Decrease In Glycemia Research Articles

Lipids and glycemia profiles in adults: the Italian Health Examination Survey 2023 - CUORE Project

Abstract Background WHO recommends monitoring glycemic and lipid profiles in the population to control and prevent NCDs. The target for glycemic/diabetes is to halt the rise within 2025 (2010 as baseline). The Italian Ministry of Health (MoH) has strengthened prevention/health promotion and supported their periodic assessment through national health examination surveys (HESs), financed by MoH-CCM and conducted within the CUORE Project. Methods In 2023 a new HES started including the assessment of fasting serum glycemia, total and HDL cholesterolemia and triglyceridemia. Up to now, data from random samples of residents in 7 Regions (of 20 regions) distributed in North, Centre and South of Italy and aged 35-74 years are available (687 men, 704 women). Glycemia and lipids profiles were assayed by a central lab. Elevated glycemia/diabetes (DM): glycemia ≥ 126 mg/dl and/or on medication. Elevated total cholesterol/hypercholesterolemia (HChol): total cholesterol ≥ 240 mg/dl and/or on medication. Results Glycemia mean level was 97 mg/dl (95%CI: 95-99) in men and 90 mg/dl (89-91) in women; DM resulted 10% (5-14) and 8% (4-12) respectively. Among those with DM, about 2 in 10 men and 1 in 10 women were unaware; about 2 and 3 of 10 were aware but not on medication, respectively. Total cholesterol mean level was 192 mg/dl (189-195) in men and 200 (197-202) in women; HChol resulted 24% (18-31) and 29% (22-36) respectively. Mean level of HDL cholesterol was 48 mg/dl (48-49) in men and 59 mg/dl (58-60) in women; mean level of triglycerides was 121 mg/dl (115-126) and 95 mg/dl (92-98) respectively. Among those with HChol, about 1 in 10 men and 2 in 10 women were unaware; about 2 of 10 were aware but not on medication. Conclusions Compared to 2008, these preliminary data showed a significant decrease of glycemia, total cholesterol and triglycerides means values both in men and women, as well as of DM and HChol prevalence, but improvements on their awareness and control are still necessary. Key messages • In the Italian adult general population significant improvements in lipids and glycemia profiles occurred compared to 15 years ago. • The implementation of periodic health examination surveys is important for estimating indicators based on objective measurements and for estimating awareness and control of risk conditions.

Metabolic profile and glycemic response in fully-grown sows born using assisted reproductive technologies

The aim of the present work was to gain insight into the metabolism of pigs derived from assisted reproductive technologies during their adulthood. Approximately 4h after feeding, a blood sample was taken from 3.5 year old sows born by artificial insemination (AI group, n = 7) and transfer of in vitro produced embryos (IVP group, n = 11) to determine the physiological concentrations of the main biomarkers of carbohydrates (glucose and lactate), proteins (albumin, creatinine and urea) and lipids (cholesterol and triglycerides). Four weeks later, an oral glucose tolerance test (OGTT; 1.75g glucose/kg body weight) was performed after an overnight fast and 1h of water withdrawal. Blood samples were obtained prior (T = 0 min; fasting conditions) and 15, 30, 45, 60, 90, 120, 150, 180, 210 and 240 min after glucose intake. At each time point, glycemia was measured immediately using glucometer test strips, and serum was collected to determine the above metabolites along with insulin and glucagon. After OGTT, the area under the curve (AUC) between sampling times and homeostasis model assessment of insulin resistance (HOMA) indices were calculated. Under physiological conditions, the concentration of metabolites studied was similar between AI and IVP sows. In both groups, fasting decreased cholesterol and increased triglycerides and urea (P < 0.001). However, creatinine and lactate were similar in both groups under physiological and fasting conditions. The expected increase in albuminemia and decrease in glycaemia after fasting was only observed in IVP sows. OGTT revealed a different glucose curve pattern (monophasic in AI and biphasic in IVP group), a lower mean concentration of cholesterol, glucose, lactate, triglycerides in IVP compared to AI pigs (P < 0.01), and a higher mean concentration of albumin, creatinine and insulin in IVP compared to AI group (P < 0.05). On the contrary, no differences were found between groups for mean serum glucagon and urea levels, nor for glucose homeostasis indices HOMA-IR and HOMA-%B. The AUC differed between groups at several time points with larger AUC for creatinine, and smaller AUC for glucose, glucagon, and triglycerides, in IVP pigs than in AI pigs at 180–210 min (P < 0.05). In conclusion, under physiological conditions the metabolic profile of fully-grown AI and IVP sows is similar and within normal ranges. Glucose challenge revealed differences in metabolic and insulin responses between groups but with normal glucose tolerance in both cases.

