Diabetes mellitus type two is one of the major cardiovascular risk factors. Treatment of diabetes can reduce this risk, but the treatment options differ a lot in their risk-reducing capabilities. We ...compared the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), arterial stiffness and lipid parameters - in insulin naive patients with DMT2.
To 23 individuals who previously had uncontrolled DMT2 on two or more oral antidiabetic drugs, IGlar-300 and IDeg-100 were applied for 12 weeks and then switched in a cross over design manner. Prior and after of each insulin phase, we analysed biochemical parameters,7-point SMBG profile over three days and arterial stiffness which was assessed indirectly by measuring the augmentation index (AIx) on the principles of applanation tonometry.
There were no significant differences between IGlar-300 and IDeg-100 regarding reduction of mean glucose values and coefficient of variation (CV). Both insulins insignificantly reduced AIx for standardised pulse of 75 beats/min and without differences between them. IGlar-300 and IDeg-100 reduced triglycerides and increased HDL with no significant difference between the two insulins. IGlar-300 increased the total cholesterol level and IDeg-100 decreased total cholesterol, but without statistically significant difference. IGlar-300 increased LDL level by 0.508 mmol/L and IDeg-100 decreased LDL by 0.217 mmol/L, with statistically significant difference (p = 0.0215).
This study did not show significant difference between IGlar-300 and IDeg-100 regarding glycaemic parameters and augmentation index using the same dose of 0.2 IU/kg for both insulins, but it has revealed possible differences in impact on lipid profile.
Clinicaltrials.gov, NCT04692415 . Retrospectively registered on December 31th 2020.
Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-),
-mutated locally advanced or ...metastatic breast cancer following disease progression on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting approximately 60% of treated patients, and sometimes necessitating dose reductions, treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia and timely intervention have a key role in achieving optimal glycemic control and maintaining alpelisib dose intensity to optimize the benefit of this drug. A glycemic support program implemented by an endocrinology-oncology collaborative team may be very useful in this regard. Lifestyle modifications, mainly comprising a reduced-carbohydrate diet, and a designated stepwise, personalized antihyperglycemic regimen, based on metformin, sodium-glucose co-transporter 2 inhibitors, and pioglitazone, are the main tools required to address the insulin-resistant hyperglycemia induced by alpelisib. In this report, based on the consensus of 14 oncologists and seven endocrinologists, we provide guidance for hyperglycemia management strategies before, during, and after alpelisib therapy for HR+, HER2-,
-mutated breast cancer, with a focus on a proactive, multidisciplinary approach.
To compare the effectiveness of different titration algorithms for insulin glargine U100 used in everyday practice to achieve glycaemic targets in patients with type 2 diabetes mellitus (T2DM).
A ...total of 526 patients (278 in Slovenia, 248 in Croatia) with T2DM (aged ≥ 18 years) and treated with insulin glargine prior to inclusion were enrolled. Patients self-titrated insulin glargine according to physicians’ guidance.
Among the 524 patients included in the final analysis, the titration algorithm from the LANMET study was used most commonly (n = 368, 70.5% patients), followed by the Treat-To-Target (TTT) algorithm (n = 117, 22.4%). At the end of the study (6 months), 179 (34.3%) patients reached HbA1c ≤ 7%. There was no significant difference in the proportion of patients who reached their target HbA1c between the different algorithms at 6 months (35.6% using LANMET, 30.7% with TTT, and 32.4% with other algorithms; p = 0.611). HbA1c levels were more significantly reduced in patients using the TTT algorithm compared to LANMET (−2.31%, vs. −1.57%; p < 0.05). The proportion of patients with reported symptomatic hypoglycaemia did not differ significantly between the algorithms.
Continuous titration of insulin glargine U100 is a safe and efficient option for T2DM management, regardless of the titration algorithm applied.
Background
There is an ongoing discussion about possible differences between insulin degludec (IDeg-100) and glargine U300 (IGlar-300). There is little data and head-to-head comparison of IDeg-100 ...and IGlar-300 regarding their simultaneous impact on glycemic variability and oxidative stress in patients with type 2 diabetes mellitus (T2DM).
Objective
In our randomized, open-label, crossover study, we compared the impact of IDeg-100 and IGlar-300 on glycemic variability and oxidative stress in insulin-naive patients with T2DM.
Methods
We recruited a total of 25 adult patients with T2DM (7 females) whose diabetes was uncontrolled (HbA1c ≥7.5%) on two or more oral glucose-lowering drugs; a total of 22 completed the study. Mean age was 57.3 (SD 6.99) years and duration of diabetes was 9.94 (SD 5.01) years. After the washout period, they were randomized alternately to first receive either IDeg-100 or IGlar-300 along with metformin. Each insulin was administered for 12 weeks and then switched. At the beginning and end of each phase, biochemical and oxidative stress parameters were analyzed. On 3 consecutive days prior to each control point, patients performed a 7-point self-monitoring of blood glucose profile. Oxidative stress was assessed by measuring thiol groups and hydroperoxides (determination of reactive oxygen metabolites test) in serum.
