no change in FBS, MDA and CRP levels.     

Efficacy of benfluorex in combination with sulfonylurea in type 2 diabetic patients: An 18 to 34-week,open-label,extension period

AimThe aim of this trial was to obtain further data on the efficacy and safety of benfluorex as an add-on therapy in type 2 diabetic patients insufficiently controlled by sulfonylurea monotherapy who had a limitation for the use of metformin during a 4-month extension period following a 4-month double-blind trial.MethodsPatients who completed the 18-week double-blind period entered the 16-week extension period. Patients in the benfluorex group during the double-blind period continued benfluorex 450 mg/day (B-B group), whilst patients in the placebo group switched to benfluorex 450 mg/day (P-B group). The main efficacy criterion was HbA_1c, analyzed as the change from week 18 (W18) to the end of treatment using a two-sided Student paired t-test. Secondary criteria were fasting plasma glucose (FPG), insulin resistance and lipids.ResultsBetween W18 and the end of treatment, HbA_1c decreased in the P-B group from 8.53 ± 1.37% to 7.49 ± 1.04% (P < 0.001) and remained stable in the B-B group from 7.52 ± 1.07% to 7.53 ± 1.14% (NS). In the P-B group, parameters of glycemic control showed improvements from W18 to week 34 (W34) which were similar to those observed from baseline to W18 in the B-B group. Overall, the target HbA_1c (≤ 7%) was achieved in 36% (103 of 289) of patients and a decrease in HbA_1c of at least 1% was seen in 44% (128 of 289) of patients. Digestive disorders were the most common adverse events and the incidence of diarrhoea was 4.9% in patients receiving benfluorex for 34 weeks.ConclusionThe beneficial effect of benfluorex as add-on therapy in lowering HbA_1c at W18 was maintained at W34 without evidence for a loss of efficacy or an increased incidence of side effects over a 34-week follow-up.     

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.     

Xanthine oxidase and lens oxidative stress markers in diabetic and senile cataract patients

Xanthine oxidase (XOD) is a prooxidant enzyme possibly implicated in diabetic lens injury and genesis of senile cataract (SC). We evaluated the impact of diabetes on XOD activity and its relationships with lens oxidative stress markers in patients operated on for SC. Serum and lens XOD activities, lens malondialdehyde (MDA), conjugated dienes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) levels were measured in 62 non-diabetic and 29 diabetic patients operated on for SC. Lens XOD, SOD, GPx and GSH levels were gradually declining, while MDA and serum XOD were increasing with patient's age. Lens XOD activity was positively correlated with conjugated dienes concentration (rho = 0.316; p = 0.003) while being inversely correlated with age (rho = ? 0.371; p < 0.001), indicating that low ocular expression of XOD could be related to lower intensity of oxidative stress and delayed occurrence of SC. When samples were adjusted for confounding factors, serum XOD (p < 0.001), lens XOD (p = 0.003) and conjugated dienes (p = 0.002) were significantly higher in diabetic than in non-diabetic group. Lens SOD and GPx were moderately increased while MDA and GSH were unchanged in diabetic, compared with non-diabetic SC group. Blood HbA_1C concentration was positively correlated with lens XOD (rho = 0.346; p < 0.001) as well as serum XOD activity (rho = 0.485; p < 0.001). These results suggest that poor glycemic control may upregulate systemic and ocular XOD activities contributing to lens oxidative stress and possibly to earlier onset of cataract.     

Insulin detemir improves glycaemic control with less hypoglycaemia and no weight gain: 52-week data from the PREDICTIVE? study in a cohort of French patients with type 1 or type 2 diabetes

