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.

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.

Incidence and characteristics of lower limb amputations in people with diabetes.

AIMS: To estimate the incidence, characteristics and potential causes of lower limb amputations in France. METHODS: Admissions with lower limb amputations were extracted from the 2003 French national hospital discharge database, which includes major diagnoses and procedures performed during hospital admissions. For each patient, diabetes was defined by its record in at least one admission with or without lower limb amputation in the 2002-2003 databases. RESULTS: In 2003, 17 551 admissions with lower limb amputation were recorded, involving 15 353 persons, which included 7955 people with diabetes. The crude incidence of lower limb amputation in people with diabetes was 378/100 000 (349/100 000 when excluding traumatic lower limb amputation). The sex and age standardized incidence was 12 times higher in people with than without diabetes (158 vs. 13/100 000). Renal complications and peripheral arterial disease and/or neuropathy were reported in, respectively, 30% and 95% of people with diabetes with lower limb amputation. Traumatic causes (excluding foot contusion) and bone diseases (excluding foot osteomyelitis) were reported in, respectively, 3% and 6% of people with diabetes and lower limb amputation, and were 5 and 13 times more frequent than in people without diabetes. CONCLUSIONS: We provide a first national estimate of lower limb amputation in France. We highlight its major impact on people with diabetes and its close relationship with peripheral arterial disease/neuropathy and renal complications in the national hospital discharge database. We do not suggest the exclusion of traumatic causes when studying the epidemiology of lower limb amputation related to diabetes, as diabetes may contribute to amputation even when the first cause appears to be traumatic.

Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7-8% A1c levels. The TULIP study.

AIM: To determine whether earlier administration of insulin glargine (glargine) vs. the intensification of lifestyle management (LM) improves glycaemic control in type 2 diabetes patients with A1c 7-8% treated with oral therapy. METHODS: TULIP [Testing the Usefulness of gLargine when Initiated Promptly in type 2 diabetes mellitus (T2DM)] was a 9-month, 12-visit, open-label, multinational, multicentre, randomized study to evaluate starting glargine or intensifying LM in T2DM patients aged 40-75 years, body mass index (BMI) 24-35 kg/m2 and A1c 7-8%, treated with maximum doses of metformin and sulphonylurea for > or = 2 years. Glargine was injected once daily (evening) and titrated to fasting blood glucose 0.7-1.0 g/l. In the LM arm, dietary and physical activity counselling recommended stable weight for people with BMI < 27 kg/m2 or weight loss of 3 kg for patients with BMI > or = 27 kg/m2. A total of 215 patients were randomized to glargine (n = 106) or LM (n = 109). The primary objective was patients achieving A1c < 7% at endpoint. Secondary endpoints included changes in A1c, in fasting plasma glucose (FPG), body weight and hypoglycaemia incidence. RESULTS: Two hundred and eleven (52.6% male) patients were randomized and treated; mean (+/- s.d.) age 60.7 +/- 7.9 years, weight 84.5 +/- 13.1 kg, BMI 29.9 +/- 3.5 kg/m2 and A1c 7.6 +/- 0.4%. More patients reached A1c < 7% (66 vs. 38%; p < 0.0001) or < 6.5% (34 vs. 11%; p = 0.0001) with glargine vs. LM. The change in FPG from baseline to study endpoint was significantly greater in the glargine vs. the LM arm (-0.50 +/- 0.47 vs. -0.05 +/- 0.39 g/l respectively; p < 0.0001). Compared with the glargine group, the LM group showed a decrease in weight (+0.9 +/- 2.9 vs. -2.5 +/- 3.2 kg; p < 0.0001), as well as the expected lower symptomatic hypoglycaemia (55.3 vs. 25.0%; p < 0.0001) and nocturnal hypoglycaemia (20.4 vs. 5.6%; p = 0.0016). No significant changes were observed from baseline to study endpoint in any of the lipid parameters tested. CONCLUSIONS: In patients with T2DM with A1c 7-8%, who were previously treated by conventional LM and OAD therapy, adding glargine resulted in greater improvements in glycaemic control vs. intensifying LM.

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.

Should diabetic patients be asked to test their blood glucose 90 to 120 minutes after the beginning of their meals?