#1762 Reduction in intradialytic glycemia and increased oxygen consumption as potential indicators of intradialytic parenchymal stress

Abstract Background and Aims Patients undergoing chronic hemodialysis (HD) face heightened all-cause and cardiovascular mortality due to various risk factors, with intradialytic stress playing a fundamental role. Recently, the assessment of intradialytic oxygen trends has emerged as a potential parameter for evaluating parenchymal stress. Specifically, an intradialytic increase in the oxygen extraction ratio (OER), derived from the ratio of peripherical oxygen saturation to central venous oxygen saturation, identifies patients at a greater risk of intradialytic events and increased clinical risk. In addition to OER, intradialytic consumption of glucose indicates higher tissue metabolic demand, likely indicative of parenchymal stress. We hypothesize that OER and intradialytic glucose consumption may be phenomena related to increased intradialytic parenchymal stress and, therefore, may be correlated. This study aimed to assess the potential correlation between intradialytic glycemia trends and oxygen extraction (OER). Method Patients in chronic HD treatment with a central venous catheter (CVC) for HD were enrolled from January 2019 to January 2020. The exclusion criteria were: ongoing acute pathology, diabetes mellitus, and undergoing hemodialysis for less than six months. OER and glycemia were measured during three consecutive HD sessions at baseline, 15, 30, 60, and 120 minutes into treatment, and post-HD. For statistical analysis, average values for each patient across the three dialysis sessions were considered. Results Twenty patients with a permanent CVC (10 males, 10 females; age 74 ± 13 years; HD vintage 46 ± 34 months) were enrolled. The pre-HD mean OER in the initial three HD sessions was 34 ± 7, increasing to 46 ± 9 post-HD, with a mean percentage delta OER of 39 ± 20%. Evaluating OER trends in the entire population revealed an increase in OER (∆OER) from the first 15 minutes of treatment (∆OER% 15’: 14 ± 7; ∆OER% 30’: 18 ± 22, p &amp;lt; 0.01). Patients' baseline glycemia was 120 ± 31 mg/dl at the start of the HD session and 111 ± 21 at the end, with a delta of −11 ± 21 mg/dl and a glucose delta percentage of 4%. Patients with higher oxygen consumption after 15 and 30 minutes of treatment experienced a greater decrease in glycemia. Specifically, ∆OER at 15’ negatively correlated with glycemia values at 15’ (r: −0.494, p &amp;lt; 0.05), 30’ (r: −0.521, p &amp;lt; 0.05), 60’ (r: −0.644, p &amp;lt; 0.01, Fig. 1), and 120’ (r: −0.714, p &amp;lt; 0.01), and post-HD (r: −0.634, p &amp;lt; 0.05). Patients were then divided based on the magnitude of mean O2 consumption measured post-HD into two groups: ΔOER ≤ mean and ΔOER &amp;gt; mean (threshold 40%). Patients with a higher ∆OER showed a more significant decrease in glycemia from the first 15 minutes of HD, confirmed at the end of HD (ΔOER ≤ 40%: Δglucose post-HD −2 ± 40; ΔOER &amp;gt; 40%: −22 ± 28, p &amp;lt; 0.05, Fig. 2). Conclusion The data confirm that oxygen extraction during hemodialysis progressively increases from the first 30 minutes of treatment. Changes in OER are associated with a reduction in glycemia, particularly patients with higher ΔOER have a more pronounced decrease in glycemia. This association between OER and glycemia supports the hypothesis that these two parameters are linked to the same pathophysiological phenomenon, such as increased intradialytic cellular metabolic activity. Studies with larger populations will help confirm this association and propose glycemia delta as an indicator of intradialytic parenchymal stress.

Effects of Regular Exercise on the Biochemical, Oxidative, and Inflammatory Profiles and Quality of Life in Older Spaniards with Metabolic Syndrome.

Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55-70 years; living in the Balearic Islands, Spain) were divided into two groups (n = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.

Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats.

In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin-angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT1 R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT1 R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT1 R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal-associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO-AT1 R signalling in the control of refeeding-induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.