AimPREDICTIVE™ (an ongoing multinational observational study) provides an opportunity to explore the impact of insulin detemir use in routine clinical practice. Here, we report on long-term (52-week) data from a French cohort of patients (n = 1772), comprising 643 with type 1 diabetes and 1129 with type 2 diabetes.MethodsPatients were prescribed insulin detemir at their physician's discretion and assessed at various visits (baseline, 12 weeks, 26 weeks and 52 weeks). The primary endpoint was the frequency of serious adverse drug reactions, including major hypoglycaemia. Secondary endpoints included minor and nocturnal hypoglycaemia, glycaemic control (HbA_1c, fasting blood glucose and variability of fasting blood glucose) and weight change.ResultsThe incidence of serious adverse drug reactions was low throughout the study, seen in 10 patients with type 1 diabetes (14 events, 1.6%) and seven with type 2 diabetes (seven events, 0.6%). In both type 1 and type 2 diabetes cohorts, the overall minor and nocturnal hypoglycaemic events were reduced from baseline (P < 0.001), with no clinically significant changes in weight from baseline to endpoint. After 52 weeks of treatment with insulin detemir, glycaemic control improved, with reductions in: HbA_1c, by −0.6% and −0.8% in type 1 and type 2 diabetes patients, respectively; fasting blood glucose, by −1.4 mmol/L and −1.9 mmol/L respectively; and FBG variability, by −0.8 mmol/L and −0.3 mmol/L, respectively (P < 0.0001 for all).ConclusionPatients treated with insulin detemir in a clinical healthcare setting improved their glycaemic control with no increases in hypoglycaemia, adverse events or weight compared with baseline.     

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.     

The prevalence of Hypogonadism among diabetic and non-diabetic men in Jordan

ObjectiveDetermine the prevalence of hypogonadism among diabetic and non-diabetic men in Jordan.Research Design and MethodsA cross-sectional study of 1717 men (1089 participants with type 2 diabetes and 628 non-diabetic subjects). Both groups were inquired to answer the Androgen Deficiency for aging male (ADAM) questionnaire. Early morning Total testosterone, prolactin, sex hormone binding globulin, follicle stimulating hormone, leutinizing hormone, HbA1c and fasting blood sugar were measured. Hypogonadism was defined as total testosterone < 3 ng/ml and calculated free testosterone < 5 ng/dl.ResultsThe prevalence of Hypogonadism among all study participants was 18.5%. The prevalence of Hypogonadism in diabetic and non-diabetic men was 24.3% and 8.3%, respectively. The mean (SD) total testosterone concentration of diabetic and non-diabetic men was 3.78 ng/ml (1.7) and 4.92 ng/ml (2.5), respectively (P- value < 0.005).In response to (ADAM) questionnaire, 19.8% of diabetics and 3% of the non-diabetics had symptomatic androgen deficiency (P value < 0.005). Hypogonadism and symptomatic androgen deficiency were negatively and significantly related to diabetes, monthly income and age (P value < 0.005).ConclusionHypogonadism is a prevalent disorder among Jordanian diabetic population. Symptoms of androgen deficiency should be corroborated with testosterone level to establish a multidisciplinary approach for management of hypogonadism.     

Continuous glucose monitoring after kidney transplantation in non-diabetic patients: Early hyperglycaemia is frequent and may herald post-transplantation diabetes mellitus and graft failure

ObjectivesNew onset of diabetes after transplantation (NODAT) is a known complication of renal transplantation, but early glycaemic status after transplantation has not been described prospectively. This study aimed to assess blood glucose (BG) levels immediately following kidney transplantation in non-diabetic subjects and to explore their relationship to later graft outcomes and NODAT occurrence.Patients and methodsOver a 9-month period, 43 consecutive non-diabetic patients who received a kidney transplant were prospectively investigated. During the first 4 days after transplantation, fasting BG was measured and the 24-h BG profile assessed by continuous glucose monitoring (CGM). Capillary BG was measured on hospital admittance and at least four times a day for CGM calibration thereafter. All adverse events were recorded, and fasting BG and HbA_1c were assessed at 3, 6 and 12 months and at the last visit to our centre.ResultsImmediately following renal transplantation, capillary BG was 12.2 ± 3.8 mmol/L. On day 1 (D1), fasting BG was 9.9 ± 4.3 mmol/L and decreased to 6.0 ± 1.5 mmol/L on D3. The CGM-reported mean 24-h BG (mmol/L) was 10.2 ± 2.4 on D1, 7.7 ± 1.3 on D2 and 7.5 ± 1.1 on D3. From D1 to D4, 43% of patients spent > 12 h/day with BG levels > 7.7 mmol/L. While morbidity during the 3 months following transplantation appeared unrelated to BG, the first post-transplantation capillary BG measurement and fasting BG on D1 tended to be higher in patients who developed diabetes 3 months later. Tacrolimus treatment was associated with a higher incidence of dysglycaemia at 3 and 6 months. After a mean follow-up of 72 months, NODAT was frequently seen (18.6%), and was associated with tacrolimus medication (P < 0.01) and a higher rate of renal transplantation failure (RR: 3.6, P < 0.02).ConclusionHyperglycaemia appears to be a nearly constant characteristic immediately following transplantation in non-diabetic kidney recipients. Higher BG values could identify patients at risk for later post-transplant diabetes and graft failure.     