There are three distinct objectives in reducing the post-prandial blood glucose peaks: 1st to reduce the risk of foetal macrosomia in pregnancy, 2nd to reduce cardiovascular morbi-mortality, 3rd to lower the HbA1c. With 6-7 glycaemic controls per day and fractionning their meals, motivated women with gestational diabetes reach this goal. But there is no data today directly proving that post-prandial glycaemia is specifically related to the development of micro and macrovascular complications. So to reduce the cardiovascular risk, there are more arguments in favour of lowering HbA1c or prescribing statins than in prescribing a hypoglycaemic drug acting selectively on post-prandial glycaemia. Lastly, to reduce HbA1c near to the goal of 7%, the most important is to reduce the preprandial glycaemia below 1.20 g/l. The patients must be required to monitor their post-prandial glycaemia 2 hours after the beginning of the meal only when the aim is to lower the HbA1c below 7% or 6.5%, for example during pregnancy, or in case of discrepancy between glycaemia at 8 a.m. and 7 p.m. (below 1.20 g/)l and HbA1c (above 7%). In other cases, in type 2 diabetes, two glycaemias per day, fasting and vesperal, seems sufficient.

Elevated circulating levels of matrix metalloproteinase-9 in type 1 diabetic patients with and without retinopathy.

OBJECTIVE: Tissue expression pattern of matrix metalloproteinases (MMPs) and their inhibitors TIMPs indicate that microvascular complications of diabetes mellitus are associated with extracellular matrix remodelling. We investigated whether circulating levels of MMP-9 and TIMP-1 are altered in diabetic retinopathy and whether they might serve as biological markers of ocular complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: We recruited 47 type 1 diabetic patients free of vascular complications (n=40) or with retinopathy (n=14). Patients with macroangiopathy, neuropathy and nephropathy were excluded. A group of nondiabetic control subjects (n=35) was also constituted for comparative purposes. Peripheral blood levels of MMP-9 and TIMP-1 were determined using immunoenzymatic assays. RESULTS: Type 1 diabetic subjects exhibited significantly higher circulating levels of both MMP-9 and MMP-9/TIMP-1 ratio, as well as a tendency to increased serum TIMP-1 levels relative to nondiabetic controls (p<0.001). Diabetic patients with retinopathy also displayed elevated systemic values of MMP-9 and MMP-9/TIMP-1 ratio when compared to patients without retinopathy (p<0.05). Logistic regression analysis identified diabetes duration firstly (P<0.01), and MMP-9 serum levels secondly (P<0.01) as significant and independent variables associated with the existence of retinopathy. CONCLUSIONS: Our data suggest that peripheral blood MMP-9 levels might serve as surrogate biomarkers of retinopathy in type 1 diabetic patients free of other vascular complications.

Limitations of the so-called "intensified" insulin therapy in type 1 diabetes mellitus.

Intensive insulin treatment is defined by basal-prandial insulin therapy which tries to reproduce physiological insulin secretion. This requires 3 to 5 injections and self-monitoring of blood glucose 4 to 5 times a day. Patients who accept their disease and the demanding treatment regimen most often achieve HbA1(c) < 7.5%. Severe complications of diabetes can be avoided without increasing the risk of severe hypoglycemia. However, 50% of type 1 diabetic patients do not reach this objective. The reasons are: the disease itself, the diabetic patient, or the physician. Brittle diabetes with severe, repeated episodes of hypoglycemia and inversely persistent postprandial hyperglycemia prevents patients from reaching the ideal glycemic target. More often, the main obstacle is related to psychological problems: difficulties in self-regulation, denial of the disease, or phobia of hypoglycemia with avoidance behavior. Frequently, young women present eating disorders which can explain the poor diabetes control. The physician himself may be implicated in these poor glycemic results by not prescribing the right tools to obtain optimal glycemic control (staying with just two daily injections with premixed insulin) or by assigning glycemic targets inaccessible for the patient, or when an empathic relationship cannot be established between the patient and the physician. Patient empowerment is the key to the success of functional insulin treatment.

Percutaneous transluminal angioplasty in severe diabetic foot ischemia: outcomes and prognostic factors.

