Postpartum screening for type 2 diabetes mellitus in women with gestational diabetes: Is it really performed?

AIMS: This study evaluates the adherence to postpartum type 2 diabetes mellitus (T2DM) screening in women with previous gestational diabetes (GDM) and identifies elements associated with poor attendance. METHODS: We retrospectively collected data from 650 consecutive women with GDM between 2016 and 2018, who should had 75 g-OGTT, 4-12 weeks after delivery. Impaired glucose regulation (IGR) was defined according with ADA criteria. RESULTS: Only 41% of women had postpartum OGTT. Of these, 1.9% received T2DM diagnosis, with IGR prevalence of 18%. After introducing a recommendation letter, adherence to screening increased (47% in 2017 and 43% in 2018 vs. 32% in 2016). Screening procedure was less common in women with: no-family history of T2DM (38% vs. 46%; p < 0.05), age <35 (33% vs. 47%; p < 0.01), lower level of education (32% no-high-school-diploma vs. 35% high-school-diploma vs. 49% university-degree; p < 0.01) and unstable employment (35% vs. 44%; p < 0.05). At multivariate logistic regression analysis, age <35 years (OR 1.61; 95%CI: 1.14-2.28) and lowest educational level (OR 1.64; 95% CI: 1.13-2.37, compared to University degree) were independently associated with non-adherence. CONCLUSION: Only 41% of women had postpartum T2DM screening. Women with lower attendance are those with age <35 years or low educational level. Further strategies are needed to implement postpartum test.

The use of real time continuous glucose monitoring or flash glucose monitoring in the management of diabetes: A consensus view of Italian diabetes experts using the Delphi method.

Until recently, in Italy, the use of continuous glucose monitoring (CGM) systems has been limited, but is now rapidly increasing, including the so-called real-time CGM (rtCGM) and the intermittently viewed CGM (iCGM), also called Flash Glucose Monitoring (FGM). These technologies overcome many of the limitations of self-monitoring of blood glucose (SMBG) by fingerprick and allow to go beyond HbA1c to check glucose control in diabetes. However, standardized protocols for applying and interpreting rtCGM and FGM data are lacking. In this paper, we delineate a consensus amongst Italian diabetes physicians on the attributes of rtCGM and FGM technologies, and introduce a consistent approach for their use by Italian healthcare professionals. Most experts consider rtCGM and FGM as two separate categories of interstitial subcutaneous fluid (ISF) sensing technologies, and see them as superior to SMBG. Furthermore, there is strong consensus that rtCGM and FGM reduce hypoglycemia risk, increase the amount of time in the target glucose range and augment treatment satisfaction. However, there is still no agreement on the indication of the FGM for subjects who suffer asymptomatic hypoglycemia. Consensus on the role of education in initiating and optimizing use of rtCGM/FGM and about the interpretation of glucose trends was near unanimous, whereas no consensus was reached on the statement that there are no disadvantages/risks of rtCGM/FGM. Some issues remain in rtCGM/FGM management: a) risk of excessive correction of high or low glucose; b) risk of alert fatigue leading to alert silencing or rtCGM termination; c) allergic reaction to the adhesive keeping rtCGM or FGM sensors in place. The panel almost unanimously agreed that sensor accuracy depends on multiple variables, that alarm setting should be individualized, and that global glycemic profile represent an useful tool in interpreting glucose data. More clinical studies and a wider use of these devices will increase the efficacy and effectiveness of continuous glucose monitoring in Italy.

Early vs. standard screening and treatment of gestational diabetes in high-risk women - An attempt to determine relative advantages and disadvantages.

BACKGROUND AND AIMS: Screening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16-18 weeks) and treatment of GDM may improve maternal and fetal outcomes. METHODS AND RESULTS: In 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). CONCLUSION: Early vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.

The role of adipokines in the pathogenesis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.

Factors influencing safe glucose-lowering in older adults with type 2 diabetes: A PeRsOn-centred ApproaCh To IndiVidualisEd (PROACTIVE) Glycemic Goals for older people: A position statement of Primary Care Diabetes Europe.

Diabetes in later life is associated with a range of factors increasing the complexity of glycaemic management. This position statement, developed from an extensive literature review of the subject area, represents a consensus opinion of primary care clinicians and diabetes specialists. It highlights many challenges facing older people living with type 2 diabetes and aims to support primary care clinicians in advocating a comprehensive, holistic approach. It emphasises the importance of the wishes of the individual and their carers when determining glycaemic goals, as well as the need to balance intended benefits of treatment against the risk of adverse treatment effects. Its ultimate aim is to promote consistent high-quality care for older people with diabetes.

Baseline characteristics in the VERIFY study: a randomized trial assessing the durability of glycaemic control with early vildagliptin-metformin combination in newly diagnosed Type 2 diabetes.