ОСОБЕННОСТИ ФАКТОРОВ РИСКА РАЗВИТИЯ КАРДИОВАСКУЛЯРНЫХ ОСЛОЖНЕНИЙ ПРИ ОЖИРЕНИИ У ДЕТЕЙ

Introduction. The most common risk factors for the development of cardiovascular diseases are hypertension and obesity, which are formed in childhood, however, the most significant clinical and metabolic markers of cardiovascular risk have not yet been identified in pediatric practice. Aim. To study the characteristics and interrelations of cardiovascular risk factors in obese children and adolescents for planning correction at the stage of functional changes. Material and methods. The study included 141 obese children – 69 boys and 72 girls (in whom the degree of standard deviation of the body mass index was 2.88 [2.75; 3.41] and 2.93 [2.59; 4.05], respectively) and 78 healthy children (40 boys and 38 girls), comparable by sex and age. Results and discussion. In the examined children, there is an insufficient decrease in blood pressure at night from both systolic blood pressure and diastolic blood pressure, in the absence of clinically and statistically significant deviations in single measurements. The triglyceride-glucose index and the N-terminal inactive peptide of natriuretic hormone demonstrated high concentrations in normoglycemia and the absence of dyslipidemia. Against the background of obesity, trimethylaminoxide concentrations were lower than in healthy children. Conclusion. In order to timely correct blood pressure, it is necessary to use daily monitoring in obese children, even against the background of the absence of signs of arterial hypertension with single measurements. Even against the background of lean normoglycemia in obese children and adolescents, it is advisable to diagnose the formation of insulin resistance and hyperinsulinemia using indicators of insulin levels, calculation of the HOMA-IR index, triglyceride-glucose index. Correction of blood pressure variability is possible with changes in certain parameters of body composition (decrease in fat mass and increase in muscle mass) and hormonal and metabolic parameters (decrease in glycemia, very low-density lipoproteins, insulin and increase in high-density lipoproteins). The level of trimethylaminoxide showed lower rates of obesity in children compared to healthy peers, which differs from the literature data on the adult population and limits its use as a biomarker for the development of cardiovascular complications in obesity in children

Six-month periodic fasting does not affect somatosensory nerve function in type 2 diabetes patients.

Current strategies for preventing diabetic sensorimotor polyneuropathy (DSPN) are limited mainly to glucose control but rapid decrease of glycemia can lead to acute onset or worsening of DSPN. The aim of this study was to examine the effects of periodic fasting on somatosensory nerve function in patients with type 2 diabetes (T2D). Somatosensory nerve function was assessed in thirty-one patients with T2D (HbA1c 7.8 ± 1.3% [61.4 ± 14.3 mmol/mol]) before and after a six-month fasting-mimicking diet (FMD; n=14) or a control Mediterranean diet (M-diet; n=17). Neuropathy disability score (NDS), neuropathy symptoms score (NSS), nerve conduction velocity and quantitative sensory testing (QST) were analyzed. 6 participants of the M-Diet group and 7 of the FMD group underwent diffusion-weighted high-resolution magnetic resonance neurography (MRN) of the right leg before and after the diet intervention. Clinical neuropathy scores did not differ between study groups at baseline (64% in the M-Diet group and 47% in the FMD group had DSPN) and no change was found after intervention. The differences in sensory NCV and sensory nerve action potential (SNAP) of sural nerve were comparable between study groups. Motor NCV of tibial nerve decreased by 12% in the M-Diet group (P=0.04), but did not change in the FMD group (P=0.39). Compound motor action potential (CMAP) of tibial nerve did not change in M-Diet group (P=0.8) and increased in the FMD group by 18% (P=0.02). Motor NCV and CMAP of peroneal nerve remained unchanged in both groups. In QST M-diet-group showed a decrease by 45% in heat pain threshold (P=0.02), FMD group showed no change (P=0.50). Changes in thermal detection, mechanical detection and mechanical pain did not differ between groups. MRN analysis showed stable fascicular nerve lesions irrespective of the degree of structural pathology. Fractional anisotropy and T2-time did not change in both study groups, while a correlation with the clinical degree of DSPN could be confirmed for both. Our study shows that six-month periodic fasting was safe in preserving nerve function and had no detrimental effects on somatosensory nerve function in T2D patients. https://drks.de/search/en/trial/DRKS00014287, identifier DRKS00014287.

Mechanisms of renoprotective action of sodium-glucose cotransporter-2 inhibitors (gliflozins): a clinician’s view

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a group of drugs that block the enzyme responsible for the reabsorption of glucose and sodium in the proximal part of the nephron. They appeared in clinical practice about a decade ago for the treatment of type 2 diabetes mellitus, but the first clinical studies showed the potential of these agents in preventing cardiovascular and renal events. Among the main mechanisms of the renoprotective effect of SGLT2i, the following are distinguished now: 1)reduction of hyperfiltration/pressure in the glomerulus (narrowing of the afferent and dilation of the efferent arterioles); 2) metabolic shift towards the use of free fatty acids for obtaining energy (increasing energy efficiency and reducing lipotoxic damage to cells); 3) antihypoxic effect (direct— due to a decrease in oxygen needs and indirect— due to an increase in hemoglobin); 4) reduction of pressure and fluid overload; 5) anti-inflammatory and antifibrotic effects; 6)other effects (decrease in glycaemia, body weight, uric acid level, etc.). Presumably, SGLT2i administration causes a universal cellular reaction (autophagic flux), which leads to improved energy efficiency, reduces cellular stress and increases the resistance of cells to overload. The significance of various mechanisms in the formation of the overall effect differs depending on the main cause of kidney damage, concomitant pathology, metabolic characteristics of the patient, degree of kidney ischemia, etc. It is different not only in each individual patient, but, probably, in the same patient at different stages of the disease. However, the implementation of these mechanisms allows preventing the development/progression of kidney failure and prolonging the life of patients.

