Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre-trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin.

AIMS: To assess whether people with type 2 diabetes transferring from higher basal insulin doses (> 20 units) to a starting dose of 16 units of insulin degludec/liraglutide (IDegLira) benefit from IDegLira with/without transient loss of glycaemic control. METHODS: Post hoc analysis of DUAL V and VII assessed fasting self-measured blood glucose (SMBG) over weeks 1-8, changes in HbA1c, body weight and mean insulin dose over 26 weeks, and percentage of participants achieving HbA1c < 53 mmol/mol (7.0%) by end of trial in participants with type 2 diabetes uncontrolled with basal insulin. IDegLira was compared with continued up-titration of insulin glargine (IGlar U100) in DUAL V, or switching to basal-bolus therapy in DUAL VII (IGlar U100 and insulin aspart), across pre-trial insulin dose groups (20-29, 30-39 and 40-50 units/day). RESULTS: In all subgroups, participants treated with IDegLira experienced significant improvements in HbA1c by end of trial, which were greater than with IGlar U100 up-titration (estimated treatment difference -5.86, -6.59 and -6.91 mmol/mol for pre-trial insulin doses of 20-29, 30-39 and 40-50 units/day, respectively) and similar to basal-bolus therapy (estimated treatment difference -0.16, -1.0 and -0.01 mmol/mol for pre-trial insulin doses of 20-29, 30-39 and 40-50 units/day, respectively). Compared with IGlar U100 and basal-bolus therapy, IDegLira participants experienced weight loss vs. weight gain, lower rates of hypoglycaemia and a lower mean end of trial total daily insulin dose. In both trials, mean fasting SMBG decreased from weeks 1 to 8 across all subgroups, despite a temporary increase in mean fasting SMBG in the 40-50 units pre-trial insulin dose group during week 1 [mean increase (sd) +1.1 (2.0) mmol/l for DUAL V and +1.1 (2.1) mmol/l for DUAL VII], which reverted to baseline by week 4. CONCLUSIONS: Regardless of pre-trial insulin dose, IDegLira resulted in improved clinical outcomes, even in participants transferring from 40-50 units of basal insulin, despite a transient (< 4 weeks), clinically non-relevant, elevation in pre-breakfast SMBG. (Clinical Trial Registry Number NCT01952145 and NCT02420262).

Practical implementation, education and interpretation guidelines for continuous glucose monitoring: A French position statement.

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care.

Frequency and predictors of confirmed hypoglycaemia in type 1 and insulin-treated type 2 diabetes mellitus patients in a real-life setting: results from the DIALOG study.

AIM: DIALOG assessed the prevalence and predictors of hypoglycaemia in patients with type 1 (T1DM) or insulin-treated type 2 diabetes mellitus (T2DM) in a real-life setting. METHODS: In this observational study, insulin-treated patients (n=3048) completed prospective daily questionnaires reporting the frequency and consequences of severe/confirmed non-severe hypoglycaemia over 30 days. Patients (n=3743) also retrospectively reported severe hypoglycaemia over the preceding year. RESULTS: In this prospective survey, 85.3% and 43.6% of patients with T1DM and T2DM, respectively, reported experiencing at least one confirmed hypoglycaemic event over 30 days, while 13.4% and 6.4%, respectively, reported at least one severe event. Hypoglycaemia frequency increased with longer duration of diabetes and insulin therapy. Strongly predictive factors for hypoglycaemia were previous hypoglycaemia, >2 injections/day, BMI<30kg/m(2) and duration of insulin therapy>10 years. HbA1c level was not predictive of hypoglycaemia in either T1DM or T2DM. The confirmed hypoglycaemia rate was increased in the lowest compared with the highest tertile of HbA1c in T1DM, but not T2DM. At the time of enrolment, physicians reported severe hypoglycaemia in 23.6% and 11.9% of T1DM and T2DM patients, respectively, during the preceding year; the retrospective survey yielded frequencies of 31.5% and 21.7%, respectively. Also, severe hypoglycaemia led to medical complications in 10.7% and 7.8% of events in T1DM and T2DM patients, respectively, over 30 days. CONCLUSION: Using a unique combined prospective and retrospective approach, the DIALOG study found a relatively high frequency of hypoglycaemia among insulin-treated patients. These findings emphasize the importance of a patient-centred approach for managing diabetes in which hypoglycaemia risk evaluation is critical. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01628341.

