Disagreement between capillary blood glucose and flash glucose monitoring sensor can lead to inadequate treatment adjustments during pregnancy.

OBJECTIVE: Continuous glucose monitoring tends to replace capillary blood glucose (CBG) self-monitoring. Our aim was to determine the agreement between CBG and a flash glucose monitoring system (Flash-GMS) in treatment decision-making during pregnancy. RESEARCH DESIGN AND METHODS: Insulin-treated women with either type 1 (n=25), type 2 (n=4) or gestational diabetes (n=4) were included. A Flash-GMS sensor was applied for 14 days. Women scanned the sensor whenever they monitored their CBG. The primary endpoint was the proportion of discordant therapeutic decisions they would have made based on Flash-GMS rather than CBG results. Glucose averages, mean absolute difference (MAD), mean absolute relative difference (MARD) and Flash-GMS accuracy were also estimated. RESULTS: Data for forty 14-day periods were available. Preprandial Flash-GMS and CBG values were 93±42mg/dL and 105±45mg/dL, respectively (P<10-4), and 2-h postprandial (PP) values were 106±45mg/dL and 119±47mg/dL, respectively (P<10-4). MAD was 14±22mg/dL preprandial and 15±24mg/dL 2-h PP; MARD was 19%; and 99% of glucose value pairs were within the clinically acceptable A and B zones of the Parkes error grid. Concordance rate for therapeutic decision-making was 80-85% according to ADA targets and 65-75% according to a pragmatic threshold. At different time points of the day, 83-92% of discordant results were due to Flash-GMS values being lower than their corresponding CBG values. CONCLUSION: Flash-GMS tends to give lower estimates than CBG. Thus, in cases requiring therapeutic changes to treat or prevent hypo- or hyperglycaemia, 25-35% of choices would have been divergent if based on Flash-GMS rather than CBG.

Telemedicine and type 1 diabetes: is technology per se sufficient to improve glycaemic control?

AIM: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c? METHODS: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels. RESULTS: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084). CONCLUSION: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations.

Poor prognosis of pregnancy in women with autoimmune type 1 diabetes mellitus masquerading as gestational diabetes.

AIM: To describe the clinical presentation and the prognosis of autoimmune type 1 diabetes (T1D) that was first revealed during pregnancy masquerading as gestational diabetes mellitus (GDM). METHODS: We reviewed the files of 21 women in whom diabetes was revealed during a pregnancy ("index pregnancy") and progressed to T1D after delivery, and in whom GAD and/or IA-2 autoantibodies were found. RESULTS: The median age and BMI of the women were 31 years and 19.8 kg/m(2). Eleven women had at least one risk factor for GDM. Eight of the 12 multiparous women had had an abnormal outcome of previous pregnancy, including GDM in five. GDM was diagnosed at week 26 (range: 4-38) of gestation by screening in 18, because of macrosomia in two and during hyperglycaemic crises in three. All were treated with insulin, from the time of diabetes diagnosis in 10 and after 4 weeks (range: 2-15) in 11. Term of delivery was 38 (range: 26-41) weeks. Abnormal outcomes occured in 14 pregnancies, including two fetal deaths, four preterm deliveries and eight macrosomic infants. No congenital malformations were reported. After delivery, insulin therapy was stopped in 18 women for 6 months (range: 2-48). The diagnosis of the autoimmune origin of diabetes was established during the index pregnancy in only eight cases. CONCLUSION: T1D may reveal as GDM in women with or without risk factors for GDM and is associated with a poor prognosis, partly because the correct diagnosis and treatment are delayed. Whether screening for autoimmune markers of T1D should be performed more systematically in women with GDM deserves to be studied.

Familial young-onset forms of diabetes related to HNF4A and rare HNF1A molecular aetiologies.

