Pregnant type 1 diabetes women with rises in C-peptide display higher levels of regulatory T cells: A pilot study.

AIM: During pregnancy of type 1 diabetes (T1D) women, a C peptide rise has been described, which mechanism is unclear. In T1D, a defect of regulatory T cells (Tregs) and its major controlling cytokine, interleukin-2 (IL2), is observed. METHODS: Evolution of clinical, immunological (Treg (CD4+CD25hiCD127-/loFoxp3+ measured by flow cytometry and IL2 measured by luminex xMAP technology) and diabetes parameters (insulin dose per day, HbA1C, glycaemia, C peptide) was evaluated in 13 T1D women during the three trimesters of pregnancy and post-partum (PP, within 6 months) in a monocentric pilot study. Immunological parameters were compared with those of a healthy pregnant cohort (QuTe). RESULTS: An improvement of beta cell function (C peptide rise and/or a decrease of insulin dose-adjusted A1c index that estimate individual exogenous insulin need) was observed in seven women (group 1) whereas the six others (group 2) did not display any positive response to pregnancy. A higher level of Tregs and IL2 was observed in group 1 compared to group 2 during pregnancy and at PP for Tregs level. However, compared to the healthy cohort, T1D women displayed a Treg deficiency CONCLUSION: This pilot study highlights that higher level of Tregs and IL2 seem to allow improvement of endogenous insulin secretion of T1D women during pregnancy.

Evaluation of a 5-day education programme in type 1 diabetes: achieving individual targets with a patient-centred approach.

AIMS: To evaluate if a single inpatient education training programme can achieve individualized therapeutic targets. METHODS: Patients with Type 1 diabetes participating in a flexible intensive therapy programme were consecutively included in a prospective monocentric study. They all participated in the same education programme which had a patient-centred approach. Before the intervention, patients were divided into three groups according to their main therapeutic target: Group 1, to decrease HbA1c concentration in patients with baseline HbA1c ≥ 58 mmol/mol (7.5%); Group 2, to improve quality of life and satisfaction with treatment in patients with baseline HbA1c < 58 mmol/mol (7.5%); and Group 3, to decrease the frequency of hypoglycaemic episodes in patients with severe or frequent hypoglycaemic episodes. Therapeutic targets were evaluated at 12 months. Quality of life and treatment satisfaction were evaluated with validated questionnaires completed at baseline and 6 months. RESULTS: In Group 1 (n = 74), the mean ± sd HbA1c concentration decreased from 75 ± 15 mmol/mol (9.0 ±1.4%) to 68 ±15 mmol/mol (8.4 ± 1.4%; P < 0.001), with 53% of patients experiencing a decrease in HbA1c concentration of at least 6 mmol/mol (0.5%), without weight gain or more frequent hypoglycaemia. In Group 2 (n = 12), patient satisfaction with treatment improved significantly (P < 0.0001). In Group 3 (n = 35), minor hypoglycaemia significantly decreased from a mean ± sd of 6.6 ± 4.7 to 3.2 ± 3.0 hypoglycaemic episodes/week (P < 0.001) and the incidence of severe hypoglycaemia dropped significantly from a mean ± sd of 2.31 ± 3.07 to 0.86 ± 2.46 episodes/patient/year (P < 0.001). CONCLUSIONS: Many patients with different needs, who attended the same flexible intensive therapy education programme, which had a patient-centred approach, were able to achieve their individual therapeutic targets.

A randomized study comparing isotope and echocardiography stress testing in the screening of silent myocardial ischaemia in type 2 diabetic patients.

AIMS: This study aimed to compare the positive predictive value (PPV) of stress myocardial scintigraphy (SPECT) and of dobutamine echocardiography (DE) in the diagnosis of significant coronary artery stenosis (CAD) in asymptomatic type 2 diabetic patients, and to assess long-term clinical outcomes according to silent myocardial ischaemia (SMI) screening. METHODS: A total of 204 asymptomatic type 2 diabetic patients at high cardiovascular (CV) risk were prospectively randomized to undergo either SPECT (n=104) or DE (n=100). Coronary angiography was proposed in cases of SMI, with revascularization of suitable lesions. Intensive treatment of CV risk factors was prescribed for all patients. Death and myocardial infarction (MI) were recorded during the 3-year follow-up. RESULTS: Clinical characteristics were similar in the two testing groups. The prevalence of SMI and significant CAD were 13% and 4%, respectively, in the SPECT group vs 11% and 5%, respectively, in the DE group (not significant [NS]). The PPV for the detection of significant CAD was 29% for SPECT and 45% for DE (NS). Seven patients (3%) underwent initial revascularization. The 3-year rate of CV death and MI was 2.5%, and similar in both groups. CONCLUSION: Rates of SMI and significant CAD in asymptomatic high-risk type 2 diabetic patients receiving intensive care of risk factors are low, and SPECT and DE are similar in the detection of SMI and CAD. Coronary revascularization and intensive CV risk-factor therapy are associated with a low rate of adverse CV events at 3 years, whichever stress test was used.

Insulin therapy for type 2 diabetes: premixed or basal-prandial?

It is logical to begin type 2 insulin therapy with an injection of an intermediate-acting or a long-acting insulin at bedtime, but one should treat to target, i.e. aim at fasting glycaemias lower than 1.20 g/l to obtain an HbA(1c) close to 7%. Nevertheless, basal insulin therapy does not prevent progression to insulin-secretory deficiency. If necessary, recourse should be made to multiple-injection protocols, taking into account postprandial hyperglycaemia. For every level of HbA(1c), the suppression of postprandial hyperglycaemia, 1 point of HbA(1c) can be gained in theory, whereas reducing the fasting glycaemia to values of less than 1.10 g/l reduces HbA(1c) to close to 7%, whatever the initial level of HbA(1c). However, when a diabetic is clearly not controlled, the preprandial acting use of rapid analogues allows the fasting glycaemia to be improved significantly. Inversely, an early treatment with basal insulin, by correcting glucotoxicity, can also decrease postprandial hyperglycaemia. Many industry-sponsored studies comparing insulin therapy regimens show annoying biased interpretations of results. It does not seem pertinent to compare a single injection with two or even three injections, nor to compare an efficient titration with an inefficient titration or to eliminate oral drugs, in particular sulphonylureas combined with a basal insulin. If premix insulins can give satisfactory results in patients who maintain a sufficient residual insulin-secretion, we think it would be preferable to adopt the basal-prandial regimen and a step-by-step escalating therapy. The first stage consists in combining oral therapy with an injection of NPH insulin or a long-acting analogue at bedtime, aiming at a fasting glycaemia of less than 1.20 g/l. In the next stages, a single injection of rapid-acting insulin analogue is added each time. The main advantage of this regimen is to fix a target adapted to each injection and, as a result, to facilitate forced titration of the doses.