Nephrotic syndrome associated with chronic lymphocytic leukemia: an immunological and pathological study.

Three patients with B chronic lymphocytic leukemia and the nephrotic syndrome had atypical membranous glomerulonephritis or lobular membranoproliferative glomerulonephritis with subepithelial and subendothelial deposits containing IgG1 kappa, IgG1 lambda or IgM and IgG by immunofluorescence, respectively. A monoclonal cryoglobulin was intermittently found in the serum in one case. In two patients, kidney deposits were made of organized microtubular structures. Intracytoplasmic immunoglobulin inclusions in the two patients' lymphocytes showed a very similar electron microscopic pattern. The immunologic phenotype of leukemic lymphocytes was analogous in the three cases (with expression of CD2) and suggestive of a late maturation step. A complete remission of the nephrotic syndrome was observed after therapy with chlorambucil (and prednisone). These observations suggest a direct role of monoclonal immunoglobulins in kidney disease.

[Blink reflex and stimulus detection by the facial nerve in 21 diabetics. Testing before and after precise blood sugar normalization by the artificial pancreas]. / Réflexe de clignement et stimulodétection du nerf facial chez 21 diabétiques. Etude avant et après normalisation glycémique stricte par pancréas artificiel.

Study of the blink reflex and stimulodetection of the facial nerve in 21 diabetics with chronic hyperglycemia (HbA1C: 12.17 +/- 2.34%) shows normal or slightly prolonged R1, R2 and M latent periods in most cases. Forty-eight hour metabolic correction by artificial pancreas produces an overall improvement in the latent periods of the blink reflex, while the motor latent period of the facial nerve remained unchanged. The improvement, also observed in studies of limb responses, points towards a metabolic process directly related to the hyperglycemia.

[Remission induced at the early stage of insulin-dependent diabetes: do predictive factors exist?]. / Les rémissions induites à la phase précoce du diabète insulinodépendant: existe-t-il des facteurs prédictifs?

The induction of a remission has been attempted in 28 patients with insulin-dependent diabetes of less than 3 months' duration by strictly normalizing glycemia either with a period of external artificial pancreas followed by continuous subcutaneous insulin infusion (22 patients) or with continuous subcutaneous insulin infusion alone (6 patients). HLA A, B and DR antigens were determined in every patient. Residual beta-cell function was evaluated by measuring C peptide and the ratio of C peptide to glycemia, and by testing the response to a glucagon stimulation before initiating and after withdrawing insulin treatment. Oral treatment with 15 mg glibenclamide and 840 mg metformin daily was administered when insulin had been stopped. A remission was obtained in 17 of the 28 cases. The likelihood of a remission was greater if: (1) the patient was older (mean age was 25.6 years in case of success and 16.6 Years in case of failure); (2) initial daily needs for insulin were smaller (0.88 v. 1.23 U/kg); and (3) stimulated secretion of C peptide was larger (0.22 v. 0.11 mmol/l).

[Prognosis of generalized scleroderma. A retrospective study of 78 cases]. / Pronostic de la sclérodermie généralisée. Etude rétrospective de 78 observations.

From 1960 to 1984, 78 new patients with progressive systemic sclerosis were followed up: 60 women and 18 men whose ages ranged from 20 to 83 years, with a mean age of 58 years. Twenty nine are known to be dead and 3 were lost of follow-up. Forty six have been followed up to the present time for a mean period of 5 years. The cumulative survival rates were 88 +/- 7 p. 100 at one year, 62,5 +/- 11,5 p. 100 at five years and 50,5 +/- 15 p. 100 at ten years. These figures are significantly different from those found in a matched group from the French general population. Nine features at the time of diagnosis which might influence prognosis were studied. Seven factors apparently have not affected prognosis: sex, age, time elapsed between initial symptom and definitive diagnosis, location of scleroderma, blood pressure, erythrocyte sedimentation rate and creatinine clearance. On the other hand, survival declined significantly faster in the 28 patients with anemia than in the 50 patients without anemia (P less than 0,001). Similarly, the 47 patients with radiological pulmonary involvement or pulmonary function abnormalities were at significantly higher risk for death than the 31 patients without interstitial pulmonary fibrosis. Anemia and pulmonary involvement are predictors of mortality and important prognostic tools in the management of the different drugs that have been recommended for the treatment of patients with systemic sclerosis.