OBJECTIVE: We have dissected the rare molecular anomalies that may affect hepatocyte nuclear factor-1a (HNF1A) and hepatocyte nuclear factor-4a (HNF4A) in patients with familial young-onset diabetes for whom HNF1A mutations have been excluded by sequence analysis. METHODS: Eighty-four unrelatedHNF1A-negative patients with diabetes diagnosed before the age of 40 years, a family history of diabetes and the absence of features suggestive of Type 2 diabetes were included. We analysed by sequencing the HNF4A promoter and coding regions, the HNF1A promoter region and specific regions of HNF1A(B) and HNF1A(C) isoforms and searched for large deletions of HNF1A and HNF4A by multiplex ligation-dependent probe amplification (MLPA). RESULTS: We identified five novel HNF4A mutations (5 / 84, 6%), including four missense and one in-frame deletion, and one mutation of the HNF1A promoter (1 / 84). Sequence analysis of isoform-specific coding regions of HNF1A did not reveal any mutation. We next identified two whole gene deletions of HNF1A and HNF4A, respectively (2 / 84, 2.4%). CONCLUSIONS: Altogether, the search for rare molecular events in HNF1A and HNF4A led us to elucidate 8 / 84 (9.5%) of our HNF1A-negative cases.This study shows that genetic aetiologies remain to be elucidated in familial young-onset diabetes. It also highlights the difficulty of the differential diagnosis with Type 2 diabetes because of the wide clinical expression of monogenic young-onset diabetes and the absence of specific biomarkers.

Information and therapeutic education of diabetic patients in French hospitals: the OBSIDIA survey.

AIM: Although several studies have evaluated the efficacy of therapeutic education (TE) programmes in patients with diabetes and demonstrated the benefits of such interventions, operational aspects are rarely described. For this reason, this national survey was conducted to investigate TE in France, and to identify its obstacles and needs. METHODS: A preliminary qualitative phase was extended to include a quantitative survey through face-to-face interviews, followed by a web-based self-administered questionnaire sent out to every healthcare professional dealing with diabetic patients. RESULTS: From the expanded web-based survey, 272 questionnaires were analyzed (39% from academic hospitals, 54% from general hospitals and 7% from private clinics); 85% of these sites provided TE for inpatients. Overall, TE was offered to 66% of patients (84% new patients) and was individualized in 55% of cases, and involved 9.4 healthcare professionals on average, with physicians, nurses and dietitians making up the core team. The TE offered encompassed a wide range of diabetes topics. However, of every 10 healthcare professionals, only 35% received specific training, while 45% received coaching from their colleagues and 10% received no training at all. Evaluation of TE was carried out in 60% of teams by questionnaires or interviews. CONCLUSION: TE is well implemented in French hospitals, but lacks homogeneity and standardization. Training is inadequate from both qualitative and quantitative points of view, and evaluation of TE procedures needs to be developed. There is also a need for more funding and dedicated qualified staff, a lack of which is partly due to the fact that TE is not a recognized medical activity in hospitals.

How patients' attitudes and opinions influence self-care behaviours in type 2 diabetes. Insights from the French DIABASIS Survey.

AIM: This study evaluated the profiles of patients with type 2 diabetes (T2DM) to identify sets of opinions and attitudes towards the disease that might influence self-care behaviours. METHODS: Altogether, 1,092 patients with T2DM, aged 45 or older from a large representative French cohort, completed a self-questionnaire exploring their knowledge and perceptions of diabetes, its impact on various aspects of daily life and self-management practices. Canonical and cluster analyses were used to identify sets of homogeneous 'profiles' of patients linking attitudes and opinions to specific disease-related behaviours (such as changes in lifestyle, drug compliance, treatment satisfaction, impact on everyday life and weight gain). RESULTS: Demographics of the T2DM study population were previously reported along with the main results (60% male; mean age: 66 years; mean age at diagnosis: 55 years; mean BMI: 29kg/m(2)). Five distinct patient types emerged from the typological approach: 'committed' (25%); 'carefree' (23%); 'bitter' (19%); 'disheartened' (19%); and 'overwhelmed' (15%). Each patient type defined a set of attitudes and beliefs towards T2DM that influenced disease-related behaviours, leading to different degrees of diabetes self-management. CONCLUSION: The DIABASIS survey provides important information for diabetes care by identifying distinct patients' profiles that express different degrees of difficulty in implementing self-management. For this reason, patients in each category require different kinds of customized support from their physician to induce behavioural changes that may be key in improving their metabolic control.

How do patients with type 2 diabetes perceive their disease? Insights from the French DIABASIS survey.

