J. Bringer

Accuracy of continuous subcutaneous glucose monitoring with the GlucoDay® in type 1 diabetic patients treated by subcutaneous insulin infusion during exercise of low versus high intensity

AIMnThe GlucoDay allows continuous glucose monitoring by subcutaneous microdialysis in sedentary conditions. To validate it when glycaemia may undergo rapid and dramatic changes, we investigated its accuracy during two exercise sessions with markedly different glucose disposal rates.nnnMETHODSnNine male diabetic patients, aged 32-61, treated by insulin pumps, first underwent a standard maximal exercise-test designed for determining the maximal oxygen consumption and the first ventilatory threshold (Vt1). Then two 30 min steady-state workloads at 15% below and 15% above the Vt1 were performed in random order with the GlucoDay, and measurement of CHO oxidation rates was made by indirect calorimetry.nnnRESULTSnCHO oxidation during exercise at +15% Vt1 was higher (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor vs. venous) determinations. The Clarke error grid situates 92.9% of glucose values within the A zone and 6.4% within the B zone, while only one pair of values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly than sensor glucose during exercise. Bland-Altman plots evidence for a few cases of underestimation of venous glucose at high intensity.nnnCONCLUSIONSnThis study showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time in sensor values likely explains a few discrepancies that do not appear as clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy in hypoglycaemia would further support applicability of GlucoDay at exercise.

Abdominal obesity is associated with ineffective control of cardiovascular risk factors in primary care in France.

AIMnInsufficient control of cardiovascular risk factors is observed in primary care. The goal of the present study was to evaluate the association of abdominal obesity with achievement of treatment targets for HbA(1c), LDL cholesterol, triglycerides, HDL cholesterol and blood pressure in primary care.nnnMETHODSnIn this cross-sectional observational epidemiological study, primary-care practitioners completed a questionnaire covering demographic and socioeconomic data, medical history, drug treatment, and clinical and biological characteristics for 3351 patients (1630 men and 1721 women). Therapeutic targets were HbA(1c) <7%, LDL cholesterol <1.6g/L, triglycerides <1.5 g/L and SBP/DBP <140/90 mmHg. Multivariate analyses were performed to assess the relationship between waist circumference and a lack of cardiovascular risk-factor control.nnnRESULTSnThe patients mean ages were 58+/-14 years and 55+/-16 years for men and women, respectively. A large waist circumference was positively and significantly (P<0.0001 for all) associated with diabetes, hypercholesterolaemia, hypertriglyceridaemia, low HDL cholesterol and hypertension. The prevalence of patients not achieving therapeutic targets increased across waist-circumference quartiles. For treated patients, the odds ratios (95% CI) (adjusted for age, gender, education, smoking status and medical specialty) for not achieving treatment targets were 17.6 (2.2-142) for triglycerides, 2.8 (1.3-6.1) for HbA(1c) and 1.4 (0.9-2.0) for blood pressure on comparisons with extreme quartiles of waist-circumference distribution.nnnCONCLUSIONnIn primary care, a lack of control of triglycerides, HbA(1c) and, to a lesser extent, blood pressure increases with waist circumference independently of confounders. This suggests that abdominal obesity is associated of poor results in the treatment of diabetes and hypertriglyceridaemia.

Continuous glucose monitoring reduces both hypoglycaemia and HbA1c in hypoglycaemia-prone type 1 diabetic patients treated with a portable pump.

AIMnThis study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes.nnnMETHODSnThirteen patients with type 1 diabetes (diabetes duration: 25±15 years; CSII duration: 5.5±7.0 years), with more than six recorded capillary blood glucose (CBG) values <60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT(®), Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60 mg/dL and HbA(1c) levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups.nnnRESULTSnFour patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9±9.2 to 7.6±6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA(1c) from 8.3±0.7 to 7.7±0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected.nnnCONCLUSIONnThis pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII.

