Time in Range Analysis in Automated Insulin Delivery Era: Should Day and Nighttime Targets be the Same?

INTRODUCTION: Hybrid closed-loop systems (HCLS) use has shown that time in range (TIR) tends to improve more during the nighttime than during the day. This study aims to compare the conventional TIR, currently accepted as 70 to 180 mg/dL, with a proposed recalculated time in range (RTIR) considering a tighter glucose target of 70 to 140 mg/dL for the nighttime fasting period in T1DM patients under HCLS. METHODS: We conducted a retrospective study that included adults patients receiving treatment with Tandem t:slim X2 Control-IQ. Daytime TIR was characterized as glucose values between 70 and 180 mg/dL during the 07:01 to 23:59 time frame. Nighttime fasting TIR was specified as glucose values from 70 to 140 mg/dL between 00:00 and 07:00. The combination of the daytime and nighttime fasting glucose targets results in an RTIR, which was compared with the conventional TIR for each patient. The 14 days Dexcom G6 CGM data were downloaded from Tidepool platform and analyzed. RESULTS: We included 22 patients with a mean age of 49.7 years and diabetes duration of 24.7 years, who had been using automatic insulin delivery (AID) HCLS for a median of 305.3 days. We verified a mean conventional TIR of 68.7% vs a mean RTIR of 60.3%, with a mean percentage difference between these two metrics of -8.4%. A significant decrease in conventional TIR was verified when tighter glucose targets were considered during the nighttime period. No significant correlation was found between the percentage difference values and RTIR, even among the group of patients with the lowest conventional TIR. CONCLUSIONS: Currently, meeting the conventional TIR metrics may fall short of achieving an ideal level of glycemic control. An individualized strategy should be adopted until further data become available for a precise definition of optimal glucose targets.

Efficacy and safety of SGLT2 inhibitors in individuals with type 1 diabetes under continuous subcutaneous insulin infusion: a real-world study.

Objective. Adjuvant therapy with sodium-glucose cotransport 2 inhibitors (SGLT2i) in type 1 diabetes (T1D) is associated with an improvement in glycemic control, but increases the risk of diabetic ketoacidosis (DKA). However, real-life studies in individuals with T1D under continuous subcutaneous insulin infusion (CSII) are still scarce. We present the first real-life study performed in patients with T1D exclusively treated with CSII. The aim of the present study was to assess the metabolic impact and safety of SGLT2i in T1D individuals under CSII. Methods. Retrospective study includes 34 T1D adult individuals under CSII, who started SGLT2i until 30th June 2021. Data regarding the glycemic control and acute diabetes complications at the moment of introduction of SGLT2i and after 3, 6, and 12 months of use were collected. Results. Twenty-three individuals were included. Comparing with the moment of SGLT2i introduction after 3, 6, and 12 months of use, there was a statistically significant increase of time in range (TIR) (∆T3M=12.8%; ∆T6M=11.5%; ∆T12M=11.1%), and a decrease in time above range (∆T3M=13.6%; ∆T6M=11.9%; ∆T12M=10.5%). There were no significant differences in time below the range. Mean glucose and mean glucose management indicator significantly reduced in the 3 evaluated moments. A significant reduction in median weight was also observed (∆T6M=2 kg; ∆T12M=4.5 kg). Two patients (8.7%) developed mild euglycemic DKA during SGLT2i treatment, both were women and had body mass index (BMI) <27 kg/m2. One of them had a total daily insulin dose (TDDI) reduction of 26.9% after 3 months of use. Conclusions. The use of SGLT2i, as an adjuvant treatment in T1D individuals under CSII, was associated with a significant increase of TIR without increasing time in hypoglycemia. It also had a weight benefit. Careful use in selected participants is necessary to reduce the occurrence of DKA.

Inappropriate gestational weight gain impact on maternofetal outcomes in gestational diabetes.

