Preuranjena ovarijska insuficijencija (POI) podrazumijeva prekid ovarijske funkcije prije 40. godine života. Bolest se prezentira amenorejom, hipergonadotropnim hipogonadizmom i neplodnošću. S ovom ...dijagnozom žene reproduktivne dobi teško se suočavaju. Klinička slika u ovih bolesnica je vrlo raznolika, isto kao i mogući uzroci. POI je povezan s ozbiljnim posljedicama za zdravlje, uključujući psihološko opterećenje, osteoporozu, autoimune poremećaje, ishemijsku koronarnu bolest i povećan mortalitet. Liječenje treba započeti odmah kako bi se spriječile dugotrajne posljedice. Nefarmakološke strategije i promjena životnog stila prva su linija liječenja u slučaju smanjene mineralne gustoće kosti (BMD), zajedno sa suplementima kalcija i D vitamina. Hormonsko nadomjesno liječenje (HNL) omogućava uspostavu hormonske ravnoteže i oponaša normalnu funkciju jajnika.
Proinflammatory counterworks are important at different stages of tumor development, particularly during invasion and metastasis. Immune cells and their signal molecules can influence all stages of ...tumor progression, as well as therapeutic intervention. Proinflammatory cytokines are known triggers of growth in gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we explored the immunohistochemical expression of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-2, and IL-6 in tissues from 43 GEP-NEN patients with tumors of gastric, duodenal, ileal, appendical, and colonic origin. The immunohistochemical expression of TNF-α was increased in tumor groups with high proliferation rates (Ki67; p = 0.034), as well as in those with higher tumor grades (p = 0.05). Moreover, the immunohistochemical expression of TNF-α positively correlated with death outcomes (p = 0.016). Expression of IL-6, IL-1β, and IL-2 displayed similar immunohistochemical expression patterns regardless of Ki67, although the expression between the ILs differed. Most GEP-NENs had high levels of IL-6 and lower levels of IL-1β and IL-2. Although further comprehensive studies are required for a complete understanding of activated mechanisms in proinflammatory protumoral microenvironment of GEP-NENs, TNF-α is a potential marker in the prognosis of those tumors.
Subclinical hypothyroidism (SCH) in pregnancy is common, according to literature, affecting up to 15% of pregnancies. It still represents a controversy weather levothyroxine has beneficial effects on ...pregnancy outcomes. In this retrospective and prospective cohort study, we assessed fetal and maternal outcomes in women with known thyroid status pre-pregnancy, and hypothyroidism during pregnancy. We included 393 pregnant women, 90 (22.9%) diagnosed with overt and 303 with SCH (77.1%). A total of 94 (56%) had positive anti-TPO antibodies. Levothyroxine substitution across all observational periods was suboptimal, mostly during first trimester in both groups of patients (85.4%). There was a difference in the number of live births in favor of group with SCH (p = .004). Women with overt hypothyroidism were more likely to develop complications during pregnancy (RR = 1.153, 95%CI = 0.775 − 1.714) and had positive TPO-antibodies more often (p = .022). The only significant association was found between fetal outcomes in women with SCH and positive TPO-antibodies (p = .018), while positive Tg-antibodies did not affect the pregnancy outcomes of women with SCH. Moreover, no correlation was observed between outcomes and adequacy of levothyroxine substitution. These results indicate that TPO-antibody positivity could be the most important factor of pregnancy outcomes independent of the TSH levels or adequacy of levothyroxine therapy.
Introduction
Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are recommended therapy for type 2 diabetes (T2DM) and liraglutide is the most used worldwide. We assessed the glycemic efficacy ...and extra-glycemic effects of liraglutide during 36 months’ follow-up of individuals with poorly regulated T2DM under routine clinical practice and sought to identify the phenotype of treatment responders.
Methods
A total of 207 individuals were included. The primary endpoint was the proportion of participants with HbA1c < 7.0% and/or weight reduction. Secondary endpoints included changes in lipids, blood pressure, fasting c-peptide, and antidiabetic treatment during follow-up of 3 years.
Results
Liraglutide was prescribed to 89.8% of participants already on at least two antidiabetic medications and 18% on insulin. Subject's mean age was 53.28 ± 9.42 years with duration of diabetes 8.29 ± 4.89 years. Baseline HbA1c was 8.5 ± 1.3% and body mass index (BMI) was 39 ± 4.5 kg/m
2
. Reduction of HbA1c was observed in 84.4% of participants, and 89.2% experienced average weight reduction of 5 kg. A composite outcome (reduction of HbA1c with any weight loss) was achieved in 76.2% of patients. After 6 months on liraglutide treatment, 38.1% of participants achieved target HbA1c level < 7%. This effect was maintained for 36 months in 50.8% of subjects. Increase in c-peptide was evident after 24 months (
p
= 0.030). Participants experienced a significant reduction in systolic blood pressure (BP) (
p
= 0.003), while there was no effect on diastolic BP, lipid profile, or liver enzymes. The number of participants treated with sulfonylurea decreased from 60.8% to 17.5%, while the number treated with insulin and sodium-glucose co-transporter-2 (SGLT-2) inhibitor increased (17.6% to 24.6% and 2.5% to 36.8%, respectively). Independent predictors of durability of HbA1c reduction were initial BMI (
p
= 0.004), HbA1c (
p
< 0.001), systolic BP (
p
= 0.007), and cholesterol (
p
= 0.020). Moreover, female gender and shorter duration of diabetes were independent predictors for HbA1c reduction.
