Fatty liver index is an independent risk factor for all-cause mortality and major cardiovascular events in type 1 diabetes: an 11-year observational study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. METHODS: We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. RESULTS: Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was < 30 in 515 subjects (66.5%), 30-59 in 169 (21.8%), and ≥ 60 in 90 (11.6%). Mortality increased steeply with FLI: 3.9, 10.1, 22.2% (p < 0.0001). In unadjusted Cox analysis, compared to FLI < 30, risk of death increased in FLI 30-59 (HR 2.85, 95% CI 1.49-5.45, p = 0.002) and FLI ≥ 60 (6.07, 3.27-11.29, p < 0.0001). Adjusting for Steno Type 1 Risk Engine (ST1-RE; based on age, sex, DD, systolic BP, LDL cholesterol, HbA1c, albuminuria, eGFR, smoking and exercise), HR was 1.52 (0.78-2.97) for FLI 30-59 and 3.04 (1.59-5.82, p = 0.001) for FLI ≥ 60. Inclusion of prior CV events slightly modified HRs. FLI impact was confirmed upon adjustment for EURODIAB Risk Engine (EURO-RE; based on age, HbA1c, waist-to-hip ratio, albuminuria and HDL cholesterol): FLI 30-59: HR 1.24, 0.62-2.48; FLI ≥ 60: 2.54, 1.30-4.95, p = 0.007), even after inclusion of prior CVD. CV events incidence increased with FLI: 3.5, 10.5, 17.2% (p < 0.0001). In unadjusted Cox, HR was 3.24 (1.65-6.34, p = 0.001) for FLI 30-59 and 5.41 (2.70-10.83, p < 0.0001) for FLI ≥ 60. After adjustment for ST1-RE or EURO-RE, FLI ≥ 60 remained statistically associated with risk of incident CV events, with trivial modification with prior CVD inclusion. CONCLUSIONS: This observational prospective study shows that FLI is associated with higher all-cause mortality and increased risk of incident CV events in type 1 diabetes.

Assisted reproductive technology, risk of gestational diabetes, and perinatal outcomes in singleton pregnancies.

AIMS: To evaluate the impact of assisted reproductive technology (ART) on the risk of gestational diabetes mellitus (GDM) in single pregnancies. MATERIALS AND METHODS: We retrospectively collected clinical and anthropometric data of 219ART- and 256 age- and body mass index (BMI)-matched women with spontaneous conception screened for GDM. The primary outcome was to evaluate GDM prevalence in ART women. RESULTS: There were no differences in age, BMI, and family history of diabetes in the two groups of women. ART-women were more frequently primiparous, whereas the prevalence of previous GDM was higher in SC-women. The prevalence of GDM in the whole cohort was 36.1% and was higher in ART-women (52.3% vs. 23.4%; p < 0.0001). In the whole cohort, on multivariate analysis, family history of diabetes (OR 1.67; 95% CI: 1.03-2.69), previous GDM (OR 7.05; 95% CI: 2.92-17.04), pre-pregnancy obesity (OR 2.72; 95% CI 1.21-6.13), and ART (OR 4.14; 95% CI 2.65-6.48) were independent risk factors for GDM. Among ART-women, age over 40 years was associated with GDM. Preterm delivery was more common in ART-women; gestational week at delivery, birth weight, ponderal index, and Apgar score were lower in ART-women than in SC-women, both in the whole cohort and in GDM women. CONCLUSIONS: Among women undergoing ART treatment, at least one in two develops GDM. ART appears to be an independent risk factor for GDM in single pregnancies, particularly above the age of 40. ART treatment seems to be associated with an increased rate of preterm delivery and lower neonatal birth weight and Apgar score, especially in GDM women. CLINICAL TRIAL REGISTRATION: The study was not registered as it is an observational retrospective evaluation.

Exercise during pregnancy: how much active are pregnant women at risk of gestational diabetes despite few contraindications?

