Cardioprotective Effects of Sodium-Glucose Cotransporter 2 Inhibitors and Their Possible Association With Normalization of the Circadian Index of Heart Rhythm.

BACKGROUND: Updated recommendations for the treatment of heart failure with reduced ejection fraction (HFrEF) include sodium-glucose cotransporter 2 (SGLT2) inhibitors and other long-established HFrEF therapies. These drugs' mechanisms of action have yet to be fully clarified. OBJECTIVE: This study evaluated the effects of SGLT2 inhibitors on the modulation of autonomic function at 1 month beyond conventional HF therapy. METHODS: This single-center, observational, prospective study was conducted from January 2020 to December 2022. Patients with type 2 diabetes who had ischemic HFrEF and met the study criteria were considered for SGLT2 inhibitor treatment with empagliflozin or dapagliflozin. Changes in the circadian index were used as the primary outcome to assess the early effects of SGLT2 inhibitors on autonomic function. Changes in functional effort capacity and laboratory findings were also evaluated. Participants' circadian index was measured by a 24-hour rhythm Holter monitoring recorder (BTL-08 Holter H100). A symptom-limited treadmill test assessed patients' effort capacities. Tests were repeated after 1 month of therapy. RESULTS: The mean (SD) age of the 151 participants was 56.95 (7.29) years; their mean (SD) left ventricular EF was 35.69% (7.10%), and 95 participants were men (62.9%). From baseline to 1 month, mean (SD) daytime heart rate (80.63 [9.17] vs 77.67 [8.04] beats per minute; P = .004) and nighttime heart rate (76.83 [11.34] vs 73.81 [10.25] beats per minute; P = .03) decreased significantly. Variation in the circadian indexes (mean [SD], 1.04 [0.02] vs 1.10 [0.04]; P < .001) was statistically significant, favoring increased modulation of autonomic function. The increases in exercise duration (mean [SD], 8.88 [3.69] minutes and median [IQR], 8.81 [5.76-12.13] minutes vs 9.72 [3.14] and 9.59 [7.24-12.22] minutes; P = .04) and exercise capacity (mean [SD], 203.38 [65.18] m and median [IQR], 119.22 [149.43-259.15] m vs 335.61 [51.39] and 325.79 [293.59-376.91] m; P < .001] were also significant. CONCLUSION: The use of SGLT2 inhibitors during early treatment can favorably affect both autonomic dysfunction and functional effort capacity of patients with type 2 diabetes with ischemic HFrEF.

The effect of diabetes mellitus on disease prognosis in COVID-19 patients.

BACKGROUND: In this study, we aimed to evaluate and compare the clinical characteristics, laboratory findings, and outcomes of hospitalized patients with and without diabetes along with poorly vs. well-controlled diabetes. METHODS: A total of 341 hospitalized patients with COVID-19 confirmed by RT-PCR and/or chest imaging suggestive of COVID-19 infection were retrospectively included in this study. The patients were divided into 2 groups as diabetic (n = 120) and non-diabetic (n = 221). Demographic data, symptoms, comorbidities, and laboratory values were recorded. The patients were classified according to the clinical stages defined by guidance of the WHO for COVID-19. The percentage of patients with severe disease was higher in diabetic group (n = 57) 47.5% compared to non-diabetic group (n = 61) 27.8% (p = 0.001). The percentage of patients requiring oxygen therapy was significantly higher in 61 (51.2%) diabetic group than non-diabetic group 65 (29.4%) (p = 0.001). The median duration of hospitalization in the diabetic group was 8 days [IQR 6-11.5] that was significantly higher than the non-diabetic group as 7 days [IQR 5-10] (p = 0.009). The median duration of hospitalization in poorly controlled diabetic group was 9 days [IQR 6.00-16.00] that was significantly higher than well-controlled diabetic group 8 days [IQR 6.00-11.00] (p = 0.006). RESULTS: Patients with diabetes were more susceptible to COVID-19 infection and the infection was more severe in patients with diabetes compared to patients without diabetes. However, the mortality rate was similar between diabetic and non-diabetic group. Diabetic COVID-19 patients without other comorbidities were not prone to severe infection. CONCLUSION: Patients with diabetes and comorbidities, apart from the glycemic control, should receive intensive monitoring and disease management.

