Fasting Glycemia Research Articles

Testicular volume in 268 children and adolescents followed-up for childhood obesity-a retrospective cross-sectional study.

Prevalence of obesity in childhood has increased over the past few decades. The impact of obesity and of obesity-related metabolic disorders on testicular growth is unknown. To evaluate the impact of obesity, hyperinsulinemia, and insulin resistance on testicular volume (TV) in pre-pubertal (<9 years), peri-pubertal (9-14 years), and post-pubertal (14-16 years) periods. We collected data on TV, age, standard deviation score (SDS) of the body mass index (BMI), insulin, and fasting glycemia in 268 children and adolescents followed-up for weight control. Peri-pubertal boys with normal weight had a significantly higher TV compared to those with overweight or obesity. No difference was found in the other age ranges when data were grouped according to BMI. Pre- and post-pubertal children/adolescents with normal insulin levels had significantly higher TV compared to those with hyperinsulinemia. Peri-pubertal boys with hyperinsulinemia had significantly higher TV compared to those with normal insulin levels. Post-pubertal adolescents with insulin resistance had lower TV and peri-pubertal boys had higher TV compared to those without insulin resistance. No difference was found in pre-puberty. Closer control of the body weight and the associated metabolic alterations in childhood and adolescence may maintain testicular function later in life.

Association of maternal folate and B12 vitamin status with gestational diabetes mellitus: Still an open issue

ObjectivesThere is conflicting evidence about the role of folate and B12in gestational diabetes mellitus (GDM) onset. The association of vitamin status with GDM was therefore revalued, also measuring the B12active form holotranscobalamin. Methods677 women were evaluated at 24–28 weeks of gestation when OGTT was carried out. The ‘one-step’ strategy was employed for GDM diagnosis. Odds ratio (OR) of having GDM was estimated to quantify the association with vitamin levels. Results180 women (26.6%) had GDM. They were older (median, 34.6 vs. 33.3 years, p = 0.019) and had higher body mass index (BMI) (25.8 vs. 24.1 kg/m2, p < 0.001). Multiparous women had lower levels of all evaluated micronutrients, while overweight lowered both folate and total B12, but not holotranscobalamin. Lower total B12(270 vs. 290 ng/L, p = 0.005), but not holotranscobalamin, was observed in GDM, being weakly negatively correlated with fasting glycemia (r = −0.11, p = 0.005) and 1-h OGTT serum insulin (r = −0.09, p = 0.014). At multivariate analysis, age, BMI and multiparity remained the strongest GDM predictors, while total B12(but not holotranscobalamin and folate) showed a slight protective effect (OR = 0.996, p = 0.038). ConclusionsA weak association between total B12 levels and GDM risk was shown, but it was not confirmed when holotranscobalamin was measured.

Latent class analysis to identify childhood predictors of abnormal glycemic status in young adults with cystic fibrosis

AIMSData on the clinical course of patients with cystic fibrosis (CF) from childhood to CF-related diabetes (CFRD) diagnosis in adulthood are limited. We evaluate whether childhood trajectories of parameters of interest in CF are associated with the risk of abnormal glucose tolerance (AGT) in early adulthood. MethodsPediatric and adult data from 108 subjects with CF followed annually were paired. Participants were grouped according to predominant childhood trajectories for weight, height, body mass index, lung function, glycated hemoglobin levels, fasting glycemia, and 2h post-oral glucose tolerance test glucose levels. Multivariable logistic regression was performed to identify parameters that predict glucose tolerance status in adulthood. ResultsUnivariate analyses reveal that the risk of developing an AGT in adulthood is greater in subjects who are homozygous vs. heterozygous for the ΔF508 mutation, have pancreatic insufficiency vs. sufficiency, or have higher fasting glycemia values at 10 years old rising rapidly vs. lower values that are gradually rising until 17 years old. Multivariable logistic regression retains only fasting glycemia as a significant predictor for the occurrence of AGT in adulthood. ConclusionsFasting glycemia may be a clinical marker of interest to better target children with CF at risk of developing an AGT in early adulthood.

Role of Nutrition in the Etiopathogenesis and Prevention of Nonalcoholic Fatty Liver Disease (NAFLD) in a Group of Obese Adults.