Conclusion
Liraglutide shows sustained glycemic and extra-glycemic effects when used for treatment of obese poorly regulated individuals with T2DM.
Within the last several years, frequency of vitamin D testing has multiplied substantially all over the world, since it has been shown to have an important role in many diseases and conditions. Even ...though liquid chromatography - tandem mass spectrometry (LC-MS/MS) has been identified as "gold standard" method for vitamin D measurement, most laboratories still use immunochemistry methods. Besides analytical problems (hydrophobicity, low circulating concentrations, ability to bind to lipids, albumins and vitamin D binding protein, presence of multiple vitamin D metabolites and variable ratios of 25(OH)D
and 25(OH)D
in the blood), vitamin D shows great preanalytical variability, since its concentration is drastically influenced by seasonal changes, exposure to sun, type of clothes or sun block creams. Vitamin D is mostly measured in serum or plasma, but new studies are showing importance of measuring vitamin D in pleural effusions, breast milk, urine, synovial fluid and saliva. Besides the main role in calcium homeostasis and bone metabolism, many studies linked vitamin D deficiency with cancer, cardiovascular diseases, diabetes, fertility and many other conditions. However, even though initial observational studies indicated that supplementation with vitamin D might be beneficial in disease development and progression; first results of well-designed randomized controlled prospective studies did not find differences in frequency of cardiovascular events or invasive cancer between patients taking vitamin D supplementation compared to placebo. In the light of these recent findings, validity of excessive vitamin D testing remains an open question.
The sodium/glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like-1 receptor agonists (GLP-1RA) are antidiabetic agents effective both in hemoglobin A1c (HbA1c) reduction (with a low risk of ...hypoglycemia) and cardiovascular event prevention. In patients with type 2 diabetes, the add-on value of combination therapy of GLP-1RA and an SGLT-2i seems promising.
To investigate whether the efficacy of GLP-1RA and SGLT-2i combination observed in randomized controlled trials translates into therapeutic benefits in the Croatian population during routine clinical practice and follow-up.
We included 200 type 2 diabetes patients with poor glycemic control and analyzed the effects of treatment intensification with (1) GLP-1RA on top of SGLT-2i, (2) SGLT-2i on top of GLP-1RA compared to (3) simultaneous addition of both agents. The primary study endpoint was the proportion of participants with HbA1c < 7.0% and/or 5% bodyweight reduction. Secondary outcomes included changes in fasting plasma glucose (FPG), prandial plasma glucose, low-density lipoprotein cholesterol, estimated glomerular filtration rate (eGFR), and cardiovascular (CV) incidents assessment over a follow-up period of 12 mo.
The majority of patients were over 65-years-old, had diabetes duration for more than 10 years. The initial body mass index was 39.41 ± 5.49 kg/m
and HbA1c 8.32 ± 1.26%. Around half of the patients in all three groups achieved target HbA1c below 7%. A more pronounced decrease in the HbA1c seen with simultaneous SGLT-2i and GLP-1RA therapy was a result of higher baseline HbA1c and not the effect of initiating combination therapy. The number of patients achieving FPG below 7.0 mmol/L was significantly higher in the SGLT-2i group (
= 0.021), and 5% weight loss was dominantly achieved in the simultaneous therapy group (
= 0.044). A composite outcome (reduction of HbA1c below 7% (53 mmol/mol) with 5% weight loss) was achieved in 32.3% of total patients included in the study. Only 18.2% of patients attained composite outcome defined as HbA1c below 7% (53 mmol/mol) with 5% weight loss and low-density lipoprotein cholesterol < 2.5 mmol/L. There were no significant differences between treatment groups. No differences were observed regarding CV incidents or eGFR according to treatment group over a follow-up period.
Combination therapy with GLP-1RA and SGLT-2i is effective in terms of metabolic control, although it remains to be determined whether simultaneous or sequential intensification is better.
Highlights • Resolve a problem of unmet needs for glycemic improvement in primary care setting. • Define the most acceptable second line agent for treatment of T2DM. • Addition of DPP-4 and SU ...resulted in successful glucose control with no side effects. • More aggressive approach needed by primary care physicians with early intensification of therapy using available agents.
Background and Aims: Recent data suggest that co-administration of gastrin and GLP-1 improves glucose homeostasis and increase β-cell mass in a rodent model of diabetes, we hypothesized that higher ...baseline levels of endogenous gastrin prior treatment could be a predictor of beta cell function and glucoregulation in newly diagnosed DMT2 patients.