INTRODUCTION: Diet and physical activity are cornerstones in prevention and treatment of Gestational Diabetes (GDM) though some caution may be required under specific circumstances. The aims of this study were to evaluate activity habits during pregnancy and contraindications to physical activity in women at risk for GDM. METHODS: 536 pregnant women (age 35 ± 5 years; gestation week 25 ± 4; pre-pregnancy BMI 24.6 ± 12.9 kg/m2), selective screened for GDM, filled out a standardized questionnaire recording physical activity during pregnancy. RESULTS: Of 536 women, 73.4% reported regular exercise before pregnancy and 95.5% of them continued during pregnancy. 8.2% had absolute contraindications to exercise, such as placenta praevia /vaginal bleeding and incompetent cervix/cerclage. Physical activity during the last month was reported by 66.2% of women; frequency was 1-2 times/week (44%); intensity was light (83%) and duration on average (44%) 20-40 min/day. 48% of women spent most of their time in sedentary behaviors (sitting). Among women with GDM, physical activity was associated with better metabolic profile and lower needed of insulin therapy. CONCLUSION: Women at risk for GDM spent most of their time in sedentary behaviors, despite a low prevalence of contraindications to exercise. Therefore, our data call for the need of motivational counseling aimed to implement physical activity during pregnancy.

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study.

BACKGROUND: Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS: Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS: In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations.

Exercise has been proved to be safe during pregnancy and to offer benefits for both mother and fetus; moreover, physical activity may represent a useful tool for gestational diabetes prevention and treatment. Therefore, all women in uncomplicated pregnancy should be encouraged to engage in physical activity as part of a healthy lifestyle. However, exercise in pregnancy needs a careful medical evaluation to exclude medical or obstetric contraindications to exercise, and an appropriate prescription considering frequency, intensity, type and duration of exercise, to carefully balance between potential benefits and potential harmful effects. Moreover, some precautions related to anatomical and functional adaptations observed during pregnancy should be taken into consideration. This review summarized the suggested recommendations for physical activity among pregnant women with focus on gestational diabetes.

How much weight are women gaining during pregnancy? An Italian cohort study.

INTRODUCTION: The 2009 Institute of Medicine (IOM) guidelines define adequate gestational weight gain (GWG) in the attempt to prevent maternal and neonatal adverse outcomes. The aim of this study was to assess whether the IOM guidelines are met in pregnant women with different pre-gestational body mass index (BMI). METHODS: The study included 230 pregnant women recruited at the University Hospital of Pisa (Italy) at their screening visit (24-28 weeks of gestation) for gestational diabetes (GDM). GWG was determined at screening time and before delivery to be compared with GWG recommended by IOM for each pre-pregnancy BMI category. RESULTS: A total of 48% of women had a GWG exceeding IOM recommendations. The prevalence of GWG excess was higher in over-weight (OW, 63.2%) and obese (OB, 63.8%) women as compared to normal-weight (NW, 27.7%; p < 0.0001) women. The upper limit of the recommended IOM weight gain range was already exceeded at screening time in 15.5% of women. The percentage increased 27% and 18% in OW and OB, respectively, compared with 1.5% in NW (p < 0.001). CONCLUSION: About half of pregnant women had a GWG greater than the IOM recommended. GWG excess is particularly evident in OW and OB women.

Accuracy of intermittently scanned continuous glucose monitoring during caesarean delivery in pregnant women with insulin-treated diabetes.

AIM: Continuous Glucose Monitoring (CGM) systems are not currently recommended to guide intrapartum glucose and insulin infusion, due to insufficient data. In this study, intrapartum accuracy of intermittently scanned CGM (isCGM), compared to simultaneously measured capillary glucose (CG), was evaluated. METHODS: Paired isCGM (Freestyle Libre 2) - CG data during caesarean delivery in pregnant women with insulin-treated diabetes were prospectively collected. The isCGM accuracy was assessed by MARD and Clarke Error Grid analysis. Moreover, the impact on intrapartum management was evaluated. RESULTS: Sixty-eight paired isCGM-CG data of 19 women were evaluated. The overallMARD was 9.28 %. All values were in A and B zones of Clarke Error Grid. Forty-six (68 %) isCGM-CG pairs were in the same glycemic range, meaning the same intrapartum management. All discordant data were identified by checking CG in case of isCGM above 110 mg/dL or less than 70 mg/dL [chi-square 21.76, p < 0.001]. At ROC curve, isCGM above 110 mg/dL was associated with 100 % sensitivity to discordant result at CG (AUC 0.859, p < 0.001). CONCLUSION: The accuracy of isCGM during caesarean delivery was good, particularly for glucose values between 70 and 110 mg/dL, when CG confirmation could be safely avoided.