Results
IGlar-300 reduced mean glucose by 0.02-0.13 mmol/L, and IDeg-100 reduced glucose by 0.10-0.16 mmol/L, with no significant difference. The reduction of the coefficient of glucose variation also did not show a statistically significant difference. IGlar-300 increased thiols by 0.08 µmol/L and IDeg-100 increased thiols by 0.15 µmol/L, with no significant difference (P=.07) between them. IGlar-300 reduced hydroperoxides by 0.040 CARR U and IDeg-100 increased hydroperoxides by 0.034 CARR U, but the difference was not significant (P=.12).
Conclusions
The results of our study do not show a significant difference regarding glycemic variability between patients receiving either insulin IDeg-100 or IGlar-300, although IGlar-300 showed greater dispersion of data. No significant difference in oxidative stress was observed. In a larger study, doses of insulins should be higher to achieve significant impact on glycemic parameters and consequently on glycemic variability and oxidative stress.
Trial Registration
ClinicalTrials.gov, NCT04692415; https://clinicaltrials.gov/ct2/show/NCT04692415
We present the case of a 48-year-old male patient who underwent surgery for a recurrent metastatic parathyroid gland carcinoma in the patient's right paratracheal space of the neck. The patient had ...undergone surgery for lower right parathyroid gland carcinoma 28 months earlier.
The metastases were resected
with an ipsilateral central neck dissection and with the removal of the enlarged lower left parathyroid gland. After exploration of the remnant parathyroid glands we noticed that lower left parathyroid gland was macroscopically enlarged so we decided to remove it to prevent possible hypercalcemia in future and to also prevent possible recurrence of cancer or development of a new primary, considering the identical embryological origin of the lower parathyroid glands and possibility of synchronous, multiple tumors, which generally follow the same embryological origin if they occur. The patient was also treated with radiation therapy after the surgery.
With the present surgical approach to recurrent metastatic parathyroid gland carcinoma, we aimed to prevent the recurrence of cancer or development of new primary and prevent or delay hypercalcemia in the future with all severe adverse metabolic states associated with high serum calcium levels.
The primary objective of the study was to evaluate the correlation between prostaglandin F2-alpha and tumour necrosis factor-alpha concentration and that of pain experienced by patients undergoing ...thermal balloon ablation. Furthermore we evaluated the correlation between the endometrial and myometrial thicknesses and the degree of pain experienced by patients undergoing the procedure, and in addition the correlation between PGF2-alpha, TNF-alpha and endometrial and myometrial thicknesses. Single-arm cohort study (Canadian Task force classification II-2). In University Medical Centre Ljubljana, outpatient setting, 40 perimenopausal women with dysfunctional uterine bleeding (DUB), underwent endometrial thermal balloon ablation. The thickness of the endometrium and myometrium was measured prior to surgery using a transvaginal ultrasound that provided cross-sectional images. The degree of pain was rated using the visual analogue scale (VAS) and numeric rating scale (NRS) immediately and 60 minutes after the procedure. The concentration of PGF2-alpha and TNF-alpha in venous blood was measured prior to, at the end of and 60 minutes after the procedure. The results showed a positive correlation between the concentration of PGF2-alpha released during endometrial ablation and the endometrial and myometrial thickness (p > 0.01), including the reported degree of pain (p > 0.01). The concentration of TNF-alpha indicates a positive correlation with the level of pain (p > 0.05), but is not dependent on the thicknesses of the endometrium and myometrium. Endometrial thickness correlates to the degree of pain and the prostaglandin F2-alpha concentration. In clinical practice, performing the Gynecare ThermaChoice procedure immediately after menstruation or preoperative preparation of the endometrium using oral contraceptives enables this procedure to be performed in outpatient settings and can be considered a valuable treatment option for DUB.
Gap junctions (GJs) are important in the regulation of cell growth, morphology, differentiation and migration. However, recently, more attention has been paid to their role in the pathogenesis of ...different diseases as well as tumorigenesis, invasion and metastases. The expression pattern and possible role of connexins (Cxs), as major GJ proteins, under both physiological and pathological conditions in the adrenal gland, were evaluated in this review. The databases Web of Science, PubMed and Scopus were searched. Studies were evaluated if they provided data regarding the connexin expression pattern in the adrenal gland, despite current knowledge of this topic not being widely investigated. Connexin expression in the adrenal gland differs according to different parts of the gland and depends on ACTH release. Cx43 is the most studied connexin expressed in the adrenal gland cortex. In addition, Cx26, Cx32 and Cx50 were also investigated in the human adrenal gland. Cx50 as the most widespread connexin, along with Cx26, Cx29, Cx32, Cx36 and Cx43, has been expressed in the adrenal medulla with distinct cellular distribution. Considerable effort has recently been directed toward connexins as therapeutically targeted molecules. At present, there exist several viable strategies in the development of potential connexin-based therapeutics. The differential and hormone-dependent distribution of gap junctions within adrenal glands, the relatively large gap junction within this gland and the increase in the gap junction size and number following hormonal treatment would indicate that gap junctions play a pivotal role in cell functioning in the adrenal gland.
