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

AIMS: HbA1c 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. METHODS: Tests 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). RESULTS: HbA1c (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). CONCLUSION: A FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA1c, 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).

Basal insulin dose in 40 type 1 diabetic patients remains stable 1 year after educational training in flexible insulin therapy.

AIM: Basal insulin dose (BID) determination is the key to successful flexible insulin therapy (FIT). As our hypothesis was that BID changes over time, the primary objective of the present study was to determine the changes in BID 1 year after a therapeutic educational programme on FIT. METHODS: This single-centre retrospective study recruited the first 40 type 1 adult diabetic patients undergoing an educational FIT programme, which was conducted over a 4-day hospital stay and included a carbohydrate-fasting test. RESULTS: Patients' BIDs decreased between Day 0 and Day 4 after the programme (0.31±0.11IU/kg/day vs 0.27±0.09IU/kg/day; P<0.0001), and was increased at 1 year (0.29±0.09IU/kg/day; P=0.004). There was no significant variation in prandial insulin requirements. A tendency toward a reduction in HbA(1c) was observed at 1 year (8.3±1.4% vs 8.1±1.6%; P=0.075), with a decrease by more than 0.5% in 37.5% of patients. Body weight increased at 1 year (66.9±10.4 kg vs 68.1±10.7 kg; P=0.003), and the gain was greater than 5% in 7.5% of patients. Frequency of mild hypoglycaemia either remained stable (40%) or decreased (30%). Only nine patients (baseline HbA(1c) 8.03±1.7%, baseline BID 0.27±0.09IU/kg/day) had BID increases more than 20%, with no changes in prandial insulin requirements and no distinctive phenotype. Baseline HbA(1c), and BID have an impact on the BID at 1 year of approximately 0.3IU/kg/day in most patients. CONCLUSION: The stability of BID over 1 year, with values close to 0.3IU/kg/day associated with a trend towards improvement in HbA(1c), reduction in the frequency of mild hypoglycaemic episodes and absence of major weight gain, supports the relevance of FIT educational training.

Quality of life after islet transplantation: data from the GRAGIL 1 and 2 trials.

BACKGROUND: Rigorous assessment of health-related quality of life (HRQL) is mandatory to establish the benefits of islet transplantation. METHODS: The 36-Item Short Form Health Survey (SF-36) and the Diabetes Quality of Life (DQOL) scales were completed by patients included in an Islet Transplantation Alone (ITA) trial (n = 10) and an Islet After Kidney (IAK) trial (n = 10). RESULTS: The two populations differed by HRQL scores at baseline, with poorer scores in ITA patients. SF-36 scores for physical limitations, bodily pain, general health perception, social functioning, and health transition improved significantly in ITA patients 6 and 12 months post transplantation. The DQOL global score was significantly improved at 6 months and remained so at 12 months, because of a significant improvement in the dimensions of satisfaction and impact of diabetes. No improvement was observed in the IAK patients. CONCLUSION: HRQL assessment may help in the selection of candidates with brittle diabetes for islet transplantation.

A prospective study of quality of life in 77 type 1 diabetic patients 12 months after a hospital therapeutic educational programme.

AIM: The aim of therapeutic education includes improvement of quality of life (QOL). However, the majority of studies are focused on biomedical or behavioural markers only. We performed a prospective study to assess QOL in adult type 1 diabetic patients for one year following a hospital educational programme. METHODS: During this prospective single-centre study, QOL was assessed by the DQOL questionnaire in 77 consecutive patients at baseline and three, six and 12 months after a three-day educational programme. RESULTS: The rate of response was 72.7% (n=55) at three months and 67.5% (n=52) at one year. The overall DQOL score improved at three months from 65.6+/-10.1 to 70.1+/-10.4 (P<0.001), and at one year from 65.1+/-10.4 to 68.5+/-11.7 (P=0.001). Patients exhibited greater satisfaction (66.3+/-15 versus 75.3+/-14.1, P<0.001), a diminished impact of diabetes (61.2+/-10 versus 63.4+/-9.6, P=0.016) as well as of anxiety related to diabetes (67.6+/-18.6 versus 73.6+/-16.2, P=0.009) at three months. This significant improvement was maintained at one year. Improvement in DQOL score at three months was positively correlated with a reduction in HbA(1c) (7.6+/-1.4% versus 7.8+/-1.4%, P=0.032), (r=-0.293, P<0.037). Patients with serious hypoglycaemia before the programme appeared to derive greater benefit from therapeutic education (OR: 9.88, 95% CI: 1.094-89.20). CONCLUSION: QOL assessed by DQOL improved after therapeutic education and during the following year. The improvement in DQOL score at three months correlated with a reduction in HbA(1c) levels and appeared to particularly benefit to those who had severe hypoglycaemia before the programme.

[New therapies for type 2 diabetes: what place for incretin-based agents and rimonabant compared to the previous ones?]. / Les nouveaux traitements du diabète de type 2: quelle place pour les incrétines et le rimonabant par rapport aux précédents?

Treatment of type 2 diabetes (T2DM) is based on lifestyle changes and oral antidiabetic agents or insulin. The UKPDS study has confirmed metformin (Met) as the initial monotherapy. Accordingly, Met is widely regarded as the first drug of choice for most patients with T2DM. Safety and efficacy of sulphonylureas (SU) have been confirmed by several clinical trials. Recently, thiazolidinediones (TZD) have addressed some aspects of insulin-resistance that characterized several T2DM patients. However, SU and TZD are associated with various side effects that limit their use in many patients. New agents have been recently developed which potentiate the activity of the incretin (GLP1). GLP1, a gut hormone secreted in response to meal ingestion, is rapidly degraded by dipeptidylpeptidase-4 (DPP-4). GLP1 enhances insulin secretion and inhibits glucagon secretion in a glucose-dependent manner, delays gastric emptying and, in animal studies, preserves beta-cell mass by reducing apoptosis and stimulates of beta-cell proliferation. GLP1 levels are abnormally low in T2DM patients. Two classes of agents based on GLP1 have been launched: DPP-4 inhibitors and DPP-4 resistant GLP1 analogues. Randomized studies confirmed their efficacy to improve glycemic control in T2DM patients. Orally administered DPP-4 inhibitors reduce HbA1c by 0.5-1.1%, without hypoglycaemic events and no weight gain. The sub-cutaneous injected GLP1 analogues (exenatide and liraglutide) show larger reductions in HbA1c by 0.8-1.7% and weight loss but are associated with gastrointestinal side effects contributing to a significant treatment interruption. Several studies support the use of DPP-4 inhibitors in combination with Met as a promising second line treatment.

Cortico-responsive encephalopathy associated with autoimmune thyroiditis (SREAT): about two case reports characterized by a gap between the diagnosis of autoimmune thyroiditis and neurological disorders.

We report two cases of steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) often called "Hashimoto's encephalopathy" in which the neurological manifestations develop years before or after the Hashimoto's diagnosis. Because of this specific presentation, the etiological diagnosis of this type of encephalopathy can be a difficult task. In our patients there was a gap of 10 to 20 years between the proof of autoimmune thyroiditis and the neurological symptoms. Case reports of this type of presentation are rare in the literature. A dramatic responsiveness to steroids with total recovery, after several relapses, was confirmed 3 years after the end of treatment. We suggest that antithyroid antibodies should be checked in all patients with unexplained acute or subacute encephalopathy even in elderly subjects in whom the most important differential diagnosis with Creutzfeldt-Jacob disease remains rapidly progressive Alzheimer's disease. A brief review of the literature is proposed.