Prise de position de la Société Francophone du Diabète (SFD) sur la prise en charge médicamenteuse de l'hyperglycémie du patient diabétique de type 2

Composition du groupe de relecture Mme Carole Avril, Directrice Générale de la Fédération Française des Diabétiques (Paris) Dr Éric Drahi, médecin généraliste (Saint-Jean-de-Braye) Pr Jean Doucet, interniste gériatre et diabétologue, Professeur de Thérapeutique (Rouen) Pr Serge Halimi, endocrinologue-diabétologue, Professeur Émérite de Nutrition (Grenoble) Pr Anne-Marie Magnier, Professeur Honoraire de Médecine Générale (Paris, Sorbonne) Dr Laurent Meyer, endocrinologue-diabétologue (Strasbourg) Pr Ronan Roussel, endocrinologue-diabétologue (Paris, Diderot) Dr Pierre Serusclat, endocrinologue-diabétologue (Vénissieux) Pr Charles Thivolet, endocrinologue-diabétologue (Lyon) Composition du groupe de travail de la SFD Pr Bernard Bauduceau (endocrinologuediabétologue, Saint-Mandé), Pr Lyse Bordier (endocrinologue-diabétologue, Saint-Mandé), Pr Bernard Charbonnel (endocrinologue-diabétologue, Nantes), Pr Emmanuel Cosson (endocrinologuediabétologue, Bobigny), Pr Patrice Darmon (endocrinologue-diabétologue, Marseille), Dr Bruno Detournay (CEMKA-EVAL, Bourg-la-Reine), Pr Pierre Fontaine (endocrinologue-diabétologue, Lille), Pr André Grimaldi (endocrinologue-diabétologue, Paris), Pr Pierre Gourdy (endocrinologue-diabétologue, Toulouse), Pr Bruno Guerci (endocrinologue-diabétologue, Nancy), Pr Hélène Hanaire (endocrinologue-diabétologue, Toulouse ; présidente de la SFD), Pr Alfred Penfornis (endocrinologue-diabétologue, Corbeil-Essonnes), Pr André Scheen (endocrinologue-diabétologue, Liège, Belgique).

Accuracy assessment of online glucose monitoring by a subcutaneous enzymatic glucose sensor during exercise in patients with type 1 diabetes treated by continuous subcutaneous insulin infusion.

AIMnOnline continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous needle-type enzymatic sensor.nnnMETHODSnTen patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous needle-type enzymatic glucose sensor linked to a portable monitor (Guardian(®) RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T(-10) to T(+30), then every 10 min during the recovery period from T(+30) to T(+90). These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples.nnnRESULTSnSensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: -3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: -15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland-Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively.nnnCONCLUSIONnBlood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM.

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

OBJECTIVESnNew 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.nnnPATIENTS AND METHODSnOver 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 HbA1c were assessed at 3, 6 and 12 months and at the last visit to our centre.nnnRESULTSnImmediately 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>12h/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).nnnCONCLUSIONnHyperglycaemia 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.

Use of Vildagliptin in Management of Type 2 Diabetes: Effectiveness, Treatment Persistence and Safety from the 2-Year Real-Life VILDA Study.

IntroductionThere is an increasing interest for real-life data on drug use in many countries. Reimbursement authorities more and more request observational studies to assess the conditions of use of the products but also to improve knowledge about efficacy and safety in the real world and on a longer term than in clinical trials.AimTo evaluate the effectiveness, treatment persistence and tolerability of vildagliptin in clinical practice.MethodsThis observational, 2-year prospective cohort study was conducted in France on request of the Health Authorities [Haute Autorite de Sante (HAS)]. Type 2 diabetic mellitus (T2DM) patients initiating vildagliptin (including the fixed combination vildagliptin-metformin) or treated for <6xa0months were recruited through a national representative sample of general practitioners (GPs) (nxa0=xa0482) and diabetologists (nxa0=xa084) between March 2010 and December 2011. At inclusion and each follow-up visit atxa0~xa06, 12, 18 and 24xa0months, a questionnaire was completed by the physician collecting information on socio-demographic, clinical and biological data, treatments and adverse events.Results1,700 patients were included: 60% were males, aged 63xa0±xa011xa0years, with diabetes duration 7xa0±xa06xa0years and body mass index (BMI) 30xa0±xa06xa0kg/m2. 45% were obese, 70% treated for hypertension and 66% for dyslipidemia. 64% of the patients received vildagliptin in dual therapy with metformin. 82% of patients completed the 2-year follow-up. Glycosylated hemoglobin (HbA1c) decreased from a mean baseline of 7.8xa0±xa01.2% when vildagliptin was started, to 7.0xa0±xa01.1% at 6xa0months and remained stable thereafter over 2xa0years. Mean weight, glomerular filtration rate, liver enzymes, and lipid parameters were unchanged over the study period. Eight patients (0.5%), all concomitantly treated with insulin and/or sulphonylureas, reported one severe hypoglycemia and 47 (2.9%) patients reported 64 non-severe symptomatic hypoglycemia (59% occurred when patients were treated with insulin and/or sulphonylureas). At 6xa0months, 44.9% of vildagliptin-treated patients reached an HbA1c <7% without hypoglycemia and no weight gain, and this percentage increased to 49.7% at 24xa0months. Vildagliptin treatment maintenance at 2xa0years was 88.8% [95% CI (87.2%; 90.4%)], with 4% of patients discontinuing for adverse events.ConclusionsIn everyday conditions of care, vildagliptin efficacy was in line with existing data from randomized clinical trials, sustained over 2xa0years, with low discontinuation rate and low hypoglycemia risk.