Characteristics and management of diabetic patients hospitalized for myocardial infarction in France

AimThe objective of this study was to compare the management of diabetic and non-diabetic patients before, during and after hospitalization for myocardial infarction (MI).MethodsHospital admissions for MI in France from January to June 2006 were obtained from the national hospital-discharge database and merged with data on medications, 6 months before and after hospitalization of patients covered by the general health insurance scheme. Diabetic patients were identified by having at least two refunds for antidiabetic medications 6 months before the index hospitalization. Results comparing diabetic and non-diabetic patients were adjusted for age and gender.ResultsOf the 14,007 patients included in the study, 2545 were diabetic (18.2%). Before hospital admission, diabetic patients more frequently received secondary cardiovascular preventative medications (12.7% vs 4.2%; P < 0.0001) and stent implants (4.2% vs 2.2%; P < 0.0001) than did non-diabetic patients. During hospitalization and the following month, angioplasty (56.1% vs 61.7%; P = 0.0001) and stent implantation (53.3% vs 59.3%; P < 0.0001) were less frequently performed in diabetic patients and only coronary angiography was done in similar proportions of diabetic and non-diabetic patients (16.7% vs 15.2%). In addition, during the 6 months after hospitalization, diabetic vs non-diabetic patients had more admissions for cardiovascular reasons (36.9% vs 29.5%; P < 0.0001) and were prescribed more secondary preventative medications (65.9% vs 61.7%; P < 0.0001). They were also more frequently treated with insulin only (19.6% 6 months before vs 27.2% 6 months after) or oral antidiabetic drugs (14.6% vs 19.7%, respectively) than were non-diabetics.ConclusionFrench diabetic patients subsequent to MI undergo fewer angioplasty procedures than do non-diabetic patients. After the acute stage, secondary preventative medications are used more often, with a marked rise in the use of insulin.     

Skin autofluorescence is associated with past glycaemic control and complications in type 1 diabetes mellitus

As skin autofluorescence (AF) can assess subcutaneous accumulation of fluorescent advanced glycation end-products (AGEs), this study aimed to investigate whether it was linked to glycaemic control and complications in patients with type 1 diabetes mellitus (T1DM). Using the AGE Reader™, AF was measured in T1DM patients referred to Haut-Levêque Hospital (Bordeaux, France); data on their HbA_1c levels measured every 6 months as far back as the last 5 years were also collected. The association of AF with the patients’ past glucose control, based on their latest HbA_1c values, and the means of the last five and 10 HbA_1c values, and with diabetic complications was also examined by linear regression analysis. The sample included 300 patients: 58% were male; the mean age was 49 (SD 17) years and the mean diabetes duration was 21 (SD 13) years. The median skin AF measurement was 2.0 [25th–75th percentiles: 1.7–2.4] arbitrary units (AU), and this was associated with age (β = 0.15 per 10 years, P < 0.001) and diabetes duration (β = 0.17 per 10 years, P < 0.001). After adjusting for age and estimated glomerular filtration rate (eGFR), the skin AF measurement was also related to the means of the last five and 10 HbA_1c values (β = 0.10 per 1% of HbA_1c, P = 0.005, and β = 0.13 per 1% of HbA_1c, P = 0.001, respectively). In addition, the skin AF was associated with retinopathy (P < 0.001), albuminuria (P < 0.001) and decreased eGFR (P < 0.001). In conclusion, the skin AF is related to the long-term glucose control and diabetic complications.     