Insulin resistance in nodular thyroid disease.

BACKGROUND: Insulin had been shown to have a mitogenic effect on thyroid cell cultures. The aim of this study was to investigate insulin resistance in patients with euthyroid nodular goiter. METHODS: Sixty-three patients with nodular thyroid disease and 83 healthy controls were included in the study. Both the patient and the control group were euthyroid, euglycemic and normotensive. None of the study subjects had risk factors for insulin resistance. All the study subjects were evaluated by serum insulin levels and biochemical parameters and thyroid ultrasound. All subjects with thyroid nodules greater than 1cm (n = 36) were offered to undergo thyroid fine needle aspiration biopsy. RESULTS: The two groups were similar with respect to age, gender, BMI, waist circumference, serum lipid levels, serum fT3, fT4 and TSH levels. But HOMA was found to be significantly higher in the patient group (p: 0.007) and thyroid volume was significantly greater in the patient group (p = 0.03). In the patient group there was a significant correlation between HOMA and nodule volume (p < 0.001) while there was not a significant correlation between HOMA and number of thyroid nodules. Thyroid cancer was diagnosed in 3 of the 36 patients (8.33 %). CONCLUSIONS: Insulin resistance may induce increased thyroid proliferation and nodule volume and nodule formation. Therefore, insulin resistance may be a risk factor for euthyoid nodular goiter.

Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism.

OBJECTIVE: In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT). SUBJECTS AND METHODS: The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid. RESULTS: Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041). CONCLUSIONS: Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.

Clinical management, psychosocial characteristics, and quality of life in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis in Turkey: Results of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening inherited disease leading to early-onset atherosclerosis and associated morbidity. Because of its rarity, longitudinal data on the management of HoFH in the real world are lacking, particularly on the impact the condition has on quality of life (QoL), including the impact of the extracorporeal lipid removal procedure apheresis (LA). METHODS: The A-HIT1 study included 88 patients with HoFH aged ≥12 years receiving regular LA in 19 centers in Turkey. Demographic and disease characteristics data were obtained. For patients aged ≥18 years, additional data on psychosocial status were obtained via the SF-36 score, the Hospital Anxiety and Depression Scale, and a HoFH-specific questionnaire. RESULTS: There was no standardized approach to therapy between centers. Mean (±SD) frequency of LA sessions was every 19.9 (±14) days, with only 11.6% receiving LA weekly, and 85% of patients were not willing to increase LA frequency. The most common concerns of patients were disease prognosis (31%), and physical, aesthetic, and psychological problems (27.5%, 15.9%, and 11.6%, respectively). Lower age at diagnosis was associated with better QoL, lower anxiety, improved functioning, and greater emotional well-being compared to later diagnosis. CONCLUSIONS: These findings demonstrate that adult patients with HoFH undergoing LA, experience significant impairment of QoL with an increased risk of depression. From patients' point of view, LA is time-consuming, uncomfortable, and difficult to cope with. The speed of diagnosis and referral has a considerable impact on patient well-being.

A nation-wide survey of patients with homozygous familial hypercholesterolemia phenotype undergoing LDL-apheresis in Turkey (A-HIT 1 registry).

