Empagliflozin influences blood viscosity and wall shear stress in subjects with type 2 diabetes mellitus compared with incretin-based therapy.

BACKGROUND: Cardiovascular protection following empagliflozin therapy is not entirely attributable to the glucose lowering effect. Increased hematocrit might influence the shear stress that is the main force acting on the endothelium, regulating its anti-atherogenic function. OBJECTIVE: We designed the study with the aim of investigating the effect of empagliflozin on blood viscosity and shear stress in the carotid arteries. A secondary endpoint was the effect of empagliflozin on carotid artery wall thickness. METHODS: The study was a non-randomized, open, prospective cohort study including 35 type 2 diabetic outpatients who were offered empagliflozin or incretin-based therapy (7 liraglutide, 8 sitagliptin) in combination with insulin and metformin. Blood viscosity, shear stress and carotid wall thickness were measured at baseline and at 1 and 3 months of treatment. Blood viscosity was measured with a viscometer, and shear stress was calculated using a validated formula. Intima-media thickness (IMT) of the carotid artery was detected by ultrasound and was measured with dedicated software. RESULTS: Blood viscosity (4.87 ± 0.57 vs 5.32 ± 0.66 cP, p < 0.02) and shear stress significantly increased in the Empagliflozin group while no change was detected in the Control group (4.66 ± 0.56 vs 4.98 ± 0.73 cP, p = NS). IMT significantly decreased in the Empagliflozin group after 1 and 3 months (baseline: 831 ± 156, 1-month 793 ± 150, 3-month 766 ± 127 µm; p < 0.0001), while in the liraglutide group, IMT significantly decreased only after 3 months (baseline 879 ± 120; 1-month 861 ± 163; 3-month 802 ± 114 µm; p < 0.001). In the sitagliptin group, IMT remained almost unchanged (baseline 901 ± 135; 1-month 902 ± 129; 3-month 880 ± 140 µm; p = NS). CONCLUSIONS: This study is the first to describe a direct effect of empagliflozin on blood viscosity and wall shear stress. Furthermore, IMT was markedly reduced early on in the Empagliflozin group.

Impact of Seasonality on Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a major health concern that seems to be influenced by seasonality. OBJECTIVE: To assess the impact of seasonality on the incidence of GDM in an Italian population. METHOD: This is a retrospective cohort study of 5,473 pregnant women attending the Operative Unit of Diabetes, who underwent GDM screening by means of the 75-g oral glucose tolerance test (OGTT), during the period from August 2011 to December 2016. Screening was performed at 16-18 or 24-28 weeks&apos; gestation, following the Health Italian Minister guidelines. All blood samples were undertaken in the Hospital itself, under the same temperature conditions, and analyzed in the nearby biochemical laboratory. Statistical analysis was performed by SPSS software. RESULTS: 1,559 of 5,473 enrolled women (28.5%) were affected by GDM. The incidence of GDM was significantly higher during the summer season (33.7%) (P<0.001), and significantly lower during the winter (23.3%), compared with spring (P=0.035) and fall seasons (P=0.002). When the year was divided on a 24-hr temperature basis into two parts only, the warm half and the cold half, GDM was considerably lower in cold months compared to warm ones (P<0.0001). No difference was observed between the medians of fasting glycemia throughout the four seasons; instead, serum glucose levels at 1-h and 2-h after OGTT were higher in summer than in spring, autumn and winter. Results from multiple linear regression analysis supported the hypothesis that glucose levels at 1-h and 2-h following OGTT could be influenced by ambient temperature. CONCLUSION: Our data indicate that seasonal changes may influence variations in glucose tolerance during pregnancy, with GDM incidence increasing during the summer and declining during cold months.

A new predictive tool for the early risk assessment of gestational diabetes mellitus.