Advances in diabetes management: have pregnancy outcomes in women with type 1 diabetes changed in the last decades?

AIMS: Over the recent years multiple therapeutic and management opportunities have been made available to treat pregnant women with Type 1 diabetes (T1DM). However, analyses assessing whether these different approaches may have any specific advantage/disadvantage in metabolic control and neonatal outcomes is still limited. The aim of this study was to compare metabolic control and neonatal outcomes in pregnant women with T1DM among different basal insulins (NPH vs. analogue), insulin administration ways [Multiple Daily Injections (MDI) vs. Continuous Subcutaneous Insulin Infusion (CSII)] and glucose monitoring systems [Self-Monitoring of Blood Glucose (SMBG) vs. real-time/intermittently scanned Continuous Glucose Monitoring (rtCGM/isCGM)]. METHODS: A retrospective analysis on metabolic data and neonatal outcomes of 136 T1DM pregnant women (76% on MDI, based on NPH (51%) or analogue (49%); 24% on CSII; 24% using rtCGM/isCGM), managed between 2008 and 2020, was performed, comparing different therapeutic approaches. RESULTS: Metabolic data and neonatal outcomes were comparable among women treated with different basal insulins. Women on CSII planned their pregnancy more frequently (82 vs. 60%; p = 0.043) and had better pregestational HbA1c (52 ± 5 vs. 60 ± 13 mmol/mol; p = 0.044) and first trimester HbA1c (48 ± 4 vs. 51 ± 8 mmol/mol; p = 0.047). Pregestational and first trimester HbA1c were also lower in women using rtCGM/isCGM (53 ± 8 vs. 58 ± 13 mmol/mol; p = 0.027 and 46 ± 5 vs. 51 ± 7 mmol/mol; p = 0.034, respectively). In the whole cohort, LGA risk was directly correlated to HbA1c at third trimester (correlation coefficient: 0.335, p = 0.001) and inversely correlated to the achievement of HbA1c target (≤6% [<42 mmol/mol]) at third trimester (correlation coefficient: - 0.367, p < 0.001). CONCLUSION: Treatment with insulin analogs didn't significantly change metabolic control and neonatal outcomes in T1DM women, while CSII and rtCGM/isCGM can optimize preconception and first trimester pregnancy glycemic control. Irrespective of the therapeutic management, third trimester HbA1c remains the strongest risk factor for LGA.

Efficacy of Dulaglutide in a Patient With Type 2 Diabetes, High Cardiovascular Risk, and HIV: A Case Report.

Background: Type 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available. Case Description: A 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects. Conclusion: This case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals.

Insulin discovery: A pivotal point in medical history.

The discovery of insulin in 1921 - due to the efforts of the Canadian research team based in Toronto - has been a landmark achievement in the history of medicine. Lives of people with diabetes were changed forever, considering that in the pre-insulin era this was a deadly condition. Insulin, right after its discovery, became the first hormone to be purified for human use, the first to be unraveled in its amino acid sequence and to be synthetized by DNA-recombinant technique, the first to be modified in its amino acid sequence to modify its duration of action. As such the discovery of insulin represents a pivotal point in medical history. Since the early days of its production, insulin has been improved in its pharmacokinetic and pharmacodynamic properties in the attempt to faithfully reproduce diurnal physiologic plasma insulin fluctuations. The evolution of insulin molecule has been paralleled by evolution in the way the hormone is administered. Once-weekly insulins will be available soon, and glucose-responsive "smart" insulins start showing their potential in early clinical studies. The first century of insulin as therapy was marked by relentless search for better formulations, a search that has not stopped yet. New technologies may have, indeed, the potential to provide further improvement of safety and efficacy of insulin therapy and, therefore, contribute to improvement of the quality of life of people with diabetes.

Behavior during aging of bone-marrow fatty-acids profile in women's calcaneus to search for early potential osteoporotic biomarkers: a 1H-MR Spectroscopy study.