Efekat zdravstveno vaspitne intervencije u formi savetovanja na promene antropometrijskih i biohemijskih parametara obolelih od dijabetes melitusa tip 2

Introduction: Diabetes is a significant public health problem. In Serbia, 12% of the population suffers dominantly from type 2 diabetes, the development of which is associated with an inadequate diet and lack of physical activity. The treatment of patients involves the application of diet therapy in combination with medical treatment. The aim of this paper is to evaluate the differences in anthropometric and biochemical parameters in patients with type 2 diabetes after the counseling work. Respondents and methods: The research was conducted as a retrospective evaluation study through the analysis of medical records of users of the Nutrition Counseling Service of the Public Health Institute of Subotica. The sample included 34 patients with type 2 diabetes, mostly women (71%). Results: The average body weight of the patients was 87.6 kg, waist circumference 105 cm, the average glycemima was 7.14 mmol/l, and the blood pressure level was 140/84 mmHg. After counseling, at the first control measurement 2-4 months after the first examination, the patients lost an average of 3 kg, the waist circumference decreased by an average of 2 cm, and the percentage of fat in the body decreased by 1.6%. There was a decrease in glycemia by 0.6 mmol/l and systolic blood pressure by 5 mmHg. Although the second control examination was attended by a much smaller number of patients, based on the results, it was observed that the average values of the observed parameters were significantly lower compared to the initial values (body mass decreased by 1 kg, waist circumference by 4 cm, glycemia level by an additional 1 mmol/l). Conclusion: Based on the results of the research, it can be concluded that after the counseling work, there was a significant improvement in the nutritional status and glycemia in patients with type 2 diabetes.

INFLUENCE OF KETOSIS AND GLYCEMIA LEVELS ON CRAVING FOR ETHANOL IN ALCOHOLIZED RATS

Relevance. In case of developed alcoholic disease, under conditions of alcoholic hypoglycemia, ketone bodies act as an energy substrate for the brain. However, the role of ketone hunger for maintaining the craving for alcohol has not been established. The assumption of such a connection has a right to exist, since it is alcohol that stimulates the formation of ketone bodies. Therefore, with developed alcoholism, the desire to consume alcohol (and, in fact, "saturate" the brain with ketone bodies) can be considered as a consequence of hypoketonemia. Accordingly, the hunger of the alcoholic is the result of hypoketonemia, but not hypoglycemia. Therefore, it is relevant to conduct a study in which the given variables (controlled by us) were the level of glycemia and the level of ketonemia, and the amount of alcohol consumed voluntarily (under conditions of free choice) was a derivative and dependent value.&#x0D; Objective: to study the relationship between craving for alcohol, and levels of glycemia and ketonemia in alcoholized rats.&#x0D; Materials and methods. Male white rats (n = 40) were forcibly alcoholized with 10% ethanol in 16 weeks. After that, for 30 days, they had a free choice of three types of drinking: clean water, 5% glucose, and 10% ethanol. The volume of consumed liquids was recorded. The criterion for the developed alcohol dependence was the preference of ethanol. At this stage, the animals were divided into 4 groups. Rats were injected per os with 0.8-1.5 ml of: 1.4% unitiol (3.5 mg / kg) to suppress ketonemia – group 1 (n = 10); 40% starch (1.0 g / kg) to eliminate hypoglycemia – group 2 (n = 10); 2.8% unitiol and 80% starch to suppress ketonemia and eliminate hypoglycemia – group 3 (n = 10); 0.9% NaCl as a control – group 4 (n = 10). Blood glucose (from the tail vein) and urine ketone bodies were monitored. The glucose level was determined with a glucometer. Test strips were used to detect ketone bodies in urine. The results were processed with MedStat software. To measure the strength of the correlation between the indicators, Spearman and Pearson tests were used.&#x0D; Results. No ketone bodies were found in the urine of healthy animals; however, after the end of forced alcoholization, varying levels of ketonuria were recorded in all rats: from 0.5 to 10 mmol / L (Spearman's rank correlation test was 0.8). Glycemia in healthy rats was 7.0 ± 1.4 mmol / L. After alcoholization, it decreased (p &lt;0.001) to 3.0 ± 0.7 mmol / l. Ethanol consumption during first 10 days of forced alcoholization was 3.2 ± 0.7 ml per 100 g of animal weight; by the end of the third week - 4.9 ± 1.1 ml; by the end of the sixth week - 6.4 ± 1.4 ml (this was a climax of consumption, since consumption did not increase up to the 16th week).&#x0D; After a 30-day correction, the level of glycemia (mmol / L) was as follows: animals of the 1st group (unitiol) - 4.0 ± 0.8; animals of the 2nd group (enhanced carbohydrate diet) - 7.1 ± 1.2; animals of the 3rd group (unitiol + enhanced carbohydrate diet) - 7.1 ± 1.1; animals of the 4th group (0.9% NaCl) - 3.5 ± 0.8.&#x0D; Alcohol consumption (ml per 100 g of animal weight) after 30-day correction was as follows: in group 1 (unitiol) - 5.1 ± 0.9; in group 2 (enhanced carbohydrate diet) - 2.7 ± 1; in group 3 (unitiol + enhanced carbohydrate diet) - 3.5 ± 1.5; in group 4 (0.9% NaCl) - 4.5 ± 1.2.&#x0D; A positive strong correlation was found between ethanol consumption and a decrease in glycemia (Pearson's test – 0.8).&#x0D; Conclusion. In alcoholized animals with severe hypoglycemia and ketosis, drug suppression of ketosis does not reduce the craving for ethanol. Metabolic correction, aimed at eliminating hypoglycemia, helps to reduce alcohol consumption and reduce the severity of ketosis. The reason for maintaining a stable craving for alcohol is the metabolic demand of the brain for ketone bodies, as alternative food sources in conditions of alcoholic hypoglycemia, and the synthesis of which is stimulated by alcohol intake.