OBJECTIVE: To evaluate the association between the dimension of deviation from appropriate gestational weight gain (GWG) and adverse maternofetal outcomes in women with gestational diabetes mellitus (GDM). METHODS: We performed a multicentric retrospective study based on the Portuguese GDM Database. Women were classified as within GWG, insufficient (IGWG) or excessive (EGWG) than the Institute of Medicine recommendations. EGWG and IGWG were calculated for each prepregnancy BMI category. Large-for-gestational-age (LGA) and macrosomia were defined as a birthweight more than the 90th percentile for the gestational age and newborn weight greater than 4000 g, respectively. Logistic regression models (adjusted odds ratio [aOR] plus 95% confidence interval [95%CI]) were derived to evaluate the association between EGWG or IGWG and adverse maternofetal outcomes. RESULTS: A total of 18961 pregnant women were included: 39.7% with IGWG and 27.8% with EGWG. An EGWG over 3 kg was associated with a higher risk of LGA infants (aOR 1.95, 95%CI 1.17-3.26) and macrosomia (aOR 2.01, 95%CI 1.23-3.27) in prepregnancy normal weight women. An EGWG greater than 4 kg was associated with a higher risk of LGA infants (aOR 1.67, 95%CI 1.23-2.23) and macrosomia (aOR 1.90, 95%CI 1.38-2.61) in obese women. In overweight women, an EGWG above 3.5 kg was associated with a higher risk of LGA infants (aOR 1.65, 95%CI 1.16-2.34), macrosomia (aOR 1.85, 95%CI 1.30-2.64), preeclampsia (aOR 2.40, 95%CI 1.45-3.98) and pregnancy-induced hypertension (aOR 2.21, 95%CI 1.52-3.21). An IGWG below -3.1 kg or -3kg was associated with a higher risk of small-for-gestational-age [SGA] infants in women with normal (OR 1.40, 95%CI 1.03-1.90) and underweight (OR 2.29, 95%CI 1.09-4.80), respectively. CONCLUSIONS: Inappropriate gestational weight gain seems to be associated with an increased risk for adverse maternofetal outcomes, regardless of prepregnancy BMI. Beyond glycemic control, weight management in women with GDM must be a focus of special attention to prevent adverse pregnancy outcomes.KEY MESSAGESThe dimension of deviation from appropriate gestational weight gain was associated with an increased risk for adverse maternofetal outcomes among women with gestational diabetes.Weight management must be a focus of special attention in women with gestational diabetes to prevent adverse pregnancy outcomes.

Faster Insulin Aspart for Continuous Subcutaneous Insulin Infusion: Is It Worth It?

Introduction Faster insulin aspart (fASP) is the new formulation of insulin aspart (ASP) with a left-shifted pharmacokinetic profile, allowing better control of early postprandial hyperglycemia and a reduction in the risk of late post-meal hypoglycemia. However, it can be associated with more frequent infusion set changes. The purpose of this study is to evaluate efficacy and safety one, three, and six months after starting fASP in continuous subcutaneous insulin infusion (CSII) systems. Methods This is a retrospective study that included adults with type 1 diabetes mellitus, users of CSII ≥3 months, who started fASP. Exclusion criteria included less than one month of follow-up after the intervention, concomitant initiation of pharmacological therapy, pre-conception period, and non-use of continuous glucose monitoring. Results A total of 77 individuals were included, of which 52 (67.5%) were female, aged 39.87 ± 13.10 years, with a mean time under CSII of 7.30 ± 3.58 years and a median follow-up time after transition to fASP of six months. There was a trend to a global glycemic control improvement at six months after starting fASP: numeric increase in time in range (56.40 ± 12.62% vs 60.15 ± 13.53%, p=0.148), reduction in time above range (37.76 ± 13.05% vs 34.67 ± 14.94%, p=0.557), time below range (6.00 (5.00)% vs 4.50 (5.25)%, p=0.122), and mean glucose (174.29 ± 25.14 mg/dL vs 167.00 ± 25.30 mg/dL, p=0.207). There was a reduction in body mass index (BMI) at six months after switching to fASP (25.08 (4.59) kg/m2 vs 24.45 (3.05) kg/m2, p=0.010), despite the absence of a significant variation in total daily insulin. Adverse event and discontinuation rates were 7.8% and 6.5%, respectively, with no documented episodes of diabetic ketoacidosis or severe hypoglycemia. Conclusions fASP proved to be a safe and effective therapeutic option in CSII systems associated with a significant BMI reduction, aspects that might justify its preference.

Predictors of metformin monotherapy failure in gestational diabetes mellitus.

Objective: Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence. Design and methods: This was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed. Results: In 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008-1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028-1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796-0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks. Conclusions: In 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.

Impact of intermittently scanned continuous glucose monitoring on quality of life and glycaemic control in persons with type 1 diabetes: A 12-month follow-up study in real life.