AIMS: The Italian National Institute of Health has recently introduced a selective screening based on the risk profile of pregnant women, which while recommending against screening of women at low risk (LR) for GDM, it recommends an early test for women at high risk (HR) for GDM. Herein, we assessed the accuracy and cost-effectiveness of this screening and developed a new index that improves these requirements. METHODS: We retrospectively enrolled 3974 pregnant women. GDM was diagnosed with a 2h 75-g OGTT at 16-18 weeks (early test) or 24-28 weeks of gestation, according to the IADPSG guidelines. RESULTS: 55.6% of HR women had GDM, although only 38.4% underwent early screening. Among 2654 women at medium risk, 20.9% had GDM; paradoxically, among 770 LR women, that would not have been screened, 26.6% received a GDM diagnosis. Based on these unsatisfactory results, we elaborated the Capula's index, that reduced both screening tests (p<0.001) and potentially undetected GDM cases (p<0.001), and corrected the paradoxical prevalence estimates of GDM obtained with the current Italian guidelines. Also, Capula's index improved correlation of GDM risk profile with obstetric and neonatal adverse events. CONCLUSIONS: Capula's index improves accuracy of selective screening for GDM.

Add-On Treatment with Liraglutide Improves Glycemic Control in Patients with Type 2 Diabetes on Metformin Therapy.

BACKGROUND: Liraglutide is a glucagon-like peptide-1 receptor analog recently approved for the treatment of type 2 diabetes mellitus (T2DM). We aimed to assess the efficacy and safety of liraglutide versus glimepiride, as adjunct treatments to metformin, in achieving glycemic control in Italian patients with T2DM uncontrolled by metformin alone. SUBJECTS AND METHODS: One hundred seventy-nine diabetes patients treated with metformin plus liraglutide (1.8 mg) or glimepiride (4 mg) were retrospectively assessed at baseline, during, and after 18 months of continuous therapy. RESULTS: Treatment with liraglutide resulted in mean decreases in hemoglobin A1c (HbA1c) of -1.4%, when compared with glimepiride (-0.4%) (P < 0.001), and was followed by a significant reduction (P < 0.001) in fasting plasma glucose. Variations in HbA1c occurred independently from weight loss, which was significantly reduced (P < 0.001) in liraglutide-treated patients. The percentage of subjects reaching HbA1c levels below 7% or ≤ 6.5% was significantly different between the two treated groups (P < 0.001). Treatment with liraglutide reduced waist circumference (WC) (P < 0.001) and decreased both systolic and diastolic blood pressure (BP) (P < 0.001). It is interesting that the study also showed the impact of female gender in predicting a better glycemic response to liraglutide (P = 0.028). CONCLUSIONS: Liraglutide was more effective than glimepiride in reducing HbA1c levels in treated patients with T2DM. This was evident in both genders, but particularly in women. Furthermore, liraglutide reduced body weight, WC, and BP, which are critical risk factors for cardiovascular disease.

Clinical evolution of autoimmune thyroiditis in children and adolescents.

BACKGROUND: Few studies have addressed the clinical evolution of autoimmune thyroiditis (AIT) occurring in childhood and scant data are available on the role of thyroid ultrasonography. We aimed to evaluate the natural history of AIT diagnosed in children and adolescents and to assess the possible prognostic role of ultrasonography. METHODS: Retrospective case series prospectively followed up for a further 3-year period. RESULTS: A series of 23 patients with AIT, diagnosed before 18 years of age from 1994 to 2004, was further followed up from 2005 to 2007 with clinical, laboratory, and ultrasound evaluation. Hypothyroid patients were treated with levothyroxine (LT(4)), while euthyroid patients were left untreated. Patients with subclinical hypothyroidism were also evaluated 40 days after LT(4) withdrawal. At diagnosis seven patients were euthyroid, 14 with subclinical hypothyroidism, and two with overt hypothyroidism. Median follow-up was 4.7 years. At last follow-up visit, none of the seven euthyroid patients had developed hypothyroidism. Three of the 14 patients with subclinical hypothyroidism recovered a normal thyroid function while only one patient showed an increase in TSH level. By serological screening we identified three patients with other autoimmune disorders. CONCLUSIONS: In young patients with normal or mildly increased TSH levels and minimal echographic changes, AIT may remain stationary for years. In fact, patients with subclinical hypothyroidism recover a normal thyroid function in approximately 20% of cases. In patients with subclinical hypothyroidism and goiter, LT(4) therapy may induce thyroid size reduction. Screening for other autoimmune disorders is useful to identify patients that need further diagnostic assessment.