OBJECTIVES: To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were sought. RESEARCH DESIGN AND METHODS: In 32 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTA was performed if feasible; if not, primary bypass grafting was done when feasible. All patients were followed until healing or for at least one year. Patients with worsening ulcers after PTA underwent bypass grafting. Clinical and angiographic factors influencing outcomes after PTA were sought by univariate and multivariate analysis. RESULTS: PTA was done in 25 of the 32 (78%) patients, and considered clinically successful in 13 (52%). After 1 year, the healing rate was 70% and the limb salvage rate 90%. Successful PTA was significantly associated with a higher post-PTA transcutaneous oxygen pressure (P = 0.03) and presence of at least one patent pedal vessel (P = 0.03) in the univariate analysis; only a patent pedal vessel was significant in the multivariate analysis. CONCLUSION: Primary PTA in diabetic patients with severe ischemic foot ulcers provides similar outcomes to usual results obtained in severe ischemia in absence of diabetes. The presence of one patent pedal vessel on arteriography before PTA is the best prognostic factor.

Inhibition of insulin gene expression by long-term exposure of pancreatic beta cells to palmitate is dependent on the presence of a stimulatory glucose concentration.

Long-term exposure of pancreatic beta cells to elevated levels of fatty acids (FAs) impairs glucose-induced insulin secretion. However, the effects of FAs on insulin gene expression are controversial. We hypothesized that FAs adversely affect insulin gene expression only in the presence of elevated glucose concentrations. To test this hypothesis, isolated rat islets were cultured for up to 1 week in the presence of 2.8 or 16.7 mmol/L glucose with or without 0.5 mmol/L palmitate. Insulin release, insulin content, and insulin mRNA levels were determined at the end of each culture period. Palmitate increased insulin release at each time point independently of the glucose concentration. In contrast, insulin content was unchanged in the presence of palmitate at 2.8 mmol/L glucose, but was markedly decreased in the presence of 0.5 mmol/L palmitate and 16.7 mmol/L glucose after 2, 3, and 7 days of culture. In the presence of a basal concentration of glucose, insulin mRNA levels were transiently increased by palmitate at 24 hours but were unchanged thereafter. In contrast, palmitate significantly inhibited the stimulatory effects of 16.7 mmol/L glucose on insulin mRNA levels after 2, 3, and 7 days. To determine whether the inhibitory effect of palmitate on glucose-stimulated insulin mRNA levels was associated with decreased insulin promoter activity, HIT-T15 cells were cultured for 24 hours in 11.1 mmol/L glucose in the presence or absence of palmitate, and insulin gene promoter activity was measured in transient transfection experiments using the insulin promoter-reporter construct INSLUC. INSLUC activity was decreased more than 2-fold after 24 hours of exposure to 0.5 mmol/L palmitate. We conclude that long-term exposure of pancreatic beta cells to palmitate decreases insulin gene expression only in the presence of elevated glucose concentrations, in part through inhibition of insulin gene promoter activity.

Outcome of severe diabetic foot ulcers after standardised management in a specialised unit.

OBJECTIVE: The primary objective was to evaluate the efficacy in terms of limb salvage and healing time of standardised multidisciplinary management for high-grade diabetic foot ulcers. The secondary objective was to retrospectively identify the factors that influenced time to healing. STUDY DESIGN AND METHODS: Over a 2-year period, 157 patients with diabetic foot ulcers were managed in our specialised unit using a standard treatment strategy; 118 were followed until healing or for at least 7 months (range, 7-29) after hospital discharge and form the basis for this study. Predetermined criteria were used to diagnose and manage the lesions. The number of major amputations and the time to healing were the main outcome measures. Univariable and multivariable analyses were done retrospectively to look for factors associated with time to healing. RESULTS: The limb salvage rate was 97.5% and the healing rate was 50% after 10 months and 70% after 16 months. Factors significantly associated with healing time were arterial disease without bypass surgery (p<0.001) and renal replacement therapy (p<0.05). Osteomyelitis, as managed in this study, did not increase the healing time (p > 0.6). CONCLUSION: In high-grade diabetic foot ulcers, standardised conservative management with second-line bone-sparing surgery, if needed, yields an acceptable limb salvage rate. With combined medical and surgical treatment, osteomyelitis is not a poor prognosis factor.

[Role and modalities of insulin treatment in type 2 diabetics]. / Place et modalités de l'insulinothérapie chez le diabétique de type 2.