[Atypical Cogan's syndrome with cutaneous vasculitis: a case]. / Syndrome de Cogan atypique avec vascularite cutanée: une observation.

The authors report the case of a 81 years-old-woman who had simultaneously atypical Cogan's syndrome, cutaneous vasculitis and diverticular sigmoiditis. The relations being between these three diseases are discussed.

[Immunoblastic lymphadenopathy occurring during treatment with carbamazepine. 2 cases]. / Lymphadénopathie dysimmunitaire survenant au cours d'un traitement par la carbamazépine. Deux observations.

Dysimmune lymphadenopathies during carbamazepine treatment. A report of two cases. We report on two cases of dysimmune lymphadenopathies with histological aspect of angio immunoblastic lymphadenopathy (AIL) developing after administration of carbamazepine. Clinical manifestations consisted of fever, erythroderma, generalized pruritus, facial edema, lymphadenopathy, liver enlargement. The two patients had anemia, hypogammaglobulinemia, impaired liver function and a negative Coomb's test. Lymphocyte stimulation test with carbamazepine in vitro was positive in both cases. Lymph node biopsy disclosed the angioimmunoblastic proliferation characteristic of AIL. After discontinuing carbamazepine, a complete remission was obtained.

[Primary thyroid lymphoma: report of 8 cases]. / Lymphome malin primitif de la thyroïde: à propos de huit cas.

PURPOSE: Primary thyroid lymphoma (PTL) is a rare disease. Few patients are reported in the literature. We report eight new cases of PTL with long-term follow-up. RESULTS: The clinical presentation was usually an enlarging neck mass squeezing surrounding structures. The diagnosis was established after thyroidectomy with histopathologic and immunohistochemical studies. Histology showed infiltrates of chronic lymphocytic thyroiditis in all cases. Three patients had thyroid lymphoma arising from mucosa-associated lymphoid tissue. One patient died postoperatively. The other seven were treated with combined chemotherapy and radiotherapy. They were still in remission after a 6-year follow-up. CONCLUSION: Diagnosis of PTL should be suspected when there is a recent thyroid enlargement. Surgery associated with chemotherapy and radiation gave good results in our study with long-term follow-up, though surgery was not always recommended in previous reports.

[Does the direct immunofluorescence examination of superficial temporal artery biopsies have any value? Results of the study of 101 biopsies]. / L'examen en immunofluorescence directe des biopsies d'artères temporales superficielles présente-t-il un intérêt? Résultats de l'étude de 101 biopsies.

The lesions in temporal arteritis (TA) are known to be often segmental and the pathologic study of involved temporal arteries may be falsely negative. Several reports suggest that direct immunofluorescence (IF) may be of value in the diagnosis of the disease. We have studied by IF 101 consecutive biopsies from 100 patients investigated during the last two years. Adjacent segments were processed for light and immunofluorescent microscopy. For the latter, tissues were immediately frozen in liquid nitrogen and stored at -- 70 degrees C. Cryostat sections were stained with anti-gamma, alpha, mu, C3, fibrinogen and albumin conjugates. A sister section was also stained with HE for light microscopy. Deposits of Ig and/or C were either granular (intra- or extra-cellular) or linear closely applied to internal elastic lamina. The 100 patients fall into 4 groups: Group I, (19 patients) with diagnosis ascertained upon typical clinical record and clear cut anatomic lesions by light microscopy; Group II (10 patients) with the clinical features of TA and a negative biopsy by light microscopy; Group III (29 patients) in whom the diagnostic criteria of polymyalgia rheumatica were fulfilled according to Forestier and Certonciny; Group IV (42 patients) affected with various diseases unrelated to T.A. (1 with polyarteritis nodosa, 5 with rheumatoid arthritis...). The following results were obtained by IF: in group I, deposits were found in 63% of the patients studied (linear in 11 and granular in 4 cases). They included Ig usually with C3 and fibrinogen. In group II, we observed linear deposits of IgG in one patient and granular C3 deposits in another case.(ABSTRACT TRUNCATED AT 250 WORDS)

[Atypical echocardiographic aspects of cardiac amylosis]. / Aspects échographiques atypiques de l'amylose cardiaque.