AIM: The main purpose of this survey was to describe type 2 diabetes (T2DM) from the patient's standpoint in a representative French panel in 2008. METHODS: Fourteen thousand two hundred and one individuals from the general population aged 45 or older completed a self-questionnaire exploring knowledge about diabetes; 1092 replies were from patients with T2DM. RESULTS: The prevalence of T2DM in this population was 7.7%, with demographics as follows: 60% men; mean age: 66 years; mean age at diagnosis: 55 years; mean BMI: 29 kg/m(2). Eighty-five percent of T2DM patients reported that they wanted more information about at least one aspect of the disease at diagnosis; they reported feeling anxious (30%), frightened (13%), angry (4%) or that the disease was unfair (12%). Half of the patients had modified their dietary habits but 71% found it difficult to engage in regular physical activity. Most patients (90%) were treated with drugs: 81% with oral antidiabetic drugs (OAD) (44% in monotherapy) while 19% received insulin (alone or in combination with OAD). Twenty-three percent complained of weight gain since start of current therapy (average gain of 7.3 kg). Insulin initiation represented a turning point for patients who became more aware of the disease severity, more willing to follow advice and to take greater control over their disease management. The mean time from diagnosis to insulin initiation was 13.8 years. Half of the patients perceived their disease as severe especially women, patients who initially reacted with anxiety, insulin-treated patients and those actively involved in their disease management. Some gender differences emerged: women took the disease more seriously, were more engaged in self-management, and reported a higher impact on daily life. CONCLUSIONS: DIABASIS provides important information for diabetes care by highlighting patients' views of the disease, such as distress at diagnosis, lack of adequate information to cope with this distress and the important supportive role played by the family. A deeper understanding of patients' perception of the disease would help optimize customized care.

Advantages to using capillary blood beta-hydroxybutyrate determination for the detection and treatment of diabetic ketosis.

Ketone body determination is indicated in all diabetic patients when the risk of ketotic decompensation exists. New methods of screening for ketosis, in particular capillary blood ketone body determination, provide analytical, technical and clinical advantages compared to the conventional ketonuria. It is proposed that a diabetic patient with hyperglycaemia (capillary blood glucose > 2.50 g.l(-1)) and capillary blood ketone bodies exceeding 0.5 mmol.l(-1) requires therapeutic management. For values greater than 3 mmol.l(-1) or in case of more serious clinical symptoms, hospitalisation is indicated, considering the high probability of ketoacidotic decompensation. The advantages of capillary blood ketone body determination including easy use, and rapid and objective results may improve management of the diabetic patient, especially in emergency situations. However, prescription by a physician of capillary blood ketone body determination should be offered to targeted populations that have a high risk of ketoacidotic decompensation, after providing education to patients that is above all aimed at preventing this metabolic complication. In this context of determining ketone bodies in capillary blood, the term "capillary blood ketone bodies" is therefore preferable to the term "capillary blood beta-hydroxybutyrate determination". Indeed, it appears more appropriate, simple, descriptive and significant both for health-care staff and for patients.

[Indications and modalities of assisted reproductive techniques in infertile women with cystic fibrosis]. / Mucoviscidose féminine et projet d'enfant: spécificités des indications et résultats de l'aide médicale à la procréation.

OBJECTIVE: To treat cystic fibrosis women who failed to conceive. PATIENTS AND METHODS: Multidisciplinary coordinated approach in 20 infertile women affected with cystic fibrosis. Advisability of pregnancy was based on the assessment of pulmonary and nutritional status, risks of maternal health deterioration, infertility factors, risk of cystic fibrosis in the offspring. Assisted reproductive techniques in moderately affected women are described. RESULTS: Three patients requested only information, three were discouraged, two are still evaluated, 12 were treated and three delivered healthy children. The pulmonary status of each patient remained unchanged 36 months after delivery, and all three children remain healthy. DISCUSSION AND CONCLUSION: Assisted reproductive techniques are an option in moderately affected infertile cystic fibrosis women. Advisability and management of pregnancy should be provided by a coordinated team of healthcare professionals with knowledge and experience in cystic fibrosis.

[Diagnosis and treatment of diabetes in adult patients with cystic fibrosis]. / Diagnostic et traitement du diabète chez les patients adultes atteints de mucoviscidose.