Antihyperglycemic and Antidyslipidemic Activities of the Aqueous Salvia hispanica Extract in Diabetic Rat.

The study targeted to evaluate the antihyperglycemic activity of Salvia hispanica. Salvia hispanica L. (Lamiaceae) is a medicinal plant with many beneficial properties on human health. This objective of the study was to investigate the antihyperglycemic effect of the aqueous extract of Salvia hispanica (S. hispanica) seeds and its capacity to improve lipid profile in normal and STZ-induced diabetic rats. The seed aqueous extract of S. hispanica (SHSAE) at a dose of 100 mg/kg was administered orally in normal and diabetic rats. The effect of oral SHSAE treatment on blood glucose and lipid levels during 15 days was assessed in normal and streptozotocin-induced diabetic rats. The oral glucose tolerance test (OGTT) was carried out. The antioxidant activity of SHSAE was also examined. The decrease of glycemia in rats following the administration of the plant extract suggested that the studied extract possesses antidiabetic effect. The extract of S. hispanica produced hypolipidemic effect with a significant lowering effect on plasma total cholesterol levels and increased on HDL-cholesterol levels. SHSAE was also able to enhance glucose tolerance using OGTT. Moreover, SHSAE possesses a potential antioxidant effect in vitro. In conclusion, this study demonstrates the antihyperglycemic and antilipidemic effects of SHSAE in rats.

Antihyperglycemic Activity of Aqueous Extract of Euphorbia guyoniana in Streptozotocin-Induced Diabetic Rats.

This work assessed the antihyperglycemic effect of Euphorbia guyoniana. Euphorbia guyoniana (Boss. and Reut.) is widely used in traditional medicine. This study was designed to confirm this traditional use by assessing its antihyperglycemic capacity in vivo. The effect of the aqueous extract of Euphorbia guyoniana (Boss. and Reut.) (60 mg/kg) on glycemia in both normal and diabetic rats was evaluated. The glycogen content in the liver and skeletal muscles (extensor digitorum longus and soleus) was measured. Furthermore, liver histopathological analysis was performed. The findings showed that Euphorbia guyoniana (Boss. and Reut.) exhibited a significant decrease in glycaemia in diabetic rats (from 20±2 mmol/l to 5.5 mmol/l after 6 hours of oral administration; p<0.0001 and from 20±2 mmol/l to 4.5 mmol/l after 7 days of once-daily repeated oral administration of the aqueous Euphorbia guyoniana extract; p<0.0001). In addition, the extract increased the glycogen content in the liver (41±4 mg/g versus 70±5 mg/g in normal and diabetic rats respectively) and extensor digitorum longus (39±4 mg/g versus 60±1 mg/g in normal and diabetic rats, respectively), and partially restored corporal weight in diabetic rats. Furthermore, this aqueous extract has been shown to suppress hyperglycemia induced by glucose load in treated diabetic rats. Additionally, hepatic histology in diabetic rats has been improved. This plant revealed the presence of several phytochemical constituents and possessed antioxidant activity. The current study evidenced that Euphorbia guyoniana (Boss. and Reut.) has a beneficial effect on improving hyperglycemia and glycogen depletion in the diabetic state.