Echographic abnormalities of cardiac amylosis are now well known and quite useful to the diagnosis. Forms that are morphologically atypical are rare. From three observations (2 hypertrophic, asymmetrical and obstructive forms, and 1 hypertrophic and dilated form) and a review from the literature, we study the nosological, diagnostic and therapeutic problems presented by these atypical echographic of cardiac amylosis.

[Detection of anti-double stranded DNA antibodies of IgG, IgA and IgM classes by ELISA. Comparison with the Farr test and indirect immunofluorescence]. / Détection des anticorps anti-ADN natif de classes IgG, IgA et IgM par ELISA. Comparaison avec le test de Farr et l'immunofluorescence indirecte.

Anti-double stranded DNA antibodies were measured by an immunoglobulin class-specific immunoenzymatic assay (ELISA), in 450 sera from 265 patients as well as by indirect immunofluorescence using Crithidia luciliae as a substrate and, for 124 sera, by the Farr test. ELISA proved specific and reproducible and it yielded results that were well correlated with the Farr assay, with a slightly higher sensitivity of ELISA. Correlation with immunofluorescence was not as good because of the lower sensitivity of the latter method. ELISA enables the levels and isotypes of anti-DNA antibodies to be determined. Both appear to be critical parameters for a clinical interpretation of results, especially with respect to the diagnosis of systemic lupus erythematosus.

[Chronic atrophic polychondritis. Critical analysis of the therapeutic efficacy of dapsone. 2 cases]. / Polychondrite chronique atrophiante. Analyse critique de l'efficacité thérapeutique de la dapsone. Deux observations.

Dapsone has been used since 1976 in the treatment of relapsing polychondritis. A critical analysis of its therapeutic effectiveness based on 2 personal cases and 14 cases reported in the literature, all treated with dapsone alone, showed that treatment had to be discontinued in 4 on account of side effects (haemolytic anaemia, erythema multiforme, somnolence, headache, nausea); 1 patient showed no improvement and 5 relapsed; 6 responded favourably and without relapse during a 3 months' to 4 years' follow-up. Considering the unpredictable course of relapsing polychondritis and the fact that some of its clinical manifestations, notably auricular chondritis, may spontaneously resolve, the response of the disease to dapsone is difficult to establish and requires to be confirmed by a controlled clinical trial.

[Prognosis of treated temporal arteritis. Retrospective study of 87 cases]. / Pronostic de l'artérite temporale traitée. Etude rétrospective de 87 observations.

Eighty-seven patients (mean age 73 years) with histologically proven Horton's disease were followed up in 5 different specialized hospital units from 1970 to 1984. Except for one patient treated exclusively with antimalarials, all were under corticosteroids. The mean initial dose of prednisone or equivalent was 0.7 mg/kg/day and the mean maintenance dose, 10 mg/day. Steroids could be discontinued in 21 cases after 36 months on average; the other patients could not be weaned, even though 4 of them had been on steroids for more than 10 years. Side-effects were noted in 43 cases. Twenty-four patients died, mostly of cardiovascular diseases. Survival rates were 89 +/- 6.35% at 1 year, 60.2 +/- 8.7% at 5 years and 48 +/- 11.3% at 10 years. In the long run, mortality in our series proved to be exactly the same as in the general population. Nineteen patients had ocular manifestations of giant cell arteritis always from the onset, except for a fall in visual acuity; 26 relapses were observed in 18 patients, either during reduction of steroid dosage (21 cases) or after withdrawal (5 cases). In 2 cases histology showed typical lesions of giant cell arteritis after 41 and 50 months respectively under corticosteroid therapy.