INTRODUCTION: The natural history of type 2 diabetes mellitus is characterized by an inescapable and gradual worsening of a decrease in insulin secretion. Thus after several years of progress, less than half of type 2 diabetic patients have good glycemic control. This explains the increase in insulin prescription to type 2 diabetic patients in France in recent years. This work's objective is to take into account recent publication data to clarify the status of and adjustments in insulin therapy. CURRENT KNOWLEDGE AND KEY POINTS: The benefit of insulin treatment-mediated glycemic control optimization on microvascular complications is now proven. However, there is still controversy concerning macrovascular complications. Hypoglycemic risk in type 2 diabetic patients is limited and the main problem with insulin treatment is weight gain. Following failure with treatment by tablets, the most suitable treatment in terms of metabolic improvement, weight gain limitation and treatment adhesion is to add an intermediate insulin injection at bedtime. The next step remains several injections a day, with metformine addition if possible. FUTURE PROSPECTS AND PROJECTS: Therapeutic treatment in type 2 diabetes mellitus may become an earlier start of insulin therapy to preserve the remaining pancreatic insulin reserve. The role of brief and long-lasting insulin analogues, as well as inhaled insulin, which will soon be available, should be specified.

[Adrenal histoplasmosis in a non-insulin-dependent diabetic patient]. / Histoplasmose surrénalienne chez un sujet idabétique non insulinodépendant.

Adrenal histoplasmosis is a rare infection that can be misdiagnosed as tuberculosis. We present here a case of adrenal histoplasmosis in a 65 year-old male diabetic with marked weight loss. Laboratory investigations noticed an inflammatory syndrome and the abdominal computed tomography scanner reported an heterogenous left adrenal mass of 6 cm in diameter. Hormonal as well as bacteriological studies were negative. The patient was operated and the histopathological examination proved that the mass was a tuberculoma and an anti-tuberculous treatment was started. Four months later, the patient suffered from recurrence of symptoms and laboratory investigations confirmed the inflammatory syndrome and the abdominal computed tomography scanner showed a right adrenal mass. A surgical biopsy was performed and specific fungal researches proved that the lesion was due to Histoplasma capsulatum. The patient experienced a remarkable improvement under anti-fungal treatment.

Prognostic value of liver fibrosis and steatosis biomarkers in type-2 diabetes and dyslipidaemia.

BACKGROUND: In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. AIM: To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. METHODS: A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5-15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. RESULTS: During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [HR (95% CI)] [2.98 (95% CI 1.78-4.99); P < 0.0001] or severe steatosis [1.86 (1.34-2.58); P = 0.0002] was associated with an increased risk of mortality. In a multivariate Cox model adjusted for confounders: the presence of advanced fibrosis was associated with overall mortality [1.95 (1.12-3.41); P = 0.02]; advanced fibrosis at baseline [n = 50/677; 1.92 (1.04-3.55); P = 0.04] and progression to advanced fibrosis during follow-up [n = 16/127; 4.8 (1.5-14.9); P = 0.007] were predictors of cardiovascular events in patients with type-2 diabetes. In patients with a Framingham-risk score ≥20%, the presence of advanced fibrosis was predictive of cardiovascular events [2.24 (1.16-4.33); P < 0.05]. CONCLUSIONS: Liver biomarkers, such as FibroTest and SteatoTest, have prognostic values in patients with metabolic disorders. FibroTest has prognostic value for predicting overall survival in patients with type-2 diabetes and/or dyslipidaemia. In type-2 diabetes, FibroTest predicted cardiovascular events and improved the Framingham-risk score.

[Chronic maternal diseases and pregnancy losses. French guidelines]. / Pathologies maternelles chroniques et pertes de grossesse. Recommandations françaises.