BACKGROUND AND AIM: We sought to prospectively assess the impact of intermittently scanned continuous glucose monitoring (isCGM) initiation in the glycaemic control and quality of life (QoL) in type 1 diabetes mellitus (T1DM) patients followed in real-live conditions. METHODS: Prospective, observational, cohort, single-centre and single-arm study conducted between September 2018 and March 2020, enrolling adults with T1DM with at least one year of diagnosis, interested in using isCGM. After training at isCGM initiation, CGM metrics and QoL were assessed at baseline and 12 months. RESULTS: Thirty-six individuals (55.6% male) were included; median age at inclusion was 49.0 (43.5-62.5)years and the mean(±SD) duration of T1DM was 25.5 ± 12.0 years. Median (interquartile range) HbA1c decreased from 7.6(7.0-8.7)% to 7.4(6.8-7.7)% at 12 months (p = 0.02), driven by the subgroup of individuals with baseline HbA1c ≥ 7.5%. The number of scans per day increased from 7.0(5.5-10.0) to 10.0(7.0-14.0) but no correlation was found between the number of daily scans and CGM metrics. Total daily insulin dose remained unchanged, however the proportion of basal insulin decreased, and the proportion of bolus insulin increased over time. Multiple QoL subscales scores improved significantly, including disease-burden subscale for which TIR proved to be a significant predictive factor. CONCLUSION: isCGM improved both glycaemic control, namely time in range, time below range and glycaemic variability, as well as QoL scores in the long term. The increase of the bolus insulin proportion suggests a behavioural change. However, the appraisal of our results must consider our substantial rate of drop-out limiting the external validity of our findings.

Severe Hyperthyroidism and Complete Hydatidiform Mole in Perimenopausal Woman: Case Report and Literature Review.

Gestational trophoblastic disease (GTD) represents a heterogeneous group of disorders within placental trophoblastic cells that are rather rare in perimenopausal ages. One of its complications is the development of secondary clinical hyperthyroidism, which can be potentially complicated if not properly and early recognized. We report the case of a 50-year-old perimenopausal woman, gravida 2 para 2, who presented to the emergency department with severe acute lower abdominal pain and abnormal uterine bleeding for one month. She also reported abnormal sweating and palpitation for a one-week duration and amenorrhea for the previous three months. Abdominal examination showed a pelvic mass resembling a 15-week sized uterus. Serum ß-hCG levels were strongly increased, and abdomen ultrasound displayed an enlarged uterus with "snow-storm" features, compatible with the diagnosis of GTD. Laboratory data revealed suppressed TSH levels and high free thyroxine and free triiodothyronine levels (4 and 1.5 times above the upper limit of normality, respectively). Thyrotropin-receptor antibodies (TRAb) levels were negative, and thyroid ultrasound excluded major structural disease. She was managed with anti-thyroid drugs, Lugol's iodine, beta-blockers, and steroids during preoperative care. Thereafter, she underwent surgery, being diagnosed with a hydatidiform mole postoperatively. Her thyroid function returned to normal after three months, without the further need for antithyroid drugs. This case highlights the importance of considering GTD as an aetiology for thyrotoxicosis in perimenopausal women, especially in the absence of findings suggesting primary thyroid disease.

Gestational diabetes in twin pregnancy: A predictor of adverse fetomaternal outcomes?

AIM: To compare fetomaternal outcomes between GDM pregnant women with twin versus singleton pregnancies and then between women with GDM versus non-GDM twin pregnancies. METHODS: We performed a retrospective study including GDM pregnant women with both twin and singleton pregnancies followed in our tertiary center between 2011 and 2018. The fetomaternal characteristics of each group were compared. We then compared women with GDM twin pregnancy followed at our institution between 2011 and 2018 to non-GDM twin pregnant women giving childbirth in 2018. RESULTS: A total of 1127 GDM pregnant women were evaluated: 42 with twin pregnancy and 1085 with singleton pregnancy. Preeclampsia (14.3% vs. 3.3%, p < 0.001) and cesarean delivery (76.2% vs. 36.9%, p < 0.001) were more frequent among women with twin pregnancy. Neonatal morbidity was also more common among neonates delivered from twin pregnant women, including preterm labor (73.8% vs. 7.8%, p < 0.001), hypoglycemia (6% vs. 4.8%, p = 0.043), hyperbilirubinemia (33.3% vs. 9.0%, p < 0.001), RDS (28.6% vs. 2.7%, p < 0.001), admission in NICU (32.1% vs. 4.5%, p < 0.001) and SGA (19.0% vs. 11.0%, p = 0.001). Overall there were no significant differences in fetomaternal morbidity parameters between GDM (n = 42) versus non-GDM (n = 83) twin pregnancies, although SGA infants were more frequent in the latter group (33.9% vs. 19.0%, p = 0.014). CONCLUSIONS: In GDM pregnant women, twin pregnancy seems to be associated with an increased prevalence of neonatal morbidity when compared to singleton pregnancy. On the other hand, in twin pregnancy, diagnosis of GDM does not seem to be associated with poorer fetomaternal outcomes. GDM seems to be protective for the occurrence of SGA neonates in twin pregnancies.