Towards an artificial pancreas at home

AIMnTo review the recent clinical research related to the development of an artificial pancreas and the current perspectives for its home use.nnnMETHODSnAll clinical investigations assessing closed-loop insulin delivery systems in diabetic patients in the literature were collected and analyzed to identify any significant advances as well as bottlenecks.nnnRESULTSnThe development of an artificial pancreas for ambulatory use offering an optimal substitute for insulin secretion has shown promising evolution over the past decade. The accumulated improvements achieved on the performance of insulin pumps using subcutaneous and intraperitoneal routes, continuous glucose monitoring and algorithms driving insulin infusion according to glucose measurement have led to numerous clinical trials recently, albeit only in a hospital setting so far. The key obstacles to achieving permanent normal glucose control are related to the delay of insulin action when infused subcutaneously or, at a lesser extent, into the peritoneal cavity, and blood glucose estimation made by subcutaneous interstitial measurement. These time lags impair the reactivity of the system, and suggest a need to develop complex algorithms aiming at their compensation. So far, manual interventions are needed at times of food intake to prevent hyper- or hypoglycaemic excursions when insulin changes rapidly.nnnCONCLUSIONnThe most recent models using subcutaneous insulin infusion and glucose measurements linked by predictive control algorithms offer sufficient effectiveness and safety to consider their forthcoming use at home, during the night as a first step.

Attempt to improve glucose control in type 2 diabetic patients by education about real-time glucose monitoring

The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system (Guardian RT) to improve glucose control was investigated in patients with poorly controlled type 2 diabetes despite insulin therapy. Ten patients participated in a randomized crossover study comparing two 3-month periods, during which glucose levels were monitored by either self-monitoring of blood glucose (SMBG) alone or by Guardian RT (restricted to 1 week per month) in addition to SMBG. Only four of the enrolled patients completed both periods, while dropouts were mainly due to technical difficulties in using the device. All six patients who completed the first 3-month period showed a reduction in glycated haemoglobin (HbA(1c)) level whatever the mode of glucose monitoring (study effect). A further reduction in HbA(1c) level was observed in two of the three patients using the Guardian RT during the second period. Less frequent symptomatic hypoglycaemic episodes were noted during the 3-month period with the device in the four patients who completed both study periods. These limited, but promising, results of this pilot study appear to justify the initiation of a larger study to assess the use of a real-time glucose sensor in carefully selected patients with type 2 diabetes.

Education on sensor-augmented pump use improves glucose control in type 1 diabetic patients

A rather large subset of type 1 diabetic patients fails to achieve their therapeutic goals in spite of a basal-bolus insulin regimen, frequent self-monitoring of capillary blood glucose (CBG) and tight medical follow-up [1]. Therefore, we investigated prospectively the effectiveness of specific education on the use of a sensor-augmented pump for improving glucose control in such poorly controlled type-1 diabetes patients in clinical practice. Nine patients (six men, three women), aged 49 ± 13 (mean ± SD) years, with type 1 diabetes since age 30 ± 11 years and a sustained glycated haemoglobin (HbA