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.     

Prognostic value of hyperglycemia on-admission in diabetic versus non-diabetic patients presenting with ST-elevation myocardial infarction in Tunisia

BackgroundHyperglycemia on-admission is a powerful predictor of adverse events in patients presenting for ST-elevation myocardial infarction (STEMI).AimIn this study, we sought to determine the prognostic value of hyperglycemia on-admission in Tunisian patients presenting with STEMI according to their diabetic status.MethodsPatients presenting to our center between January 1998 and September 2014 were enrolled. Hyperglycemia was defined as a glucose level ≥11 mmol/L. In-hospital prognosis was studied in diabetic and non-diabetic patients. The predictive value for mortality of glycemia level on-admission was assessed by mean of the area under receiver operating characteristic (ROC) curve calculation.ResultsA total of 1289 patients were included. Mean age was 60.39 ± 12.8 years and 977 (77.3%) patients were male. Prevalence of diabetes mellitus was 70.2% and 15.2% in patients presenting with and without hyperglycemia, respectively (p < 0.001). In univariate analysis, hyperglycemia was associated to in-hospital death in diabetic (OR: 8.85, 95% CI: 2.11–37.12, p < 0.001) and non-diabetic patients (OR: 2.57, 95% CI: 1.39–4.74, p = 0.002). In multivariate analysis, hyperglycemia was independently predictive of in-hospital death in diabetic patients (OR: 9.6, 95% CI: 2.18–42.22, p = 0.003) but not in non-diabetic patients (OR: 1.93, 95% CI: 0.97–3.86, p = 0.06). Area under ROC curve of glycemia as a predictor of in-hospital death was 0.792 in diabetic and 0.676 in non-diabetic patients.ConclusionIn patients presenting with STEMI, hyperglycemia was associated to hospital death in diabetic and non-diabetic patients in univariate analysis. In multivariate analysis, hyperglycemia was independently associated to in-hospital death in diabetic but not in non-diabetic patients.     

Real-life comparison of DPP4-inhibitors with conventional oral antidiabetics as add-on therapy to metformin in elderly patients with type 2 diabetes: The HYPOCRAS study

AimDespite half of all type 2 diabetes mellitus (T2DM) patients being over 65 and treatment being complicated by an elevated risk of iatrogenic hypoglycaemia, information about antidiabetic treatment is scarce in this age group. This prospective observational study compares DPP4-inhibitors (DPP4-i) with conventional oral antidiabetic drugs (COAD) in the real-life treatment of elderly patients with T2DM uncontrolled on metformin alone.MethodsTwo treatment cohorts (DPP4-i and COAD, constituted on the basis of the GP decision of add-on therapy at the 1st visit) were compared after 6 months. The primary objective was to assess the incidence of hypoglycaemic episodes in relationship with glycaemic control assessed by HbA_1c level.ResultsDemographics and disease history were comparable between the two cohorts (DPP4-i, n = 931 and COAD, n = 257) at baseline. The incidence of hypoglycaemia/severe hypoglycaemia was significantly higher over 6 months in the COAD cohort (20.1%/2.4% vs. 6.4%/0.1%; P < 0.001) whereas similar improvements were observed in glycaemic control with HbA_1c down from 7.9% to 7.0% (COAD) and 6.9% (DPP4-i). The 7% target was reached without hypoglycaemia in more patients in the DPP4-i than in COAD cohort (59.7% vs. 45.5%; P < 0.001). Patients in both cohorts who experienced hypoglycaemia more frequently had a pre-existing diabetic complication. The COAD was more likely to be discontinued (6.6% vs. 1.6%; P < 0.001).ConclusionThis large cohort study of elderly T2DM patients in France shows that the incidence of hypoglycaemia was three times higher in patients prescribed a COAD versus a DPP4-i after 6 months while both treatments induced satisfactory glycaemic control.     

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.     

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.