Patients and Methods: In this cross-sectional study 317 patients (116 males and 201 females) with new onset DMT2 were included. Patients treated with IPPs were excluded. Fasting plasma glucose (FPG), postprandial PG (PPG), HbA1c, fasting insulin, pancreatic B cell function (HOMA-B), insulin resistance index (HOMA-IR), c-peptide, CgA and gastrin levels were measured at the time of diagnosis, and after 6 months of follow-up.
Results: Baseline Hba1c was 7,49±2,09%, average age of patients was 62.53 ±11.33 years. 65.7% of patients were overweight and obese. Parameters of glucoregulation were not significantly correlated with gastrin (all p> 0.05), while there was moderate negative correlation with HOMA-B (HbA1c r=-.58, p<0.01, FPG r=-.62, p<0.01 and PPG r=-.33, p<0.01) and positive correlation with HOMA-IR (HbA1c r=.22, p<0.01, FPG r=.42, p<0.01 and PPG r=.25, p<0.01). After 6 months follow-up there was a significant reduction of HbA1c, FPG and PPG (all p<0.01), a significant decrease in fasting insulin level (p=0.006), while CgA and gastrin level increased (p=0.003 and p<0.001 respectively). In the stepwise regression analysis, only two independent predictors of gastrin and CgA levels emerged PPG (p=0.009) and BMI (p=0.016).
Conclusion: At the time of DMT2 onset there was no association between baseline gastrin levels and parameters of glucoregulation however after 6 months of follow-up increase in gastrin and CgA levels was observed along with the improvement of glycemic control indicating a possible relationship of gastrin levels and amelioration of beta cell function followed by metformin initiation as well as life style changes.
Disclosure
M. Cigrovski Berkovic: None. D. Herman Mahecic: None. I. Bilic-Curcic: None.
Background and Aims: Experimental data demonstrated that activation of GLP-1 and gastrin signaling induces beta cell neogenesis, resulting in a promotion of glucose-induced insulin secretion. In ...addition, treatment with proton pump inhibitors is associated with greater glycemic control in patients with type 2 diabetes (T2DM), particularly in those on insulin- or GLP-1-based therapy. The aim of this study was to assess gastrin as a potential predictor of beta cell function and glucoregulation in newly diagnosed T2DM patients.
Materials and Methods: In this cross sectional study 190 patients (64 males and 126 females) with new onset T2DM were included. Patients treated with IPPs were excluded. Fasting plasma glucose (FPG), postprandial PG, HbA1c, fasting insulin, pancreatic B cell function (HOMA-B), insulin resistance index (HOMA-IR), fasting c-peptide and gastrin levels were measured at the time of diagnosis.
Results: Baseline HbA1c was 7.53±2.08%, average age of patients was 61.8±10.years and body mass index (BMI) was 31.25±5.73 kg/m2. Parameters of glucoregulation were not significantly correlated with gastrin (all p>0.05), while there was moderate negative correlation with HOMA-B (HbA1c, FPG and PPG; p <0.01 for all) and positive correlation with HOMA-IR (HbA1c, FPG and PPG; p<0.01 for all). Patients with higher baseline measures of glucose regulation had lower HOMA-B and higher HIMA-IR as was expected. There was no association between gastrin and HOMA-B (p>0.05) or HOMA-IR. Furthermore, no association was established between c-peptide, insulin levels and gastrin (p>0.05).
Conclusion: Baseline gastrin levels are not sufficient to have a significant effect on glucoregulation or HOMA-B and HOMA-IR in newly diagnosed T2DM, therefore it could be postulated that further stimulation of gastrin secretion (e.g., with IPPs or GLP-1 based therapy) is needed in order to influence beta cell function and glycemic control.
Disclosure
M. Cigrovski Berkovic: None. D. Herman Mahecic: None. I. Bilic-Curcic: None.
We studied the association between leisure time physical activity (LTPA) and glycemic control, body mass index (BMI), and hypoglycemic incidents in type 1 (T1DM) and type 2 diabetes patients (T2DM).
...This is a cross-sectional study of 198 diabetic patients (60 with type 1 diabetes, 138 with type 2 diabetes). LTPA was assessed by a validated 12-month questionnaire. Patients were grouped as sedentary and moderately to vigorously active. Outcome measures were Hemoglobin A1c (HbA1c), BMI, and hypoglycemic episodes.
LTPA effect on the HbA1c reduction was present in diabetes type 1 patients. Patients who were involved in the moderate to vigorous-intensity physical activity had a greater decrease in the HbA1c (p = 0.048) than patients with low physical activity (p = 0.085). Level of LTPA was neither associated with increased number of hypoglycemic episodes, nor BMI. After an average of 4 years of diabetes, the number of patients requiring more than one antidiabetic agent increased, although the observed difference did not correlate with LTPA level.
LTPA has an influence on the regulation of diabetes type 1, and intensification of medical treatment is compensating for the lack of lifestyle change-especially in type 2 diabetics.
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