BACKGROUND AND AIMS: Homozygous familial hypercholesterolemia (HoFH) is a genetic condition characterized by lethally high levels of low-density lipoprotein cholesterol (LDL-C) from birth, and requires rapid and aggressive intervention to prevent death due to coronary heart disease and/or atherosclerosis. Where available, lipoprotein apheresis (LA) is the mainstay of treatment to promote survival. METHODS: A-HIT1 registry was conducted with the aim of providing insight to the real-life management of HoFH patients undergoing LA in Turkey, where LA procedures are fully reimbursed and widely available. Participating centers provided patient information, including family history, treatment patterns and relevant laboratory values, via a standard questionnaire. RESULTS: The study evaluated 88 patients (mean age: 27 ±â€¯11 years, 41 women) in 19 centers. All patients were receiving regular LA with a clinical diagnosis of HoFH. Mean age at first symptom disease was 10 ±â€¯10 years, and at diagnosis it was 12 ±â€¯11 years; 74.7% were diagnosed before age 15 years; and only 31% before the age of 7. First referral of most patients was to pediatricians. Early onset coronary artery disease was present in 57.8% of patients. Mean age at first LA was 21 ±â€¯12 years. Only 11 (12.5%) patients were undergoing LA weekly. Mean frequency of apheresis sessions was 19 ±â€¯13 days. For the last four LA sessions, LDL-C levels reached the target in only in 5.7% of patients. CONCLUSIONS: Diagnosis of HoFH is delayed, and LDL targets are not reached. LA frequencies are not optimal. Urgent attention is needed to support the survival of patients with HoFH.

Serum irisin and apelin levels and markers of atherosclerosis in patients with subclinical hypothyroidism

ABSTRACT Objective: In this study, we aimed to evaluate serum irisin and apelin levels in patients with subclinical hypothyroidism (SCH) when they were subclinical hypothyroid and become euthyroid after levothyroxine therapy and association of these adipokines with markers of atherosclerosis such as serum homocysteine levels and carotid intima-media thickness (IMT). Subjects and methods: The study included 160 patients with newly diagnosed subclinical hypothyroidism due to Hashimoto's thyroiditis and 86 euthyroid healty subjects. Serum glucose and lipid profile, insulin, HOMA, TSH, free T3, free T4, anti-thyroperoxidase and anti-thyroglobulin antibodies, homocysteine, apelin and irisin levels were measured in all study subjects. Thyroid and carotid ultrasound examinations were performed. The subclinical hypothyroid group was reevaluated after 12-weeks of levothyroxine therapy when they became euthyroid. Results: Clinical characteristics of the patient and control group were similar. Glucose, insulin and HOMA levels, lipid parameters and free T3 were similar between the two groups.. Serum homocystein was higher and apelin was lower in patients with SCH, but irisin levels were similar between the two groups. While thyroid volume was lower, carotid IMT was significantly greater in patients with SCH (pCarotidIMT:0,01). After 12-weeks of levothyroxine therapy, all the studied parameters remained unchanged except, serum freeT4, TSH, homocystein and apelin. While homocystein decreased (p: 0,001), apelin increased significantly (p = 0,049). In multivariate analysis, low apelin levels significantly contributed to carotid IMT (p = 0,041). Conclusions: Apelin-APJ system may play a role in vascular and cardiac dysfunction in patients with SCH and treatment of this condition may improve the risk of cardiovascular disease.

Clomiphene citrate-induced severe hypertriglyceridemia.

OBJECTIVE: To report a case of severe hypertriglyceridemia associated with clomiphene citrate (CC) treatment. DESIGN: Case report. SETTING: A patient referred to an endocrinology clinic of a state hospital. PATIENT(S): A 29-year-old, overweight woman with a history of polycystic ovary syndrome who had been given clomiphene citrate (CC) for ovulation induction and presented with severe hypertriglyceridemia. She had a family history of type 2 diabetes and hyperlipidemia. INTERVENTION(S): Clomiphene citrate treatment was discontinued, and gemfibrozil treatment at a dose of 1,200 mg/d was started. MAIN OUTCOME MEASURE(S): Serum lipid levels. RESULT(S): With the discontinuation of CC treatment and start of a specific lipid-lowering agent, the patient's lipid profile improved. After 3 months, CC therapy was restarted, and again severe hypertriglyceridemia developed, which resolved with the previous treatment strategies. CONCLUSION(S): Clomiphene citrate should be used cautiously in women having risk factors for dyslipidemia, and, even in the presence of a normal lipid profile, lipid levels should be closely monitored when CC treatment is instituted.