With the rising global burden of inflammatory bowel disease (IBD) and the rising costs of novel biological drugs, there is an increasing need for dietary approaches and functional foods that could ...modulate the course of IBD. The Mediterranean diet has proven to be efficacious in managing chronic inflammatory diseases, and recent studies have also shown its benefits in the setting of IBD. Since olive oil and its compounds have been shown to provide a considerable anti-inflammatory effect, in this review, we aim to discuss the latest evidence concerning the impact of olive oil and its bioactive compounds on IBD. Numerous preclinical studies have exhibited solid evidence on the mechanisms by which polyphenol-rich extra-virgin olive oil (EVOO) or specific polyphenols like hydroxytyrosol (HT) provide their anti-inflammatory, antioxidative, antitumour, and microbiota-modulation effects. Accordingly, several human studies that explored the effects of olive oil on patients with IBD further confirmed the evidence brought forward by preclinical studies. Nevertheless, there is a need for larger-scale, multicentric, randomized control trials that would finally elucidate olive oil's level of efficacy in modulating the course of IBD.
Abstract
Introduction: Clinical course of COVID-19 infection is diverse and the best therapeutical guidelines are still lacking. Case Presentation: We present a case of 73 year old male COVID-19 ...positive patient. In 2017 transnasal hypophysectomy was performed due to prolactinoma. He receives therapy (hydrocortisone 20 + 10 mg/day, levothyroxine 75/50 µg/day, bromocriptine 2.5 mg twice/day). He suffers also from arterial hypertension. Present illness started with intensive dry cough, fever (37.5◦C), diarrhoea and loss of smell. On the first day patient was febrile up to 38.4◦C and later afebrile. Laboratory parameters showed abnormalities in several parameters: D-dimers 13.45 (RR:< 0.50) mg/L, creatinine 110 (49-90) µmol/L, ALT 73 (12-28) U/L, LDH 531 (25-241) U/L, creatine kinase 549 (<177) U/L, GGT 277 (9-35) U/L, CRP 38 (<5 mg/L), sedimentation rate 40 (5-28) mm/3.6ks, procalcitonine 0.07 (<0.05) ng/ml, sodium 128 (137-146) mmol/L, hs-TroponinT 18 (< 14) ng/L, neutrophils 8.56 (2.06-6.49 x109/L), lymphocytes 0.52 (1.19-3.35 x109/L) and pO2 6.1 (11.0-14.4) kPa. At the admission X-ray showed normal presentation, while four days later on the right side pneumonia was noticed as spotty inhomogeneous shading. He was treated with azithromycin, hydrocortisone (50 mg twice/day) and oxygen supplementation. At the beginning of hospitalization he was addicted to O2 10-12 L/min. After 22 days of hospitalization he was discharged without any symptom but with still positive SARS-CoV2 swabs. After a 30 days of follow-up, his swabs are now negative with no laboratory abnormalities. In the meantime, his two brothers, born in 1945 and 1940 died due to COVID-19 infection. They did not receive substitutional corticosteroid therapy. Conclusion: The main pathophysiological mechanism of infection is explained by cytokine storm. Hypercytokinemia causes myelosuppression and vascular endothelium damage. Corticosteroids are potent anti-inflammatory agents. High-doses of corticosteroids might beneficially modulate the host immune response to SARS-CoV2 virus and have protective role in this patient.
Although metabolic syndrome was not extensively studied in type 1 diabetes, higher insulin resistance, the core feature of the syndrome was found to be associated with increased risk of developing ...microvascular complications. As diabetic nephropathy may progress to advanced lesion before microalbuminuria appears, we investigated the association of the metabolic syndrome and estimated glucose disposal rate (eGDR) with urinary albumin excretion (UAE), retinopathy and neuropathy in normoalbuminuric type 1 diabetic patients. Two hundred and 98 patients (UAE < 30 mg / 24 h at three occasions) were divided according to the IDF metabolic syndrome; eGDR (mg kg(-1) min(-1)) was calculated: 24.31-(12.22 x WHR) - (3.29 x HT) - (0.57 x HbA1c), (WHR = waist-to-hip ratio, HT = hypertension). Patients with (n = 99) compared to those without metabolic syndrome (N = 199) showed higher UAE (15.96 +/- 9.10; 13.48 +/- 8.36 mg /24 h), C-reactive protein (2.39 +/- 4.09;1.12 +/- 2.03 mg/L), prevalence of retinopathy (70.7; 55.27%) and polyneuropathy (80.8; 68.3%), and lower eGDR (5.75 +/- 1.74; 8.96 +/- 1.9), (p > 0.05). In patients with high-normal UAE, retinopathy and polyneuropathy eGDR was significantly lower compared with patients with low-normal UAE, and without retinopathy and polyneuropathy. In multiple regression analysis UAE and retinopathy were associated with diabetes duration (beta = -0.20, beta = -0.62), eGDR (beta = - 0.106; beta = -0.041), metabolic syndrome (beta = 0.49, beta = 0.28), (p > 0.05). In type 1 diabetic patients insulin resistance and IDF defined metabolic syndrome are associated with high-normal UAE, retinopathy and polyneuropathy. The predictive value of the metabolic syndrome for development of microalbuminuria and retinopathy needs to be assessed in further follow-up studies.
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