AIM: To assess the long-term clinical benefits of early combination treatment with vildagliptin-metformin vs. standard-of-care, metformin monotherapy in the ongoing VERIFY study. METHODS: We randomized 2001 participants with multi-ethnic background, aged 18-70 years, having HbA1c levels 48-58 mmol/mol (6.5-7.5%) and BMI 22-40 kg/m2 . Baseline data included HbA1c , fasting plasma glucose and homeostasis model ß-cell and insulin sensitivity. Standardized meal-tests, insulin secretion rate relative to glucose, and oral glucose insulin sensitivity were assessed in a subpopulation. RESULTS: Out of 4524 screened, data were collected from the 2001 eligible participants (53% women) across Europe (52.4%), Latin America (26.8%), Asia (17.2%), South Africa (3.1%) and Australia (0.5%). The median (interquartile range) disease duration was 3.4 (0.9, 10.2) months; mean (±SD) age 54.3±9.4 years; weight 85.5±17.5 kg and BMI 31.1±4.7 kg/m2 . Baseline HbA1c was 52±3 mmol/mol (6.9±0.3%), fasting plasma glucose 7.5±1.5 mmol/l and the median (interquartile range) of fasting insulin was 109 (75-160) mU/l. Homeostasis model ß-cell and insulin sensitivity values were 84% (60, 116) and 46% (31, 68), respectively. In those undertaking meal-tests, insulin secretion rate relative to glucose was 28±12 pmol/min/m2 /mmol/l and oral glucose insulin sensitivity was 353±57 ml/min/m2 . CONCLUSIONS: Our current, multi-ethnic, newly diagnosed VERIFY population reflects a characteristic presence of early insulin resistance in participants with increased demand for insulin associated with obesity. The VERIFY study will provide unique evidence in characterizing therapeutic intervention in a diverse population with hyperglycaemia, focusing on durability of early glycaemic control.

Italian national guidelines for the screening of gestational diabetes: Time for a critical appraisal?

BACKGROUND AND AIM: In 2011, the Italian National Health System guidelines introduced a selective screening for gestational diabetes (GDM) based on risk factors, recommending early evaluation in high risk women. The present study examined to which extent guidelines are applied, and analyzed the effectiveness of GDM diagnosis according to risk profile. METHODS AND RESULTS: We analyzed 1338 pregnant women, consecutively screened for GDM with a 75 g OGTT between January 2013 and December 2015, according to national guidelines. Diagnosis of GDM was based on IADPSG/WHO 2013 criteria. As many as 14.4% of screened women was at high risk, 64% at medium, 21.6% did not have any risk factor. Only 50% of high-risk women were appropriately screened at 16th-18th gestational weeks; 28% of them repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in high risk women (67% vs. 40% medium risk vs. 22% low risk; p < 0.0001). An early GDM diagnosis was performed in 40.7% of high-risk women. In low risk women, gestational weight gain at the screening time was independently associated with GDM. CONCLUSIONS: The recommendations for the screening of GDM are still insufficiently implemented, especially for early evaluation in high risk women. Considering the high proportion of early GDM diagnosis, the poor adherence to screening recommendation may result in late diagnosis of GDM. Finally, our finding of a 22% prevalence of GDM among low risk women suggests the need to consider additional risk factors, such as excessive weight gain during pregnancy.

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus.

INTRODUCTION: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin . Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM-INSULIN trial.

AIMS: The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. METHODS: ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. RESULTS: This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. CONCLUSION: The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.

Efficacy and safety of linagliptin according to patient baseline characteristics: A pooled analysis of three phase 3 trials.

BACKGROUND AND AIMS: We aimed to determine if patient baseline characteristics affect responses to linagliptin and identify relevant predictors of glycated hemoglobin (HbA1c) reduction in patients with type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: Data were pooled from three 24-week, placebo-controlled trials of similar design (linagliptin, n = 1651; placebo, n = 607). Patients were categorized according to baseline characteristics: age, T2DM duration, gender, body mass index (BMI), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and metabolic syndrome (MetS). Changes from baseline in HbA1c after 24 weeks were assessed with analysis of covariance (ANCOVA). The proportion of patients with baseline HbA1c >7% achieving HbA1c of ≤7% at week 24 were evaluated. Independent predictors of HbA1c response with linagliptin were analyzed in a multivariate analysis with ANCOVA. Linagliptin treatment led to significant mean (SE) placebo-corrected reductions from baseline in HbA1c across all subgroups (-0.42% [±0.11] to -0.79% [0.08]; all p < 0.001). Within subgroups, HbA1c reduction was more pronounced in patients without MetS (-0.74% [0.06]; treatment interaction p = 0.0489). The proportion of patients with baseline HbA1c >7% achieving a target HbA1c ≤7% was greater with linagliptin versus placebo (30.2% vs 11.5%; odds ratio 3.82; 95% CI 2.82 to 5.17; p < 0.001). Characteristics significantly predicting HbA1c reductions after 24 weeks were fasting plasma glucose and race (both p < 0.05). CONCLUSION: This post-hoc analysis supports that linagliptin achieved clinically meaningful improvements in hyperglycemia in patients with diverse clinical characteristics. These improvements were more pronounced in patients without MetS.