AIM: To review the available data on maternal chronic diseases and pregnancy losses. MATERIAL AND METHODS: We searched PubMed and the Cochrane library with pregnancy loss, stillbirth, intrauterine fetal demise, intrauterine fetal death, miscarriage and each maternal diseases of this paper. RESULTS: Antiphospholipid antibodies (anticardiolipin, anti-beta-2-glycoprotein, lupus anticoagulant) should be measured in case of miscarriage after 10WG confirmed by ultrasound (grade B) and an antiphospholipid syndrome should be treated by a combination of aspirin and low-molecular-weight heparin during a subsequent pregnancy (grade A). We do not recommend testing for genetic thrombophilia in case of first trimester miscarriage (grade B) or stillbirth (grade C). Glycemic control should be a goal before pregnancy for women with pregestational diabetes to limit the risks of pregnancy loss (grade A) with a goal of prepregnancy HbA1c<7%. Overt and subclinical hypothyroidisms should be treated by L-thyroxin during pregnancy to reduce the risks of pregnancy loss (grade A). Women who are positive for TPOAb should have TSH concentrations follow-up during pregnancy and subsequently treated by L-thyroxin if they develop subclinical hypothyroidism (grade B). CONCLUSIONS: Prepregnancy management of most chronic maternal diseases, ideally through prepregnancy multidisciplinary counseling, reduces the risks of pregnancy loss.

[Management of gestational diabetes]. / Prise en charge thérapeutique du diabète gestationnel.

BACKGROUND: Maternal and perinatal complications linked to gestational diabetes could be decreased with an intensive treatment. AIM: To assess the effect of various treatments, glycaemia targets and procedures for blood glucose self-monitoring, on fetal and maternal prognosis. METHODS: Systematic review of literature studying the efficacy of the treatment of gestational diabetes to decrease fetal morbi-mortality thereof. Analysis based on bibliographic search in pubmed using the following keywords: "therapeutic", "treatment" and "gestational diabetes". RESULTS: Specific treatment of gestational diabetes (dietetics, physical exercise, blood glucose self-monitoring, insulin-therapy if appropriate) reduces severe perinatal complications (composite criterion), fetal macrosomia and pre-eclampsia compared to the absence of therapy, with however an increase in the number of triggered deliveries, and without any increase in the number of cesarean sections. Regarding oral antidiabetics, despite no difference was found in fetal or maternal prognosis upon treatment with glyburide, metformin, or insulin, they should not be prescribed. CONCLUSION: The treatment of "severe or moderate" gestational diabetes is recommended. Additional studies, in particular long-term studies in children, are warranted before oral antidiabetics can be used.

Therapeutic management of gestational diabetes.

BACKGROUND: Maternal and perinatal complications linked to gestational diabetes mellitus could be decreased with an intensive management approach. AIM: To assess the effect of various treatments, glycaemic targets and procedures for self-monitoring of blood glucose on the foetal and maternal prognosis. METHODS: Systematic review of literature studying the efficacy of the treatment of gestational diabetes in order to decrease maternal-foetal morbidity-mortality. Analysis based on bibliographic search in PubMed using the following keywords: "therapeutic", "treatment" and "gestational diabetes". RESULTS: Specific treatment of gestational diabetes (dietary, adapted physical activity, self-monitoring of blood glucose, insulin-therapy if appropriate) reduces severe perinatal complications (composite criterion), foetal macrosomia and preeclampsia compared to the absence of therapy, with however an increase in the number of labour inductions, and without any increase in the number of caesarean sections. Regarding oral antidiabetic agents (glibenclamide or metformin), despite the absence of difference found on foetal or maternal prognosis compared to insulin, they should not be prescribed during pregnancy at this time. CONCLUSION: The treatment of "severe or moderate" gestational diabetes is recommended. Additional studies, in particular long-term studies in children, are warranted before oral antidiabetic agents can be used.

Use of insulin glargine throughout pregnancy in 102 women with type 1 diabetes.

AIM: The aim of this study was to examine the safety of insulin glargine during pregnancy in women with type 1 diabetes mellitus (T1DM). METHODS: This retrospective multicentre study involved women with T1DM treated with insulin glargine before conception and throughout pregnancy. The main investigated parameters were HbA(1c) during the first and third trimesters, major congenital malformations, and perinatal mortality and complications. RESULTS: For the 102 women with T1DM in the study, HbA(1c) during the first and third trimesters was 6.7+/-1.2% (95% CI 6.4-6.9%) and 6.2+/-0.9% (95% CI 6.0-6.4%), respectively. Two congenital malformations (2%) were reported, and one stillbirth (1%) occurred at week 35 of gestation. The rate of preterm delivery was 23%. The mean birth weight was 3381+/-595 g (95% CI 3255-3506 g), and the proportion of large-for-gestational-age infants was 30%. CONCLUSION: Insulin glargine use throughout pregnancy does not appear to be associated with an increased rate of severe congenital malformations.