Critical questions in diabetes management: What are the most compelling challenges and how can we handle them?

Background: The prevalence of diabetes mellitus is growing worldwide, showing almost a 10-fold increase in the last five decades. Despite advances in the understanding of the disease mechanisms, preventive measures, and treatment options, morbidity and mortality remain high. Moreover, the burden of uncontrolled glycemia and associated complications have a significant impact on healthcare costs. To be ready for the future and emerging issues in the management of diabetes and related disorders, a holistic approach is essential for the prevention of the next generations. So many challenges in the management of diabetes exist globally, which differ according to the health infrastructure, and cultural, economic, and sociodemographic status of the nations. Conclusions: In this minireview and commentary on previously unaddressed needs relating to the management of diabetes, we discuss the ubiquitous and most compelling challenges and suggest potential solutions in the care of patients with diabetes

Role of Chemerin in Cardiovascular Diseases

(1) Background: Obesity is closely connected to the pathophysiology of cardiovascular diseases (CVDs). Excess fat accumulation is associated with metabolic malfunctions that disrupt cardiovascular homeostasis by activating inflammatory processes that recruit immune cells to the site of injury and reduce nitric oxide levels, resulting in increased blood pressure, endothelial cell migration, proliferation, and apoptosis. Adipose tissue produces adipokines, such as chemerin, that may alter immune responses, lipid metabolism, vascular homeostasis, and angiogenesis. (2) Methods: We performed PubMed and MEDLINE searches for articles with English abstracts published between 1997 (when the first report on chemerin identification was published) and 2022. The search retrieved original peer-reviewed articles analyzed in the context of the role of chemerin in CVDs, explicitly focusing on the most recent findings published in the past five years. (3) Results: This review summarizes up-to-date findings related to mechanisms of chemerin action, its role in the development and progression of CVDs, and novel strategies for developing chemerin-targeting therapeutic agents for treating CVDs. (4) Conclusions: Extensive evidence points to chemerin's role in vascular inflammation, angiogenesis, and blood pressure modulation, which opens up exciting perspectives for developing chemerin-targeting therapeutic agents for the treatment of CVDs

Atherosclerosis Development and Progression: The Role of Atherogenic Small, Dense LDL

Atherosclerosis is responsible for large cardiovascular mortality in many countries globally. It has been shown over the last decades that the reduction of atherosclerotic progression is a critical factor for preventing future cardiovascular events. Low-density lipoproteins (LDL) have been successfully targeted, and their reduction is one of the key preventing measures in patients with atherosclerotic disease. LDL particles are pivotal for the formation and progression of atherosclerotic plaques; yet, they are quite heterogeneous, and smaller, denser LDL species are the most atherogenic. These particles have greater arterial entry and retention, higher susceptibility to oxidation, as well as reduced affinity for the LDL receptor. Increased proportion of small, dense LDL particles is an integral part of the atherogenic lipoprotein phenotype, the most common form of dyslipidemia associated with insulin resistance. Recent data suggest that both genetic and epigenetic factors might induce expression of this specific lipid pattern. In addition, a typical finding of increased small, dense LDL particles was confirmed in different categories of patients with elevated cardiovascular risk. Small, dense LDL is an independent risk factor for cardiovascular diseases, which emphasizes the clinical importance of both the quality and the quantity of LDL. An effective management of atherosclerotic disease should take into account the presence of small, dense LDL in order to prevent cardiovascular complications

Soluble CD40 Ligand Levels in Otherwise Healthy Subjects With Impaired Fasting Glucose

Unlike diabetes mellitus and impaired glucose tolerance, it is not clear whether the subjects with impaired fasting glucose (IFG) are at increased risk of atherosclerosis and cardiovascular diseases. The CD40-CD40 ligand interaction is involved in the mechanism of atherosclerosis. We investigated whether soluble CD40L (sCD40L) as well as high sensitive C-reactive protein (hsCRP) levels are increased in subjects with IFG having no confounding factors for inflammation or atherosclerosis. Twenty four IFG subjects with no additional disorders and 40 appropriate healthy controls were studied. sCD40L and hsCRP levels in the IFG and control groups were similar. Blood pressures, total and LDL-cholesterol, and triglyceride levels were also similar, whereas HDL-cholesterol was lower and HOMA-IR indexes were higher in the IFG group. Though the sample size was small, the present data show that sCD40L seems not to alter in subjects with IFG suggesting that it might not be an independent risk factor for atherosclerosis