Nonalcoholic fatty liver disease (NAFLD) is liver damage characterized by an accumulation of triglycerides in hepatocytes of >5% (due to an alteration of the balance of the lipid metabolism in favour of lipogenesis compared to lipolysis) that is not induced by the consumption of alcohol. The pathology includes simple steatosis and nonalcoholic steatohepatitis, or NASH (steatosis associated with microinflammatory activities), which can evolve in 15% of subjects with hepatic fibrosis to cirrhosis and the development of hepatocellular carcinoma. The aim of this study is to report the role of macro- and micronutrients in the pathogenesis and prevention of NAFLD in obese subjects. A total of 22 obese or overweight patients with hepatic steatosis were monitored periodically, evaluating their eating habits, fasting glycaemia, lipid picture, liver enzymes, anthropometric parameters, nutrition status, liver ultrasound, oxidative stress, and adherence to the Mediterranean diet. A statistical analysis shows a significant positive relationship between total cholesterol and the Mediterranean adequacy index (MAI) (r = -0.57; p = 0.005) and a significant negative relationship between ALT transaminases and the MAI (r = -0.56; p = 0.007). Nutrition and diet are important factors in the pathogenesis and prevention of NAFLD. The dietary model, based on the canons of the Mediterranean diet, prevents and reduces the accumulation of fat in hepatocytes. Therefore, in agreement with other studies in the literature, we can state that a dietary model characterized by foods rich in fibre, carotenoids, polyphenols, ω3 fatty acids, folic acid, and numerous other molecules is inversely correlated with the serum levels of ALT transaminases, an enzyme whose level increases when the liver is damaged and before the most obvious symptoms of organ damage appear.

Early-induced diabetic obese rat MACAPOS 2

BackgroundDiabetes mellitus is a metabolic disease characterized by an abnormally high blood glucose level. Glucose intolerance and insulin resistance are two characteristics that promote the onset and development of type 2 diabetes. The aim of this study was to create a diabetic rat model from obese rat MACAPOS 2.MethodsA group of rats was subjected to a high-fat diet (HFD) compared to a control group (NC) which received a normal diet. After 16 weeks of HFD, Lee index was calculated, obese rats were subjected to an oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). One group of HFD rats (HFDZ) received streptozotocin 22.5 mg/kg (iv). One week later, weight gain, water and food intakes, urine volume and fasting blood glucose levels were evaluated. Animals were also subjected to glucose tolerance and insulin tolerance tests.ResultsAfter 16 weeks of HFD, rats became obese, glucose intolerant and resistant to insulin. The body weight of rats was significantly high (+ 26.23%) compared to normal rats, glycemia remained significantly high (+ 45.46%, P < 0.01) two hours after administration of glucose in high-fat diet rats, water intake and urine volume were comparable to those of NC. In HFD, the streptozotocin injected after one week (HFDZ), amplified glucose intolerance. During ITT, glycemia remained significantly (P < 0.01) high from 15 min; and did not vary during the 60 min of ITT. The fasting glycemia one week after streptozotocin injection was significantly high (288 mg/dL) compared to HFD (114 mg/dL), associated whit a significant (P < 0.01) increase in water intake and 24 h urine volume.ConclusionThese results showed that MACAPOS 2 associated with a low dose of streptozotocin (22.5 mg/dL) early leads to the diabetes in obese albinos Wistar rats and could be a real model to study the type 2 diabetes mellitus.

Postpartum cardiovascular function in patients with hypertensive disorders of pregnancy: a longitudinal study

Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of cardiovascular diseases that are usually mediated by the development of cardiovascular risk factors, such as chronic hypertension, metabolic syndrome or subclinical myocardial dysfunction. Increasing evidence has been showing that little time elapses between the end of pregnancy and the development of these cardiovascular risk factors. To assess the persistence of hypertension and myocardial dysfunction at four months postpartum in a cohort of women with HDP and to compare the echocardiographic parameters between the peripartum and the postpartum period. In a longitudinal prospective study, a cohort of women with preterm or term HDP and an unmatched group of women with term normotensive pregnancy were recruited. Women with pre-existing chronic hypertension (n=29) were included in the HDP cohort. All participants underwent two cardiovascular assessments: the first was conducted either before or within one week of delivery (V1: peripartum assessment), and the second was between three and 12 months following giving birth (V2: postpartum assessment). The cardiovascular evaluation included blood pressure profile, maternal transthoracic echocardiography (left ventricular mass index (LVMI), relative wall thickness (RWT), left atrial volume index (LAVI), E/A, E/e', peak velocity of tricuspid regurgitation (TR), ejection fraction (EF), and LV global longitudinal strain (GLS) and twist) and metabolic assessment (fasting glycemia, insulin, lipid profile and waist measurement). Echocardiographic data were compared between V1 and V2 using paired t-test or McNemar test in HDP and in the control groups. Among 260 patients with pregnancies complicated by HDP and 33 patients with normotensive pregnancies, 219 (84.2%) and 30 (90.9%) attended postpartum follow-up, respectively. Patients were evaluated at a median (IQR) of 124 (103-145) days after delivery. Paired comparisons of echocardiographic findings demonstrated significant improvements in cardiac remodeling rates (left ventricular mass index (g/m2) 63.4±14.4 vs 78.9±16.2, p<0.0001; relative wall thickness 0.35±0.1 vs 0.42±0.1, p<0.0001), most diastolic indices (E/E' 6.3±1.6 vs 7.4±1.9, p<0.0001), ejection fraction (EF<55%: 9 (4.1%) vs 28 (13.0%), p<0.0001) and global longitudinal strain (-17.3±2.6% vs -16.2±2.4%, p<0.0001) in the postpartum period compared to the peripartum. The same improvements in cardiac indices were observed in the normotensive group. However, at the postnatal assessment, 153/219 (69.9%) had either hypertension (76/219, 34.7%) or an abnormal global longitudinal strain (125/219, 57.1%), 13/67 (19.4%) had metabolic syndrome and 18/67 (26.9%) exhibited insulin resistance. Although persistent postpartum cardiovascular impairment was evident in a substantial proportion of these patients since more than two-thirds had either hypertension or myocardial dysfunction postpartum, cardiac modifications due to pregnancy-related overload and hypertension were significantly more pronounced in the peripartum than in the postpartum periods.

