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.

Which oral antidiabetic drug to combine with metformin to minimize the risk of hypoglycemia when initiating basal insulin?: A randomized controlled trial of a DPP4 inhibitor versus insulin secretagogues.

We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.

Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Outcomes in women with a history of gestational diabetes. Screening and prevention of type 2 diabetes. Literature review.

Women with a history of gestational diabetes mellitus (GDM) are characterized by a high risk of type 2 diabetes mellitus (T2DM) (x 7), metabolic syndrome (x 2 to 5) and cardiovascular diseases (x 1,7). Women with lesser degrees of glucose intolerance share the same risks. T2DM may occur from post-partum (5 to 14%) to several years later, up to 25 years. Some factors associated with T2DM are identified: obesity, early diagnosis of GDM before 24 weeks gestation, high pregnancy OGTT blood glucose or insulin-therapy during GDM. Screening for T2DM only with fasting glucose provides less sensibility than with OGTT; HbA1c may supplant these dosages. The recurrence rate of GDM is between 30 and 84%, non-white ethnicity and insulinotherapy during GDM being the best proven predictors. High risk women need repeated life-long screenings for glycaemic abnormalities, or when another pregnancy is planned. Among obese women with history of GDM who show minor glycoregulation disturbances, modifications of lifestyle in intensive programs or metformin halve the risk of DT2. However, studies analysing practices show low adhesion to screening; without an intensive program, few women implement lifestyle modifications. These intensive programs should be implemented and proposed to high-risk women. Their therapeutic education should also include prevention of cardiovascular risk factors.

[Outcomes in women with history of gestational diabetes mellitus. Screening and prevention of type 2 diabetes mellitus. Literature review]. / Devenir maternel après un diabète gestationnel. Dépistage et prévention du diabète de type 2. Revue de la littérature.

Women with a history of gestational diabetes mellitus (GDM) are characterized by a high risk of type 2 diabetes mellitus (T2DM) (X 7), metabolic syndrome (X 2 to 5) and cardiovascular diseases (X 1,7). Women with lesser degrees of glucose intolerance share the same risks. T2DM may occur from postpartum (5 to 14%) to several years later, up to 25 years. Some factors associated with T2DM are identified: obesity, early diagnostic before 24 weeks, high pregnancy OGTT blood glucose or insulinotherapy. Screening for T2DM only with fasting glucose provides less sensibility than with OGTT; HbA1c may supplant these dosages. The recurrence rate of GDM is between 30 and 84%, non-white ethnicity and insulinotherapy during GDM being the best proven predictors. High risk women need repeated life-long screenings for glycemic abnomalies, or when another pregnancy is planned. Among overweight or obese women with history of GDM who show minor glycoregulation disturbances, it is proved that modifications of lifestyle in intensive programs or metformin halve the risk of DT2. However, studies analysing practices show low adhesion to screening; without an intensive program, few women implement lifestyle modifications. These intensive programs should be implemented and proposed to high-risk women. Their therapeutic education should also include prevention of cardiovascular risk factors.

Contribution of genetic analysis in screening for MEN1 among patients with sporadic disease and one or more typical manifestation.

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant hereditary syndrome (OMIM 131100) due to MEN1 gene mutations, predisposing to the development of hyperplasic and tumoral lesions of neuroendocrine tissues. Since the identification of the gene in 1997, more than 400 different mutations of MEN1 have been registered. Genotypic analysis of MEN1 remains fastidious and must be reserved to targeted situations. If the lesions appear in a familial assessed context, there is a strong argument to search for MEN1 mutation. This is not the case in a sporadic context. With experience acquired in our laboratory, we evaluated the frequency of MEN1 mutations in patients with sporadic presentations. Our aim was to better define criteria for MEN1 genotypic analysis. One hundred and twenty four blood samples from unrelated patients, who gave their written informed consent, were analyzed. These patients exhibited 1 to 4 manifestations of MEN1 without any familial context. After DNA extraction, the analysis was undertaken by PCR-sequencing of all the MEN1 coding exons and exon/intron boundaries or by PCR of the pre-screened fragments alone, a technique made possible by indirect screening mutation methods. Mutations were identified by comparing the sequences to the reference MEN1 sequence available from GENBANK (U93237.1). Mutations were identified in 19 patients, with variable prevalence according to clinical manifestations: 100% for patients with 4 manifestations, 45.5% for patients with 3 manifestations, 19% for patients with 2 manifestations and 2% for patients with only one manifestation. Mutations were: 11 point variations (58%), including 2 splicing sites and 8 frameshift mutations (42%) including 5 deletions, 2 insertions and 1 insertion/deletion; one mutation was identified twice. We showed a relationship between clinical presentation and MEN1 mutation identification, especially with the number of clinical manifestations but also with the type of manifestation. Pancreatic manifestations were significantly linked with probability of mutation. In a sporadic context with at least two established manifestations of MEN1, the overall probability of identifying a mutation was 26%, warranting MEN1 genotypic analysis.