Abstract 13936: Cardiac Beta3-Adrenergic Receptors Increase Pentose Phosphate Pathway Flux And Protect Against Hypertrophic Remodeling By Reducing Oxidative Stress

Introduction: Cardiac beta3-adrenergic receptors (β3AR) mediate effects opposite to those of β1AR and β2AR and are upregulated during the development of hypertrophy or heart failure (HF). We previously showed that upon hemodynamic or neurohormonal stress β3AR confer protection against cardiac fibrosis and hypertrophic remodeling, two key components of the progression towards HF. Hypothesis: We tested the hypothesis that modulations of cardiac metabolism are implicated in the myocardial protection by β3AR Results: In a transgenic mouse model with cardiac-specific expression of the human β3AR (TG; compared to their wild-type littermates (WT)) myocardial glucose uptake is enhanced both in vivo ( 18 Fluoro-deoxy-glucose by PET-CT) and in isolated adult cardiac myocytes exposed to hemodynamic stress by transverse aortic constriction for 9 weeks (TAC). In addition, a decrease in glycaemia during insulin tolerance test as well as an increase in Glut4 transporter in TG post-TAC suggest an insulin-dependency, as well as sensitization underlying the accrued glucose entry. Targeted metabolomics on cardiac tissue from TG (vs. WT) revealed a significant increase of several intermediates of the pentose phosphate pathway (PPP) post-TAC. Transcriptional expression from isolated cardiac myocytes showed an upregulation of several key enzymes of the pathway, that correlate with an elevation of NADPH levels, a major product of the PPP, with no modifications in nucleotides levels, implying a re-entry via the lower glycolysis. Consistent with an upregulated PPP, we found an increase in the ratio of reduced-to-oxidized Glutathione and a decrease in several indicators of oxidative stress (ROS production, MetO) both indicating a reduced oxidative stress. Conclusion: β3AR mediate an increased flux through the PPP, sustained by an enhanced glucose uptake, in cardiac myocytes upon prolonged hemodynamic stress. The associated renewal of the NADPH pool and cellular detoxification of ROS may contribute to the protective role of β3AR against hypertrophic remodeling. As β3AR agonists are currently used in clinical practice for urological indications, these original cardiac protective mechanisms may offer immediate perspectives for the prevention or treatment of HF.

Hydropinotherapy with Sulphurous Mineral Water as Complementary Treatment to Improve Glucose Metabolism, Oxidative Status, and Quality of Life.

Hydropinotherapy is a salus per aquam (Spa) treatment suitable as a complementary approach to treat several diseases, which strongly affect the quality of life (QoL). Hydropinotherapy with sulphurous mineral water exerts benefits thanks to components, such as hydrogen sulphide, which is considered mainly responsible for antioxidant and hypoglycaemic effects. Such properties, linked from each other, could favour an improvement in patients’ QoL. However, data on humans are scarce. This study aimed to investigate whether a cycle of sulphurous hydropinotherapy was able to modify plasma levels of glucose and reactive oxygen metabolites (ROMs) and improve QoL in patients suffering from several chronic disorders. A prospective, observational study involved patients with gastrointestinal diseases who received a prescription of a cycle of sulphurous hydropinotherapy (S-HT). Age- and sex-matched control group was enrolled (No S-HT). Glycaemia and plasma concentration of ROMs were measured in all subjects. The impact of spa treatment on the QoL was assessed using the Short Form 36 Health Status Survey questionnaire (SF-36). All parameters were measured at baseline and at the end of a 2-week treatment. Between the groups, no differences were found in glycaemia and ROMs at baseline. In the S-HT group, a reduction in glycaemia and ROMs, both in respect to baseline (p = 0.005 and p = 0.031, respectively) and to control group, as shown by the delta value calculated, as the difference between the values at 2 weeks and baseline (p = 0.0009 and p = 0.0001, respectively). In the S-HT, delta ROMs was the best predictor of delta glycaemia with a direct linear correlation (beta = 0.559, 95% CI 0.471 to 0.647, p < 0.0001). In the S-HT, the SF-36 total score was improved both when compared with baseline (p = 0.002) and with No S-HT (p = 0.001). Sulphurous hydropinotherapy induces a decrease in glycaemia and ROM levels, also ameliorating the patients’ QoL. Therefore, it could be considered a useful complementary therapeutic approach.