As their life expectancy has improved, patients with cystic fibrosis have experienced an increasing incidence of diabetes. Diabetes mellitus is characterized by improved and delayed insulin secretion, normal insulin sensitivity, and it is most often accompanied by exocrine pancreatic insufficiency. The development of diabetes mellitus is insidious and symptomless, and the overall cystic fibrosis status deteriorate for years prior to the diagnosis of diabetes. Since insulin therapy seems to revert deterioration for years of clinical status, and since late diabetic complications may develop, diabetes mellitus in cystic fibrosis should be identified by screening with an OGTT from the age of 15 years, and treated with insulin from the time of diagnosis of diabetes.

[Metabolic complications associated with use of protease inhibitors]. / Problèmes métaboliques observés sous traitement par antiprotéases.

The potency of highly active antiretroviral therapy, including protease inhibitors have led to declining morbidity and mortality in patients with HIV infection. However the use of protease inhibitors is associated with onset of morphologic and metabolic disorders. A syndrome of lipodystrophy has been described. It is characterized by fast wasting of the face and limbs, and a central adiposity, breast hypertrophy and buffalo neck. The prevalence of lipodystrophy in patients treated with protease inhibition is about 60%. The principal metabolic disorders are lipid abnormalities, principally hypertriglyceridemia. New onset of diabetes mellitus is less frequent. The pathogenesis of these abnormalities unknown. Insulin resistance seems to be a common feature of protease inhibitor associated metabolic an morphologic side-effects.

[Adrenal incidentalomas]. / Fortuitomes surrénaux.

Since the early 1980s, incidentally discovered adrenal masses have become a common clinical problem as a result of the more widespread use of abdominal imaging procedures. Once identified, an adrenal lesion must be characterized as to its functional status and malignant potential. The evaluation of these masses include clinical, hormonal, radiological and scintigraphic data. Optimal treatment of these patients require an agreement between endocrinologist, radiologist and surgeon. The presence of an hypersecretion will prompt a surgical intervention. In the vast majority of cases, the mass will be hormonally nonhypersecretory. Than the possibility of primary or metastatic malignancy must be excluded. The arguments for benign nonhypersecretory mass are mainly a enhanced CT attenuation coefficient of 0 HU or less, a small size (< or = 3 cm of diameter), typical feature of benign mass on CT scan. In the presence of those features non further investigation are necessary, and a reevaluation will be done regularly. We recommended surgery for adrenals at high risk of malignancy: 1. CT attenuation coefficient of more than 10 HU; 2. large (> 5 cm) diameter or increase in size at any reevaluation; 3. picture of intratumoral necrosis, hemorrhage or irregular margins.

[Cushing's disease]. / Maladie de Cushing.

Patients with Cushing's disease usually present typical clinical and biological features easily leading to the diagnosis. However very atypical presentations of the disease do exist especially in the intermittent forms and several investigations are often necessary to detect pituitary microadenoma wich sometimes is inconspicuous. The course of the disease can be serious and might responsible of definitive sequellas wich can threaten patient's life. Therefore rapid treatment is recommended. Pituitary surgery should be considered as the major therapeutic approach; however, in severe cases or when pituitary-directed treatments or OP'DDD have failed, total bilateral adrenalectomy should be proposed.

[Riedel's thyroiditis and lymphoma. Diagnostic difficulties]. / Thyroïdite de Riedel et lymphome. Difficultés diagnostiques.

Two cases of Riedel's thyroiditis demonstrated the difficulties encountered in diagnosis. In the first case, subtotal thyroidectomy was performed due to compressive goiter. The intraoperative macroscopic aspect suggested Riedel's thyroiditis. The pathology report also discussed the diagnosis, despite a major lymphoid component, as dense fibrosis had multilated the thyroid parenchyma. Subsequent clinical course led to the diagnosis of lymphoma. The clinical presentation in the second case was classical with rapid increase in size of a hard thyroid gland. Histology was however atypical showing calcifications and liquid cysts within the fibrous thyroid tissue. The initial signs of Riedel's thyroiditis, a very rare disease, usually suggest neoplasia: ligneous compressive goiter with deep adherences. Histologically, there is invasive fibrous thyroiditis with highly suggestive occlusive phlebitis in certain cases. The origin of the disease remains obscure. The differential diagnosis between a sclerosing form and lymphoma is particularly important for therapeutic management.

