ObjectiveWe aimed to investigate the effect of liraglutide treatment on heart function in type 2 diabetes (T2D) patients with subclinical heart failure.MethodsRandomized open parallel-group trial. 62 T2D patients (45 male) with subclinical heart failure were randomized to either once daily liraglutide 1.8 mg, or glimepiride 4 mg, both add on to metformin 1 g twice a day. Mitral annular systolic (s′) and early diastolic (e′) velocities were measured at rest and during bicycle ergometer exercise, using tissue Doppler echocardiography. The primary endpoint was 18-week treatment changes in longitudinal functional reserve index (LFRIdiastolic/systolic).ResultsClinical characteristics between groups (liraglutide = 33 vs. glimepiride = 29) were well matched. At baseline left ventricle ejection fraction (53.7 vs. 53.6%) and global longitudinal strain (−15.3 vs. −16.5%) did not differ between groups. There were no significant differences in mitral flow velocities between groups. For the primary endpoint, there was no treatment change [95% confidence interval] for: LFRIdiastolic (−0.18 vs. −0.53 [−0.28, 2.59; p = 0.19]), or LFRIsystolic (−0.10 vs. −0.18 [−1.0, 1.7; p = 0.54]); for the secondary endpoints, there was a significant treatment change in respect of body weight (−3.7 vs. −0.2 kg [−5.5, −1.4; p = 0.001]), waist circumference (−3.1 vs. −0.8 cm [−4.2, −0.4; p = 0.019]), and heart rate (HR) (6.3 vs. −2.3 bpm [−3.0, 14.2; p = 0.003]), with no such treatment change in hemoglobin A1c levels (−11.0 vs. −9.2 mmol/mol [−7.0, 2.6; p = 0.37]), between groups.Conclusion18-week treatment of liraglutide compared with glimepiride did not improve LFRIdiastolic/systolic, but however increased HR. There was a significant treatment change in body weight reduction in favor for liraglutide treatment.

Gene variants of CYP24A1, which encodes the enzyme 24-hydroxylase, are a most unusual cause of maternal hypercalcemia. Loss-of-function mutations in CYP24A1 result in impaired dehydroxylation of active vitamin D (calcitriol). Secondary to this hypercalcemia, hypercalciuria and suppressed parathyroid hormone (P-PTH) can develop. These gene-variants are most often detected in children exposed to vitamin D prophylaxis. These children develop failure to thrive, hypercalciuria, hypercalcemia, and low PTH levels. CYP24A1 variants have also been reported in adults with hypercalcemia and recurrent urolithiasis. This report describes gestational hypercalcemia in two of three sisters with combined CYP24A1 heterozygous variants.MethodsWe retrospectively investigated medical files, clinical information, and calcium levels during and after pregnancy in three sisters giving birth to nine children. All three sisters were also tested genetically.ResultsTwo sisters developed hypercalcemia during all seven pregnancies and late-onset hypertension during pregnancy. These sisters had two heterozygote variants in the enzyme CYP24A1: c1186C>T and c443T>C. A third sister had the c1186C>T variant and was normocalcemic. Of the seven children born to the two sisters with combined variants, four had hypercalcemia and five had hypoglycemia as neonates. In these mothers, calcium levels slowly normalized postpartum. In the affected neonates, calcium and blood glucose levels became normal within weeks.ConclusionCombined variants of CYP24A1 caused long-standing gestational hypercalcemia and late-onset hypertension. In neonates, elevated serum calcium and hypoglycemia can be consequences necessitating prompt measures. CYP24A1 mutations should be considered in unexplained gestational hypercalcemia. Their combined effects during pregnancy have not been observed previously.

Background: The prescription of liothyronine (LT3) to treat hypothyroidism is increasing worldwide; however, the long-term safety of LT3 use has yet to be determined. Previous studies have suggested a possible association between LT3 use and breast cancer. The aim of this study was to examine the effects of LT3 use on cancer incidence and mortality. Methods: Our sample included the full adult population of individuals living in Sweden with at least three purchases of thyroid hormone therapy between July 2005 and December 2017. Individual-level data on drug purchases were linked to registry data on cancer incidence and mortality. There were 575,461 individuals with at least three purchases, of which 11,147 had made at least three purchases of LT3, including combinations of levothyroxine (LT4) and LT3. Individuals were followed for a median follow-up time of 8.1 years. We applied Cox regression with a time-varying exposure variable, comparing LT3 users (individuals with at least three cumulative purchases of LT3) with LT4-only users (the rest). Outcomes included breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, and breast cancer mortality. We adjusted for age, sex, previous thyroid cancer, previous other cancer, use of antithyroid preparations, use of sex hormones, and dose in multivariate analyses. Results: Multivariate analyses produced a hazard ratio of 0.93 (95% confidence interval [0.75-1.15]) for breast cancer incidence (only females), 0.97 (0.87-1.08) for any cancer incidence, 0.69 (0.61-0.77) for all-cause mortality, 0.78 (0.62-0.98) for any cancer mortality, and 0.91 (0.50-1.66) for breast cancer mortality (only females). Conclusions: In this large, Swedish, long-term registry-based study, the use of LT3 did not lead to increased breast cancer incidence, any cancer incidence, all-cause mortality, any cancer mortality, or breast cancer mortality compared with LT4 use. Somewhat surprisingly, there was evidence of lower mortality in LT3 users in models adjusting for dose, potentially an artifact of underlying associations between dose and health status/diagnosis.