Нюанси інсулінотерапії при лікуванні діабетичного кетоацидозу

Актуальність. Чітка програма інсулінотерапії є запорукою ефективного лікування пацієнта в стані діабетичного кетоацидозу (ДКА). Підходи до лікування змінювались разом із накопиченням досвіду, проте і зараз думки фахівців стосовно дози та методики проведення інсулінотерапії неоднозначні. Мета дослідження: оцінка ефективності використання інсулінотерапії шляхом постійної інфузії шприцевим насосом в стартовій дозі 0,1 ОД/кг/год під контролем глікемії без використання внутрішньовенної болюсної дози інсуліну та визначення необхідної добової дози інсуліну в першу добу лікування ДКА. Матеріали та методи. Обстежені 55 хворих із ДКА віком від 9 до 65 років. Середній вік хворих становив 31,58 ± 17,18 року, частка пацієнтів жіночої статі серед досліджуваних становила 56 %, чоловічої — 44 %. Пацієнти з цукровим діабетом 1-го типу становили 80 %. Визначення рівня глюкози проводилось у свіжій капілярній крові автоматичним аналізатором глюкози, всім контролювали глікемію через годину після введення 0,1 ОД/кг/год інсуліну та в подальшому проводили корекцію дози за потребою під контролем рівня глюкози. При лікуванні використовували інсуліни короткої дії та аналоги інсулінів ультракороткої дії, підраховували їх сумарну дозу за першу добу лікування. Результати. Рівень глікемії при госпіталізації перебував в межах від 6,7 до 62,2 ммоль/л, у середньому — 23,37 ± 10,16 ммоль/л. Серед досліджуваних глікемія до 13 ммоль/л траплялася у 13 % хворих. Глікемія від 13 до 20 ммоль/л була у 29 % хворих, а гіперглікемія понад 20 ммоль/л — у 58 %. Динаміка рівня глікемії через годину після введення вирахуваної дози інсуліну у 63,6 % хворих була бажаною, зниження глікемії за годину становило 0,5–5,3 ммоль/л, проте відзначалася індивідуальна чутливість до введеної дози інсуліну. Добова доза інсуліну становила від 0,5 до 5,83 ОД/кг. Медіана добової дози інсуліну серед досліджуваних становила 1,36 ОД/кг, найчастіше — 0,92–1,88 ОД/кг за добу [25 %; 75 %]. Висновки. Доза інсуліну в розрахунку 0,1 ОД/кг/год є дієвою, проте через встановлену індивідуальну чутливість до інсуліну вагомим чинником ефективності лікування є контроль глікемії щогодини для своєчасної корекції дози інсуліну.

Possibilities of application a fixed combination of alogliptin and pioglitazone for type 2 diabetes mellitus treatment

Hyperglycemia in T2DM is based on three main mechanisms: insulin resistance, progressive β-cell dysfunction, and excess glucose production by the liver.The onset of T2DM is usually preceded by a long period of insulin resistance. Prescribing sugar drugs that affect different links of pathogenesis, reducing a steady decrease in glycemia. To date, in clinical practice, various combinations of hypoglycemic drugs are used, the choice of which is determined by the characteristics of the course of diabetes in the patient, the presence of concomitant diseases and complications of diabetes, as well as the dominant clinical problem. This resolution provides an expert council opinion on the feasibility of using a combination of alogliptin and pioglitazone in patients with type 2 diabetes.

D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: a pilot study

BackgroundAndrogen deficiency affects men in the adulthood, causing several harmful effects at the reproductive and behavioural levels. Since aromatase is an enzyme that catalyses the conversion of androgens to estrogens, and it is responsible for an adequate balance of both sex hormones in males and females, the administration of molecules acting as down modulators may contribute to restore an abnormal enzymatic activity. A prospective pilot study was carried out to investigate the effect of D-chiro-inositol, a putative aromatase down-modulator, on serum levels of testosterone, estradiol, estrone, dehydroepiandrosterone and epiandrosterone from a group of adult male volunteers. Glucose, insulin, follicle-stimulating hormone, luteinizing hormone, inhibin B, D-chiro-inositol and myo-inositol serum levels were also measured.ResultsMale volunteers were selected according to age and body mass index. Subjects with altered glycemia and/or hormonal status, due to advanced age or abnormal weight, were enrolled in the study. Each of the 10 volunteers enrolled took oral D-chiro-inositol (1 g/day) for 1 month. Serum assays of selected markers were performed at baseline (control) and after treatment. D-chiro-inositol administration was associated to reduced serum levels of estrone (− 85.0%) and estradiol (− 14.4%), and increased serum levels of testosterone (+ 23.4%) and dehydroepiandrosterone (+ 13.8%). In addition, epiandrosterone levels were higher (+39%) after treatment. On the other hand, follicle-stimulating hormone, luteinizing hormone and inhibin B did not change. A trend toward a decrease of glycemia, insulinemia and Homeostatic Model Assessment index was observed after D-chiro-inositol treatment, although differences did not reach statistical significance. D-chiro-inositol treatment did not cause any noticeable adverse effect.ConclusionsIncreased androgens and decreased estrogens seem to confirm that D-chiro-inositol acts as an aromatase down-modulator, but with a still unknown mechanism of action. This pilot study opens up new perspectives of research and therapeutic applications for D-chiro-inositol at different dosages and length of treatment.Authorization number 005/2020 released by the Local Ethics Committee of Alma Res Fertility Center, Rome.Trial registration numberNCT04615767 (registry: ClinicalTrials.gov)Date of registration: November 3, 2020