Long-distance and long-term follow-up of a patient with intermittent Cushing's disease by salivary cortisol measurements.

Salivary cortisol is an excellent indicator of the plasma free cortisol concentration in normal and pathological situations. We took advantage of its ease of sampling, allowing multiple collections at home, to follow the course of a patient with Cushing's disease living in North Africa. This 48-year-old woman presented with a clinically moderate hypercortisolism caused by a large basophilic pituitary adenoma. Bilateral extension to the cavernous sinuses precluded surgical therapy. She went into spontaneous remission based on clinical signs as well as biochemical findings. During the following 2 years she demonstrated intermittent relapses that were treated by radiotherapy (50 Gy), followed by ketoconazole and then o-paraprime-dichloro-diphenyl-dichloroethane (Op'DDD). After a prolonged clinical remission, Cushing's syndrome again became active. Bromocriptine was started without effect and a new treatment with Op'DDD was began. Evaluation and follow-up were performed during hospitalizations and mainly through the measurements of salivary cortisol in more than 100 samples sent from North Africa by air mail to our department in Paris. Thus we were able to demonstrate intermittent overproduction of cortisol before any treatment, with periods of normal and even low values, and to follow the efficacy of therapy and to detect the relapses. We conclude that measurement of salivary cortisol is a valuable tool in difficult clinical situations such as intermittent hypercortisolism and remoteness between the patient and hospital.

[Bilateral adrenal tumoral formation. Regressive spontaneous evolution]. / Formation tumorale surrénalienne bilatérale. Evolution spontanée régressive.

A case of bilateral adrenal tumoral formation associated with Addison's disease is reported, and the possible cause of this association is discussed. The short-term deleterious course of metastatic malignancies, hemopathies or severe infections when left without specific treatment, and the long-term course of our patient's tumoral pathology excluded these diagnoses. The spontaneous regression of a bilateral pseudotumoral mass was suggestive of 2 causes: haematoma or tuberculosis. Haematoma was unlikely in the absence of causal factors, and this, combined with the slow regression of the adrenals, made tuberculosis the most probable diagnosis. The few similar cases found in the literature are reviewed.

[Effects of deprivation and replacement by percutaneous 17 beta estradiol and oral progesterone on blood pressure and metabolic parameters in menopause patients with non-insulin-dependent diabetes]. / Effets de la substitution par 17 beta estradiol percutané et progestérone orale sur la pression artérielle et les paramètres métaboliques chez des patientes ménopausées diabétiques non insulinodépendantes.

The main purpose of this randomized controlled study was to assess the effects of postmenopausal estrogen replacement therapy on blood pressure (BP) and plasma renin substrate (PRS) in non insulin-dependent diabetic patients (DNID). We randomized 32 postmenopausal DNID (mean age: 55.3 +/- 4.2 years) into two groups: 16 women were untreated, and 16 received percutaneous estradiol (E2) 17 beta and natural progesterone for 6 months. Systolic (SBP) and diastolic (DBP) blood pressure were monitored by an automatic device at inclusion and on the 1st, 3rd and 6th months of therapy. Treatment efficacy was proven by significant E2 plasma increase to 92.2 +/- 13.4 pg/ml in the treated group, which is a sufficient level for preventing postmenopausal osteoporosis. No significant inter or or intra-individual variation in SBP or DBP was observed in either group. The same stability was noted for plasma renin substrate. No significant difference was noted between the two groups in terms of body weight, fructosamine and glycosylated hemoglobin A1c after 1, 3 and 6 months. There was also no change in plasma levels of total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and apolipoproteins A1 and B. All the patients who received replacement therapy wished to continue treatment. We conclude that the association of percutaneous E2 17 beta and natural progesterone had no deleterious effects, in diabetic patients, on BP, carbohydrate and lipoprotein metabolism. Thus this postmenopausal replacement therapy appears preferable in this vascular high risk population, particularly since estrogens via the parenteral route may have an antiatherogenic effect by direct action on the vessel walls.