AIM: Identify new potential biomarkers of osteoporosis at an early stage, by magnetic resonance spectroscopy (MRS), studying early changes in the metabolic profile of bone-marrow fatty acids in women's calcanei during healthy aging and osteoporosis status. METHODS: Single voxel MRS was performed by using a point resolved spectroscopy (PRESS) sequence at 3T. Thirty-four Caucasian women (age range: 22-59 years) were recruited to investigate calcaneus bone marrow. The cohort was constituted of four groups according to age, menopausal status, and T-score evaluated after a DXA examination on the femoral neck. Women were classified in young control (n = 11, mean age = 26.5 ± 3.8 y, age range: 22-34 years), perimenopausal groups (n = 11, mean age = 42.0 ± 3.6 y, age range: 37-47 years), postmenopausal group (n = 9, mean age = 55.4 ± 2.9 y, age range: 50-59 years, mean T-score = -1.70 ± 0.50) and osteoporotic group (n = 6, mean age = 53.0 ± 2.8 y, age range: 50-58 years, mean T-score = -2.54 ± 0.10). The total lipid content (TL), the Unsaturation Index (UI), and the fraction of unsaturated/polyunsaturated fatty acid (fUFA and fPUFA) were calculated. RESULTS: TL was significantly correlated with age (r = 0.73, p < 0.001). TL increases linearly with age in the young + perimenopausal population (r = 0.92, p < 0.001) but this trend is not significant in the postmenopausal subject (r = 0.48, p = 0.07). No significant correlation was found between T-Score and TL in postmenopausal and osteoporotic women, whereas a significant correlation was found between TL and time interval (tp) between the age at menopause and the age of the subject at the MRS examination. Conversely, no correlation was found between T-score and tp. The unsaturation index (UI) does not significantly discriminate between osteoporotic, peri- and postmenopausal women. On the other hand, fUFA is significantly different in peri-menopausal and osteoporotic subjects (p = 0.02), while fPUFA is significantly different both between peri- and postmenopausal women (p = 0.05) and postmenopausal and osteoporotic subjects (p = 0.03). Both fUFA and fPUFA did not correlate with subjects' age. CONCLUSION: In the female calcaneus, fUFA and fPUFA are promising measurable quantities for the characterization of bone marrow's composition potentially correlated with the development of osteoporosis, whereas UI does not differentiate between subjects of varying osteoporotic status. The fact that the TL in the calcaneus is correlated with tp, indicates that active metabolic changes are still occurring in these subjects, giving complementary information to the DXA about the changes in bone marrow's composition which may affect the whole bone health.

Use of non-nutritive-sweetened soft drink and risk of gestational diabetes.

In this observational study, we assessed the association between use of non-nutritive-sweetened soft drink (NNSSD) and risk of gestational diabetes (GDM) in 376 pregnant women consecutively screened for GDM, observing that NNSSD consumption is common among pregnant women and is associated with an increased risk of GDM, independently from traditional risk factors.

Glycaemic control during the lockdown for COVID-19 in adults with type 1 diabetes: A meta-analysis of observational studies.

AIMS: To assess the effects of lockdown due to COVID-19 pandemic on glucose metrics, measured by glucose monitoring systems, in adult individuals with type 1 diabetes. METHODS: We conducted a systematic literature search for English language articles from MEDLINE, Scopus and Web of Science up to February 28, 2021, using "diabetes", "lockdown", and "glucose" as key search terms. Time in range (TIR) was the main outcome; other metrics were time above range (TAR), time below range (TBR), mean blood glucose (MBG) and its variability (%CV), estimated HbA1c (eA1c) or glucose management indicator (GMI). RESULTS: Seventeen studies for a total of 3,441 individuals with type 1 diabetes were included in the analysis. In the lockdown period, TIR 70-180 mg/dl increased by 3.05% (95% CI 1.67-4.43%; p < 0.0001) while TAR (>180 mg/dL and > 250 mg/dL) declined by 3.39% (-5.14 to -1.63%) and 1.96% (-2.51 to -1.42%), respectively (p < 0.0001 for both). Both TBR < 70 and <54 mg/dL remained unchanged. MBG slightly decreased by 5.40 mg/dL (-7.29 to -3.51 mg/dL; p < 0.0001) along with a reduction in %CV. Pooled eA1c and GMI decreased by 0.18% (-0.24 to -0.11%; p < 0.0001) and a similar reduction was observed when GMI alone was considered (0.15%, -0.23 to -0.07%; p < 0.0001). Sensor use was only slightly but not significantly reduced during lockdown. CONCLUSIONS: This meta-analysis shows that well-controlled people with type 1 diabetes on both MDI and CSII with continuous or flash glucose monitoring did not experience a deterioration in glucose control throughout the COVID-19 lockdown, showing a modest, though statistically significant improvement in many glucose control parameters.