Is pregnancy a risk factor for microvascular complications? The EURODIAB Prospective Complications Study.

AIMS: To examine the long-term influence of pregnancy on the development and progression of microvascular complications in Type 1 diabetes. METHODS: In the EURODIAB Prospective Complications Study (PCS), 793 women potentially child bearing at baseline completed the follow-up (7.3 years) and 163 (21%) gave birth during the follow-up period. We compared risk factors [mean levels of age, duration of diabetes, HbA(1c), systolic blood pressure (SBP) and proportion giving birth] between those that did or did not develop microvascular complications during the follow-up period. RESULTS: For the 425 childless women at baseline, 102 gave birth during follow-up. HbA(1c) was a significant risk factor for progression to microalbuminuria but age, duration of diabetes, systolic blood pressure or giving birth were not. Duration of diabetes and high HbA(1c) were significant risk factors for progression to proliferative retinopathy, whereas giving birth was not. Similar results were obtained for progression to any form of retinopathy. Giving birth was not significantly related to the incidence of neuropathy. Similar results were obtained for women with children at baseline giving birth during follow-up (n = 61/368). CONCLUSIONS: In this European study, having a first or another pregnancy did not seem to be a risk factor for long-term progression of any microvascular complication. This is in accordance with the findings of the Diabetes Control and Complications Trial (DCCT).

Higher carbohydrate intake is associated with decreased incidence of newborn macrosomia in women with gestational diabetes.

OBJECTIVE: To study the influence of energy and macronutrient intake on infant birthweight in women with gestational diabetes mellitus undergoing intensive management. DESIGN: This prospective study evaluated the impact of intensive management of gestational diabetes on maternal and fetal morbidity, and addressed the relationship between food intake and infant birthweight. SETTING: Fifteen maternity hospitals in northern France. SUBJECTS: Ninety-nine women with gestational diabetes or gestational mild hyperglycemia diagnosed between 24 and 34 weeks of gestation were surveyed. After 1 was excluded because of a premature birth and 18 were excluded as underreporters, 80 women were included in the final analysis. Diet intake was assessed by a dietary history at the first interview, and by two 3-day diet records at the 3rd and 7th week after diagnosis. RESULTS: In a forward-stepwise regression analysis (controlling for maternal age; smoking; parity; prepregnancy BMI; pregnancy weight gain; gestational duration; infant sex; fasting and 2-hour postprandial serum glucose; insulin therapy; and energy, fat, protein and carbohydrate intake during treatment) infant birthweight was positively associated with gestational duration (beta = +0.34, P<.002), and negatively with smoking (beta = -0.27, P<.02) and carbohydrate intake (beta = -0.24, P<.03). There were no large-for-gestational-age infants among women whose carbohydrate intake exceeded 210 g/day. CONCLUSION: For women with gestational diabetes undergoing intensive management, higher carbohydrate intake is associated with decreased incidence of macrosomia. APPLICATION: These findings suggest that nutrition counseling in gestational diabetes must be directed to maintain a sufficient carbohydrate intake (at least 250 g per day), which implies a low-fat diet to limit energy intake. A careful distribution of carbohydrate throughout the day and the use of low-glycemic index foods may help limit postprandial hyperglycemia.

Is mild gestational hyperglycaemia associated with maternal and neonatal complications? The Diagest Study.