Un caso poco habitual de diabetes / An uncommon cause of diabetes

Patients with Maturity Onset Diabetes of the Young (MODY) are often misclassified as having type 1 or type 2 diabetes and, as a result, are given inappropriate therapy. This case report aims to draw attention to MODY as a possible diagnosis in young diabetic patients. Biomarkers in combination with clinical characteristics, can help identify patients who should receive genetic testing. Rapid referral for genetic testing can avoid insulin use and establish optimal treatment. Furthermore, the knowledge of the genetic etiology will enable more-appropriate treatment, better prediction of disease progression, screening of family members and genetic counseling. (AU)

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes

ABSTRACT Objective: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. Materials and methods: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. Results: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). Conclusions: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Third trimester HbA1c and the association with large-for-gestational-age neonates in women with gestational diabetes.

OBJECTIVE: To evaluate the association between HbA1c levels measured in the third trimester and the risk for large for gestational age (LGA) in neonates of mothers affected by gestational diabetes mellitus (GDM). Secondarily, we aimed to identify an ideal cut-off for increased risk of LGA amongst pregnant women with GDM. METHODS: Observational retrospective review of singleton pregnant women with GDM evaluated in a diabetes and pregnancy clinic of a tertiary and academic hospital. From January/2011 to December/2017, 1,085 pregnant women underwent evaluation due to GDM, of which 665 had an HbA1c test in the third trimester. A logistic regression model was performed to evaluate predictors of LGA. A receiver-operating-characteristic (ROC) curve was used to evaluate the predictive ability of third trimester HbA1c for LGA identification. RESULTS: A total of 1,085 singleton pregnant women were evaluated during the study period, with a mean age of 32.9 ± 5.3 years. In the multivariate analysis, OGTT at 0 minutes (OR: 1.040; CI 95% 1.006-1.076, p = 0.022) and third trimester HbA1c (OR: 4.680; CI 95% 1.210-18.107, p = 0.025) were associated with LGA newborns. Using a ROC curve to evaluate the predictive ability of third trimester HbA1c for LGA identification, the optimal HbA1c cut-off point was 5.4% where the sensitivity was 77.4% and the specificity was 71.7% (AUC 0.782; p < 0.001). CONCLUSION: Few studies in the Mediterranean population have evaluated the role of HbA1c in predicting neonatal complications in women with GDM. A third trimester HbA1c > 5.4% was found to have good sensitivity and specificity for identifying the risk of LGA.

Cyanobacteria from freshwater lakes in the Azores archipelago, Portugal: data from long term phytoplankton monitoring.

BACKGROUND: The Azores are oceanic islands located in the Northern Atlantic Ocean and are particularly rich in aquatic systems, ranging from freshwater, brackish, marine and thermal habitats. Due to the increase in local anthropogenic pressures and global warming, several azorean lakes began to reveal signs of eutrophication that led to the implementation of monitoring programmes and management strategies on the most impacted lakes. Later, the Water Framework Directive (2000/60/EC) demanded the establishment of biomonitoring programmes for European freshwater ecosystems and the limited Azorean monitoring programmes were extended to a larger set of lakes. Since the establishment of the aquatic systems monitoring programme in the Azores archipelago, lakes have been regularly sampled, producing innumerous unpublished records of cyanobacteria that are difficult to access. NEW INFORMATION: Here we present the occurrences of cyanobacteria in Azorean lakes that result from 22 years of phytoplankton monitoring in a total of 1948 cyanobacteria occurrences from 968 phytoplankton sampling events on Azorean lakes done between 1996 and 2018 as part of regional inland aquatic ecosystems monitoring programmes. Forty two cyanobacteria taxa were identified in those events, 28 species and 14 at genus level. This information is crucial for conservation, biodiversity studies and lake management, as some of the cyanobacteria species present are bloom-forming and have the ability to produce toxins. This will also allow for the identification of invasive species and possible targeted control and mitigation programmes, according to the species present in the Azorean lakes.