Impact of COVID-19 lockdown on glucose control of elderly people with type 2 diabetes in Italy.

AIMS: to evaluate the effect of home confinement related to COVID-19 lockdown on metabolic control in subjects with T2DM in Italy. METHODS: we evaluated the metabolic profile of 304 individuals with T2DM (65% males; age 69 ± 9 years; diabetes duration 16 ± 10 years) attending our Diabetes Unit early at the end of lockdown period (June 8 to July 7, 2020) and compared it with the latest one recorded before lockdown. RESULTS: There was no significant difference in fasting plasma glucose (8.6 ± 2.1 vs 8.8 ± 2.5 mmol/L; P = 0.353) and HbA1c (7.1 ± 0.9 vs 7.1 ± 0.9%; P = 0.600) before and after lockdown. Worsening of glycaemic control (i.e., ΔHbA1c ≥ 0.5%) occurred more frequently in older patients (32.2% in > 80 years vs 21.3% in 61-80 years vs 9.3% in < 60 years; P = 0.05) and in insulin users (28.8 vs 16.5%; P = 0.012). On multivariable analysis, age > 80 years (OR 4.62; 95%CI: 1.22-16.07) and insulin therapy (OR 1.96; 95%CI: 1.10-3.50) remained independently associated to worsening in glycaemic control. CONCLUSIONS: Home confinement related to COVID-19 lockdown did not exert a negative effect on glycaemic control in patients with T2DM. However, age and insulin therapy can identify patients at greatest risk of deterioration of glycaemic control.

A fully implantable device for intraperitoneal drug delivery refilled by ingestible capsules.

Creating fully implantable robots that replace or restore physiological processes is a great challenge in medical robotics. Restoring blood glucose homeostasis in patients with type 1 diabetes is particularly interesting in this sense. Intraperitoneal insulin delivery could revolutionize type 1 diabetes treatment. At present, the intraperitoneal route is little used because it relies on accessing ports connecting intraperitoneal catheters to external reservoirs. Drug-loaded pills transported across the digestive system to refill an implantable reservoir in a minimally invasive fashion could open new possibilities in intraperitoneal delivery. Here, we describe PILLSID (PILl-refiLled implanted System for Intraperitoneal Delivery), a fully implantable robotic device refillable through ingestible magnetic pills carrying drugs. Once refilled, the device acts as a programmable microinfusion system for precise intraperitoneal delivery. The robotic device is grounded on a combination of magnetic switchable components, miniaturized mechatronic elements, a wireless powering system, and a control unit to implement the refilling and control the infusion processes. In this study, we describe the PILLSID prototyping. The device key blocks are validated as single components and within the integrated device at the preclinical level. We demonstrate that the refilling mechanism works efficiently in vivo and that the blood glucose level can be safely regulated in diabetic swine. The device weights 165 grams and is 78 millimeters by 63 millimeters by 35 millimeters, comparable with commercial implantable devices yet overcoming the urgent critical issues related to reservoir refilling and powering.

Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade.

CONTEXT: Thyrotoxicosis is a common immune-related adverse event in patients treated with programmed cell death protein-1 (PD1) or programmed cell death protein ligand-1 (PD-L1) blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy, is lacking, as are data on response to treatment and follow-up. OBJECTIVE: The aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment. METHODS: We conducted a retrospective study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis on PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mtechnecium scintiscan, and longitudinal thyroid function tests. RESULTS: Five patients had normal or increased scintigraphic uptake (Sci+), no serum antibodies against the thyrotropin receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N = 9) or euthyroidism (N = 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P = .04). Among Sci- individuals, a larger thyroid volume was associated with a longer time to remission (P < .05). Methimazole (MMI) was effective only in Sci+ individuals (P < .05). CONCLUSION: Administration of PD1- or PD-L1-blocking antibodies may induce 2 different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2, characterized by destructive and transient thyrotoxicosis that evolves to hypothyroidism or euthyroidism. Thyroid scintigraphy and ultrasound help in differentiating and managing these 2 forms of iatrogenic thyrotoxicosis.