Waist Circumference Cutoff Points to Predict Obesity, Metabolic Syndrome, and Cardiovascular Risk in Turkish Adults

Objective. The waist circumference (WC) cutoff levels defined for the Caucasian people may not be representative for different ethnic groups. We determined sex specific WC cutoff points to predict obesity, metabolic syndrome, and cardiovascular risk in Turkish adults. Design and Methods. The demographic characteristics of 1898 adult males and 2308 nonpregnant females from 24 provinces of 7 different regions of Turkey (mean age 47 ± 14 yrs) were evaluated. Results. The WC levels of 90 cm and 100 cm define overweight and obese males while the levels of 80 cm and 90 cm define overweight and obese females. With these cutoff values, 239 additional males (12.6%) are diagnosed as overweight and 148 additional males (7.8%) as obese. Instead, 120 females (5.1%) are free of being labeled as obese. Conclusions. This is the first nationwide study to show the action levels of WC for overweight and obese Turkish adults. The ideal cutoff levels of WC to predict metabolic syndrome are 90 cm and 80 cm for Turkish adult men and women, respectively. These values are easy to implement and suggested to be used by the physicians dealing with cardiometabolic disorders in Turkey

Wpływ testosteronowej terapii zastępczej na stężenia witaminy D i FGF-23 w hipogonadyzmie wrodzonym

Introduction: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Material and methods: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. Results: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p<0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). Conclusions: The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.  Wstęp: U chorych z hipogonadyzmem występuje zwiększone ryzyko chorób sercowych I metabolicznych oraz osteoporozy. Witamina D i czynnik wzrostu fibroblastów-23 (FGF-23) uczestniczą w regulacji metabolizmu kostnego i czynności śródbłonka. Istnieją doniesienia na temat niskiego stężenia witaminy D w hipogonadyzmie, natomiast brakuje danych dotyczących wpływu testosteronowej terapii zastępczej (TRT) na to stężenie. Autorzy zbadali wpływ TRT na stężenia witaminy D i FGF-23 oraz na czynność śródbłonka i poziom insulinooporności u chorych z hipogonadyzmem. Materiał i metody: Do badania włączono chorych z wrodzonym hipogonadyzmem hipogonadotropowym (CHH) (n = 32, wiek 20,6 ± 1,58 roku). Chorzy otrzymywali TRT w postaci przezskórnej. Przez rozpoczęciem leczenia i po jego zakończeniu u chorych zebrano dane demograficzne, zmierzono stężenia FGF-23, 25(OH)D3 i asymetryczej dimetyloargininy (ADMA) oraz określono wskaźnik insulinooporności HOMA-IR. Wyniki: Po okresie obserwacji trwającym 3,63 ± 1,33 miesiąca stwierdzono istotne zwiększenie stężeń ADMA i FGF-23 (odpowiednio p = 0,03 i p = 0,005), natomiast stężenie 25(OH)D3 i wskaźnik HOMA-IR nie zmieniły się istotnie. Ponadto zaobserwowano u chorych zwiększenie wskaźnika masy ciała i obwodu pasa (p < 0,001 I p = 0,02) oraz istotne zmniejszenie stężenia cholesterol frakcji HDL (p = 0,006). Wnioski: Wyniki badania pokazują, że krótkotrwałe stosowanie TRT u młodych chorych z CHH, uprzednio nieleczonych, powoduje zwiększenie osoczowego stężenia FGF-23 i ADMA, lecz nie wpływa na stężenie witaminy D. Nie jest jasne, czy jest to wczesny efekt działań niepożądanych TRT w tej grupie bardzo młodych pacjentów z CHH. Konieczne są dalsze prospektywne badania w celu ustalenia długookresowego wpływu TRT na chorobowość i śmiertelność w związku z chorobami sercowymi i metabolicznymi w tej szczególnej populacji

Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease

The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3–4 chronic kidney disease who had no history of smoking, cardiovascular events or use of erythropoietin-based agents. Patients with hemoglobin concentrations above the cohort median of 11.6 g/dl were found to have significant reductions in flow-mediated dilatation compared to those below the median. This inverse relationship remained significant after adjustment for potential confounders, including insulin sensitivity, glomerular filtration rate, proteinuria, body mass index, serum urate, etiology of underlying renal disease, treatment with anti-hypertensive drugs, and traditional Framingham risk factors. Given that hemoglobin can act as an important nitric oxide carrier and buffer, our studies suggest that the mechanism by which hemoglobin influences the endothelium-dependent microcirculation requires its nitrosylation; however, more direct studies need to be performed