ОЦЕНКА ВЛИЯНИЯ ТЕРАПИИ ИНКРЕТИНОМИМЕТИКАМИ И ГЛИФЛОЗИНАМИ НА ФУНКЦИЮ АЛЬФА И БЕТА-КЛЕТОК ПОДЖЕЛУДОЧНОЙ ЖЕЛЕЗЫ У ПАЦИЕНТОВ С СД 2 ТИПА

Defect in the function of pancreatic cells is one of the key pathophysiological factors in type 2 diabetes, in particular, an imbalance between the secretion of insulin and glucagon, as well as a decrease in the efficiency of converting proinsulin into insulin, often observed. The aim of the work was to compare the characteristics of the secretory function of pancreatic alpha and beta cells in 43 patients with decompensated type 2 diabetes mellitus when using new classes of anti-diabetic drugs: glucagon-like peptide receptors agonists (GLP1ra) and inhibitors of the sodium-glucose transporter-2 (SGLT2i). Long-term treatment with these drugs (for 12 months) contributed to the normalization of the HbA1c level and a decrease in the % of visceral fat, as well as a decrease in the glucagon level compared to the baseline level. In both groups of patients, subgroups with high and low proinsulin levels have been identified. Under the influence of GLP1ra therapy, in patients of the low proinsulin subgroup, serum concentration of proinsulin and C-peptide significantly decreased, indicating a decrease in insulin secretion and a possible reduce in adaptive release of proinsulin as a result of glycemia decrease. Among patients treated with SGLT-2i, high pre-treatment proinsulin levels associated with higher glucagon and C-peptide concentrations comparing the low proinsulin subgroup. After 12 months of treatment, no significant changes in the concentration of glucagon, C-peptide and proinsulin were observed in both subgroups of patients treated with SGLT2i.

The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy-A Review.

Background. Diabetes mellitus (DM) is a non-infectious pandemic of the modern world; it is estimated that in 2045 it will affect 10% of the world’s population. As the prevalence of diabetes increases, the problem of its complications, including diabetic retinopathy (DR), grows. DR is a highly specific neurovascular complication of diabetes that occurs in more than one third of DM patients and accounts for 80% of complete vision loss cases in the diabetic population. We are currently witnessing many groundbreaking studies on new pharmacological and surgical methods of treating diabetes. Aim. The aim of the study is to assess the safety of pharmacological and surgical treatment of DM in patients with DR. Material and methods. An analysis of the data on diabetes treatment methods currently available in the world literature and their impact on the occurrence and progression of DR. Results. A rapid decrease in glycaemia leads to an increased occurrence and progression of DR. Its greatest risk accompanies insulin therapy and sulfonylurea therapy. The lowest risk of DR occurs with the use of SGLT2 inhibitors; the use of DPP-4 inhibitors and GLP-1 analogues is also safe. Patients undergoing pancreatic islet transplants or bariatric surgeries require intensive monitoring of the state of the eye, both in the perioperative and postoperative period. Conclusions. It is of utmost importance to individualize therapy in diabetic patients, in order to gradually achieve treatment goals with the use of safe methods and minimize the risk of development and progression of DR.

Antihypernociceptive and Neuroprotective Effects of the Aqueous and Methanol Stem-Bark Extracts of Nauclea pobeguinii (Rubiaceae) on STZ-Induced Diabetic Neuropathic Pain.

The greatest common and devastating complication of diabetes is painful neuropathy that can cause hyperalgesia and allodynia. It can disturb psychosocial functioning by increasing levels of anxiety and depression. This work was designed to evaluate the antihyperalgesic, antidepressant, and anxiolytic-like effects of the aqueous and methanol extracts of Nauclea pobeguinii stem-bark in diabetic neuropathy induced by streptozotocin in mice. Diabetic neuropathy was induced in mice by the intraperitoneal administration of 200 mg/kg streptozotocin (STZ) to provoke hyperglycemia. Nauclea pobeguinii aqueous and methanol extracts at the doses of 150 and 300 mg/kg were administered by oral route, and their effects were evaluated on antihyperalgesic activity (Von Frey filaments, hot plate, acetone, and formalin tests), blood glucose levels, body weight, serum, sciatic nerve proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and sciatic nerve growth factor (IGF and NGF) rates, depression (open field test, forced swimming test, tail suspension test), and anxiety (elevated plus maze, light-dark box test, social interaction). Oral administration of Nauclea pobeguinii stem-bark aqueous and methanol extracts (150 and 300 mg/kg) produced antihyperalgesic, antidepressant, and anxiolytic-like effects in STZ-induced diabetic neuropathic mice. Extracts also triggered a decrease in glycaemia and increased body weight in treated animals. They also significantly (p <0.001) reduced tumour necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6 and significantly (p <0.001) increased nerve growth factor (NGF) and insulin-like growth factor (IGF) in sciatic nerves. The results of this study confirmed that Nauclea pobeguinii aqueous and methanol extracts possess antihyperalgesic, antidepressant, and anxiolytic activities and could be beneficial therapeutic agents.