Prenatal Diagnosis and Management of a Fetal Goiter Hypothyroidism due to Dyshormonogenesis.

Fetal goiter is a rare disorder not expected to be found during a healthy woman's pregnancy. It can be a prenatal manifestation of congenital hypothyroidism due to thyroid dyshormonogenesis and it can lead to serious perinatal complications. A vascularized fetal neck mass was detected at 29 weeks' gestation of a healthy primigravida. Magnetic resonance was suggestive of goiter causing airway deviation without polyhydramnios. Maternal thyroid function was normal and thyroid antibodies were negative. Two intra-amniotic levothyroxine infusions were performed at 32 and 33 weeks. Serial imaging control showed no progression of the mass. Elective caesarean section was performed at 38 weeks. The male newborn was admitted to the intensive care unit due to cardiorespiratory insufficiency with pulmonary hypertension. Hormonal assays revealed primary congenital hypothyroidism and ultrasonography confirmed diffuse goiter. Levothyroxine was started. Currently, he is 6 years old with adequate growth and normal psychomotor development. Genetic study found a heterozygous mutation in the TPO gene.

A telemedicine system that includes a personal assistant improves glycemic control in pump-treated patients with type 1 diabetes.

BACKGROUND: The DIABTel system, a Web-based telemedicine application, integrates a whole communication system (glucometer, insulin pump, wireless hand-held assistant) for medical remote advice. We sought to evaluate, in terms of glycemic control, the DIABTel system in a randomized crossover clinical study. METHODS: Ten patients with type 1 diabetes [5 women, age 40.6 (21-62) years, diabetes duration 14.7 (3-52) years] were included. During the 4-week active phase, data sent by patients were analyzed by the physician and modifications of the basal rate and bolus were advised in the following 24 hours. During the control phase, patients sent glucose data without any feedback from the medical center. RESULTS: The mean numbers of daily glucose values and bolus sent by patients during the active period were 4.46 +/- 0.91 and 4.58 +/- 0.89, respectively. The personal digital assistant functionalities used more frequently by patients were (times per week) data visualization (8.1 +/- 6.8), data download from the insulin pump (6.8 +/- 3.3), and synchronization with the telemedicine server (8.5 +/- 4.9). After the experimental phase, serum fructosamine decreased significantly (393 +/- 32 vs 366 +/- 25 micromol/liter; p < 0.05) and hemoglobin A1c (HbA1c) tended to decrease (8.0 +/- 0.6 vs 7.78 +/- 0.6; p = 0.073), whereas no changes were observed during the control phase. The number of treatment modifications proposed and performed by the patients correlated with the change observed in HbA1c during the active phase (r = -0.729, p = 0.017). CONCLUSIONS: The DIABTel system, a telemedicine system that includes a wireless personal assistant for remote treatment advising, allows better glycemic control in pump-treated patients with type 1 diabetes. To our knowledge, this is the first study that demonstrates improved glycemic control with the use of a telemedicine system that incorporates insulin delivery data.

[Evaluation of diabetic foot amputation rate]. / Avaliação da taxa de amputações. Consulta multidisciplinar do pé diabético.

In 1987, it was created the first portuguese Diabetic Foot Clinic in Oporto, at the Hospital Geral de Santo António. The distinction between neuropathic and ischaemic foot was the key stone to reduce drastically the rate of major amputations in the first two years of activity. Since then and until 1995 the rate of major amputations had stabilised around 8%. The aim of the present study was to evaluate if there was any change in the last three years. A retrospective study was performed reviewing the clinical files of 843 new patients between 1998 and 2000. The 593 patients who presented with a foot ulcer with or without infection were selected: 60.4% with neuropathic foot and 39.6% with ischaemic one. Overall, 31 of the 593 patients with ulcer or infection were treated with major amputation (5.2%). There was a statistical difference between the major amputation outcome among the two types of foot (p < 0.001). Necrosis showed to carry a poor prognosis (30.7% in ischaemic foot vs 8,3% in neuropathic, p = 0.024). There was no further statistical significance for age, sex, type or duration of diabetes as risk factors for major amputation. This retrospective study has showed a slight reduction in the rate of major amputations since 1995. Poor prognosis was related to necrosis and ischaemic foot. Further improvement requires harder investment in patients' education, as well as in alerting the primary health care physicians, for the most unpredictable catastrophic complication of diabetes.