TPO antibody status prior to first radioactive iodine therapy as a predictive parameter for hypothyroidism in Graves' disease.

Objective: We investigated whether a positive thyroid peroxidase antibody (TPO Ab) status before radioactive iodine (RAI) therapy in patients with Graves' hyperthyroidism is a predictive factor for developing hypothyroidism post RAI. Methods: We performed a retrospective study of patients with Graves' hyperthyroidism with known TPO Ab status, receiving the first administration of RAI. Patients from four thyroid outpatient centres in Belgium receiving their first RAI therapy between the years 2011 and 2019 were studied. Clinical, laboratory, imaging, and treatment data were recorded from medical charts. Hypothyroidism and cure (defined as combined hypo- and euthyroidism) were evaluated in period 1 (≥2 and ≤9 months, closest to 6 months post RAI) and period 2 (>9 months and ≤24 months post RAI, closest to 12 months post RAI). Results: A total of 152 patients were included of which 105 (69%) were TPO Ab-positive. Compared to TPO Ab-negative patients, TPO Ab-positive patients were younger, had a larger thyroid gland, and had more previous episodes of hyperthyroidism. In period 1, 89% of the TPO Ab-positive group developed hypothyroidism and 72% in the TPO Ab-negative group (P = 0.007). In period 2, the observation was similar: 88% vs 72% (P = 0.019). In the multivariate logistic regression analysis, a positive TPO Ab status was associated with hypothyroidism in period 2 (adjusted OR: 4.78; 95% CI: 1.27-20.18; P = 0.024). In period 1, the aOR was 4.16 (95% CI: 1.0-18.83; P = 0.052). Conclusion: A positive TPO Ab status in patients with Graves' hyperthyroidism receiving the first administration of RAI is associated with a higher risk of early hypothyroidism.

Real-world Evidence of Efficacy and Safety of SGLT2 Inhibitors as Adjunctive Therapy in Adults With Type 1 Diabetes: A European Two-Center Experience.

OBJECTIVE: To evaluate real-world efficacy and safety of sodium-glucose cotransporter 2 inhibitor (SGLT2i) use in combination with insulin in people with type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort European two-center study. Data on demographics, HbA1c, weight, insulin use, renal function, and adverse events were collected for 199 adults with type 1 diabetes who initiated a SGLT2i adjunct to insulin. Subgroup analyses were performed to identify who benefited most and who was more at risk for adverse events. RESULTS: Overall, significant reductions in mean HbA1c (-0.5%), weight (-2.9 kg), and daily insulin (-8.5%) were achieved after 12 months. The greatest reduction in HbA1c was obtained in individuals with baseline HbA1c >8% (-0.7% [64 mmol/mol]). The most weight loss was observed in subjects with BMI >27 kg/m2 (-3.5 kg). Individuals with baseline estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 showed an increase in eGFR (4.5 mL/min/1.73 m2), whereas those with urinary albumin-to-creatinine ratio (UACR) >15 mg/g showed a decrease in UACR (-16.6 mg/g). Fifty-seven individuals (28.6%) reported adverse events: 45 with genital infections (22.6%), 5 ketosis episodes (2.5%), and 7 diabetic ketoacidosis (DKA) (3.5%). No severe hypoglycemia events were reported. CONCLUSIONS: Our real-world data on SGLT2i showed promising results in reductions in HbA1c, weight, and insulin requirements in type 1 diabetes. Benefits were more pronounced in individuals with higher baseline HbA1c and BMI. DKA remained a major concern, despite educational measures. Further real-life evidence is still required for evaluation of SGLT2i longer-term effects and their impact on reno-cardiovascular outcomes.

Liraglutide for Weight Management in the Real World: Significant Weight Loss Even if the Maximal Daily Dose Is Not Achieved.