AIMS: To evaluate the maternal and neonatal complications rates of mild gestational hyperglycaemia (MGH) compared to a control group in France. METHODS: A systematic screening by a 50-g glucose challenge test was offered to all women between 24 and 28 weeks of gestation in 15 maternity units. If the 50-g glucose challenge test was > or = 7.2 mmol/l, a 100-g 3-h oral glucose tolerance test (OGTT) was performed. MGH (n = 131) was defined by one abnormal value on the 3-h OGTT (Carpenter and Coustan criteria). The control group (n = 108) was defined by a 50-g glucose challenge test below 7.2 mmol/l. Women with MGH received no treatment or specific advice during the pregnancy. Large for gestational age (LGA) was defined by a birth weight of at least the 90th percentile on French standard growth curves. RESULTS: Women with MGH were older than the controls (28.8 (5.8) vs. 27.0 (5.2); P < 0.05) and had a higher body mass index (24.8 (4.8) vs. 23.0 (3.9); P < 0.01). The rate of pregnancy-induced hypertension and Caesarean section were not different between the MGH and control group. The rate of LGA was significantly higher in the MGH group than the control group (22.1% vs. 11.4%; P < 0.05). After adjustment for confounding factors of macrosomia (pre-pregnancy body mass index > 27, maternal age > 35, multiparity and educational level), there was a persistent relationship between LGA and MGH (odds ratio 2.50; 95% confidence interval (1.16-5.40); P < 0.05). MGH was more frequently associated with adverse maternal and fetal outcome than in the controls (53.4% vs. 28.7%; P < 0.01). CONCLUSIONS: This study suggested that the increased rate of adverse maternal and fetal outcome, especially LGA, was associated with untreated mild gestational hyperglycaemia women compared to a control group. This link to lower degrees of hyperglycaemia during pregnancy is independent of confounding factors.

Gestational diabetes mellitus and HLA class II (-DQ, -DR) association: The Digest Study.

Gestational diabetes mellitus (GDM) and impaired glucose tolerance during pregnancy (IGT) are associated with an increased risk of perinatal morbidity and then further development of diabetes among 30-50% of affected women. This is a real public health problem that deserves investigation of phenotypic and genotypic predisposing markers. However, the involvement of genetic background in GDM and IGT remains unclear. In particular, association with HLA class II polymorphism has been poorly studied and has produced conflicting results. In attempt to clarify these discrepancies, we investigated HLA class II polymorphism in 95 GDM and 95 IGT women from the north of France using DNA amplification followed by restriction enzyme digestion (PCR-RFLP). Ninety-five pregnant women with normal glucose tolerance (NGT) were chosen as a control reference group. The distribution of HLA class II polymorphism was not found to be significantly different between GDM, IGT and NGT samples. In particular, we did not find any significant variation of DRB1*03 and DRB1*04 allele frequencies between these three groups. These data provide further evidence that insulin-dependent diabetes mellitus (IDDM) HLA class II susceptibility alleles cannot serve as genetic markers for susceptibility to glucose intolerance during pregnancy. However, GDM and IGT were not equivalent to the NGT control group and presented particular HLA patterns. In particular, we observed an increase of the DRB1*0701-DQA1*0201-DQB1*02 haplotype in GDM women (P = 0.02; Pc not significant) and an increase of DRB1*0101-DQA1*0101-DQB1*0501 and DRB1*1302-DQA1*0102-DQB1*0604 haplotypes in the IGT group (P = 0.02 and 8 x 10(-3), respectively; Pc not significant). In contrast, we found a decrease in the DRB1*1101 allele in IGT samples (P = 0.03; Pc not significant) and a decrease of DRB1*1103-*1104 alleles in the GDM group (P = 9 x 10(-3); Pc not significant). Although these findings are only descriptive, it points out the genetic heterogeneity of glucose intolerance during pregnancy.

[Selective control of different hypophysial secretions by long-lasting pharmacodynamic agents. Analogs of somatostatin and LHRH and long-lasting bromocriptine]. / Principes du contrôle sélectif des différentes sécrétions hypophysaires par des agents pharmaco-dynamiques à effet retard. Analogues de la somatostatine, analogues de la LH-RH--bromocriptine retard.

The biological activity of the natural somatostatin can be quantitatively and qualitatively altered by the substitution and/or the exclusion of some of its amino-acids. The most used synthetic analog, SMS 201-995, has a potent inhibiting effect on GH secretion, but is less effective on insulin and glucagon secretions. It is mainly used in Endocrinology for the treatment of acromegaly. It is also useful for inhibiting the inappropriate TSH secretion from a thyrotroph adenoma. The LH-RH agonists ast essentially by desensitizing the gonadotroph from the endogenous LH-RH. By sub-cutaneous, intra-muscular or nasal route, they allow to inhibit the gonadal functions in some hormone-dependent cancers and in true precocious puberty. More recently, they have been tested for the treatment of gonadotropic adenomas, where they may have sometimes a paradoxical effect. In combination with exogenous gonadotropins, they enhance the control of ovulation and are new valuable tools for IVF programs. Clinical studies with the LH-RH antagonists are just beginning. The long-acting bromocriptine affords a new alternative to the oral treatment of hyperprolactinaemia. Its suppressive effects lasts at least 35 days in normal subjects and 21 days in patients with macroprolactinomas.