Continuous subcutaneous insulin infusion and multiple dose insulin injections in Type 1 diabetic pregnant women: a case-control study.

The aim of this study was to evaluate the effects of continuous subcutaneous insulin infusion (CSII) on glycemic control and pregnancy outcomes in Type 1 diabetic pregnant women. We retrospectively evaluated 42 subjects, 20 treated with CSII and 22 with multiple dose insulin injections (MDI). The two groups were comparable for age, pre-pregnancy BMI, and primiparous rate, whereas women in the CSII group showed a tendency toward a longer diabetes duration (p = 0.06). Pre-pregnancy diabetic retinopathy and/or nephropathy were present in nine women of CSII and three of MDI. In all women metabolic control improved during pregnancy, without differences between the two groups and at the end of gestation HbA1c was 6.3 +/- 0.6 in CSII and 6.1 +/- 1.1% in MDI. Moreover, there were no differences in weight gain, whereas insulin requirement resulted significantly (p = 0.009) lower in CSII than in MDI. We recorded only one severe hypoglycaemic episode in both groups. No cases of deteriorations of the chronic diabetic complications were observed. The delivery occurred at 36.4 +/- 2.2 weeks; birth weight, the rate of large for gestational age, and the parameters of foetal morbidity were similar in both groups. In conclusions, CSII and MDI are both effective in improving maternal glucose control and have both similar pregnancy outcomes.

Type 1 diabetes and COVID-19: The "lockdown effect".

AIMS: The aim of this study was to evaluate the effect the lockdown imposed during COVID-19 outbreak on the glycemic control of people with Type 1 diabetes (T1D) using Continuous (CGM) or Flash Glucose Monitoring (FGM). MATERIALS AND METHODS: We retrospectively analyzed glucose reading obtained by FGM or CGM in T1D subjects. Sensor data from 2 weeks before the lockdown (Period 0, P0), 2 weeks immediately after the lockdown (period 1, P1), in mid-lockdown (Period 2, P2) and immediately after end of lockdown (Period 3, P3) were analyzed. RESULTS: The study included 63 T1D patients, (FGM: 52, 82%; CGM:11, 18%). Sensor use (91%) were slightly reduced. Despite this reduction, Time in Range increased in P1 (62%), P2 (61%) and P3 (62%) as compared to P0 (58%, all p < 0.05 or less) with concomitant reduction in the Time Above Range (P0: 38%; P1: 34%, P2: 34%, P3: 32%, all p < 0.05 or less vs. P0). Average glucose and GMI improved achieving statistical difference in P3 (165 vs. 158 mg/dl, p = 0.040 and 7.2% (55 mmol/mol) vs. 7.0% (53 mmol/mol), p = 0.016) compared to P0. Time Below Range (TBR) and overall glucose variability remained unchanged. Bi-hourly analysis of glucose profile showed an improvement particularly in the early morning hours. CONCLUSIONS: In T1D subjects with good glycemic control on CGM or FGM, the lockdown had no negative impact. Rather a modest but significant improvement in glycemic control has been recorded, most likely reflecting more regular daily life activities and reduces work-related distress.

Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study.

OBJECTIVE: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]). RESULTS: Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, P = 0.079) vs. Q1. CONCLUSIONS: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.

Freestyle Libre trend arrows for the management of adults with insulin-treated diabetes: A practical approach.

Freestyle Libre (FSL) system is a new method to detect glucose enabling a new paradigm in glucose monitoring and self-management. The sensor, reading the interstitial fluid glucose concentration, provides a numerical data of glucose level and a trend arrow that add context to static measurement of glucose level. Therefore, patients could easily follow the progression of their glucose levels over the time, allowing early detection and timely treatment of deviations from targeted glucose level range, thus preventing extreme fluctuations. In order to take full advantage of the system both the caregiver and the person with diabetes must appreciate the need of careful interpretation of the data generated by the FSL. To this purpose we have generated recommendations that are based on methods suggested for CGM, our clinical experience and discussion with experienced patients using FSL, to provide a pragmatic approach to use FSL trend arrow data for managing diabetes in adults.