INTRODUCTION: Obesity is a global health challenge, and pharmacologic options are emerging. Once daily subcutaneous administration of 3 mg liraglutide, a glucagon like peptide-1 analogue, has been shown to induce weight loss in clinical trials, but real-world effectiveness data are scarce. METHODS: It is a single-centre retrospective cohort study of patients who were prescribed liraglutide on top of lifestyle adaptations after multidisciplinary evaluation. In Belgium, liraglutide is only indicated for weight management if the BMI is >30 kg/m2 or ≥27 kg/m2 with comorbidities such as dysglycaemia, dyslipidaemia, hypertension, or obstructive sleep apnoea. No indication is covered by the compulsory health care insurance. Liraglutide was started at 0.6 mg/day and uptitrated weekly until 3 mg/day or the maximum tolerated dose. Treatment status and body weight were evaluated at the 4-month routine visit. RESULTS: Between June 2016 and January 2020, liraglutide was prescribed to 115 patients (77% female), with a median age of 47 (IQR 37.7-54.0) years, a median body weight of 98.4 (IQR 90.0-112.2) kg, a BMI of 34.8 (IQR 32.2-37.4) kg/m2, and an HbA1c level of 5.6%. Five (4%) patients did not actually initiate treatment, 9 (8%) stopped treatment, and 8 (7%) were lost to follow-up. At the 4-month visit, the median body weight had decreased significantly by 9.2% to 90.8 (IQR 82.0-103.5) kg (p < 0.001). Patients using 3.0 mg/day (n = 60) had lost 8.0 (IQR 5.8-10.4) kg. The weight loss was similar (p = 0.9622) in patients that used a lower daily dose because of intolerance: 7.4 (IQR 6.2-9.6) kg for 1.2 mg (n = 3), 7.8 (IQR 4.1-7.8) kg for 1.8 mg (n = 16), and 9.0 (IQR 4.8-10.7) kg for 2.4 mg/day (n = 14). Weight loss was minimal if liraglutide treatment was not started or stopped prematurely (median 3.0 [IQR 0.3-4.8] kg, p < 0.001, vs. on treatment). Further analysis showed an additional weight reduction of 1.8 kg in the patients that had started metformin <3 months before the start of liraglutide (p < 0.001). The main reasons for liraglutide discontinuation were gastrointestinal complaints (n = 5/9) and drug cost (n = 2/9). CONCLUSION: In this selected group of patients, the majority complied with liraglutide treatment over the initial 4-month period and achieved a significant weight loss, irrespective of the maximally tolerated maintenance dose. Addition of metformin induced a small but significant additional weight loss.

Risk for ketonaemia in type 1 diabetes pregnancies with sensor-augmented pump therapy with predictive low glucose suspend compared with low glucose suspend: a crossover RCT.

AIMS: To determine the frequency of ketonaemia in pregnant women with type 1 diabetes treated with a sensor-augmented pump (SAP) in predictive low glucose suspend (PLGS) mode compared with low glucose suspend (LGS) mode. METHODS: An open-label crossover pilot RCT in ten women with type 1 diabetes treated with a 640 Medtronic insulin pump, with inclusion between 12-30 weeks of pregnancy. Participants were 1/1 randomly assigned (allocation by statistician using a permuted block size of 2) to either 2 weeks with an SAP in PLGS mode or 2 weeks in LGS mode. After the first 2 weeks, participants were switched to the other mode. Ketones in the participants' serum were measured three times daily (fasting, midday and evening) during the 4 weeks. The primary endpoint was the frequency of blood ketones > 0.6 mmol/l. Participants and healthcare providers were not blinded to group assignment for assessment of outcomes. RESULTS: The median gestational week at inclusion was 12.5 weeks (12.0-15.0), participants had a median age of 31.5 years (24.0-33.0), BMI of 26.6 kg/m2 (24.5-31.8), baseline HbA1c of 41 mmol/mol (40-43; 5.9% [5.8-6.1]) and baseline time in range (TIR, 3.5-7.8 mmol/l) of 64.6% (55.6-68.7). Comparing the LGS mode with the PLGS mode, insulin suspension time per day was 2.0 h (1.3-2.3) vs 3.5 h (3.3-5.0; p = 0.002), ketonaemia > 0.6 mmol/l was 0% vs 0.5% (p = 1.000) and no participants had ketonaemia > 1 mmol/l. TIR on LGS was 64.7% (58.0-68.7) vs 61.1% (56.5-67.5) on PLGS (p = 0.492), time < 3.5 mmol/l was higher on LGS at 7.5% (4.6-8.3) vs 4.2% (2.4-6.9) on PLGS (p = 0.014). Treatment satisfaction and fear for hypoglycaemia were similar whether using LGS or PLGS mode. CONCLUSIONS/INTERPRETATION: Despite longer time periods with suspended insulin delivery, pregnant women using an SAP in PLGS mode were not at higher risk of developing ketonaemia compared with those in LGS mode. Women with an SAP in PLGS mode had similar TIR with less time in hypoglycaemia. TRIAL REGISTRATION: Clinical Trials NCT04292509 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.