Abstract PD8-02: Metformin (MET) for the prevention of Alpelisib (ALP)-related Hyperglycemia (HG) in PIK3CA-mutated, Hormone Receptor-Positive (HR[+]) HER2-Negative (HER2[-]) Advanced Breast Cancer (ABC): The METALLICA study

Abstract Background: HG is an on-target AE of PI3K inhibition, reported in 63.7% (36.6% G≥3) of HR[+]/HER2[-] ABC patients (pts) treated with ALP plus fulvestrant in SOLAR-1. HG was the most frequent adverse event (AE) leading to ALP discontinuation (6.3%). MET reduces systemic insulin resistance and suppress PI3K and Ras signaling. METALLICA is assessing the prophylactic use of MET for prevention of ALP-induced G3-4 HG in PIK3CA-mutated, HR[+]/HER2[-] ABC pts with normal fasting glycemia or prediabetic criteria. Methods: This is an open-label, single-arm, two-cohort, phase 2 trial. Pts aged ≥18 years, ECOG PS of 0–1, and PIK3CA-mutated, HR[+]/HER2[-] ABC, progressing to an aromatase inhibitor (AI)-containing regimen, ≤2 previous endocrine therapy (ET) and ≤1 prior chemotherapy regimens for ABC were eligible. Pts were enrolled into cohorts according to glycemia at baseline: (A) pts with normal fasting glycemia &amp;lt; 100 mg/dL and glycosylated hemoglobin (HbA1c) &amp;lt; 5.7%; (B) pts with prediabetic fasting glycaemia 100–140 mg/dL and/or HbA1c 5.7–6.4%. Pts received oral ALP 300 mg/day, starting from C1D8, in combination with ET; fulvestrant, letrozole, or exemestane as per standard of care; and oral MET 1000 mg/day on days 1-3 and 2000 mg/day thereafter. The primary endpoint was G3-4 HG incidence as per NCI-CTCAE v.4.03 at 2 first cycles of treatment. Assessment of glycemia was performed by rigorous self-monitoring blood glucose and local laboratory confirmation in fasting conditions. Secondary endpoints included objective response (ORR), clinical benefit rate (CBR), duration of response (DoR), progression-free survival (PFS), and safety. Sample size was based on a Simon’s two-stage design in cohorts A (H0: G3-4 HG ≥25%; H1: G3-4 HG ≤10%) and B (H0: G3-4 HG ≥40%; H1: G3-4 HG ≤15%). We planned to attain 80% power at the nominal one-sided α level of 0.05 for each cohort. Results: Between Aug 30, 2020, and Mar 10, 2022, 68 pts were enrolled at 18 sites (48 cohort A, 20 cohort B). Median age was 55 (range, 29–79) years and 58.8% pts had visceral disease and an ECOG PS 0. A total of 66 (97.1%) pts had been previously treated with a CDK4/6i and 13 (19.2%) pts had received chemotherapy for advanced disease. Sixty-three (92.6%) pts received fulvestrant as ET (45 cohort A, 18 cohort B). With a median follow-up of 8 (range, 1.6–14.9) months, 28 (41.2%) pts remain on study treatment. Disease progression was the main reason for discontinuation, reported in 32 (47.1%) pts. The primary endpoint of the study was reached, with 1 (2.1%) pts (95%CI, 0.8–9.5; p &amp;lt; 0.001) in cohort A and 3 (15%) pts (95%CI, 4.5–33; p = 0.012) in cohort B experiencing a G3-4 HG episode over the 2 first cycles of treatment. For patients on fulvestrant, G3-4 HG rates were 1 pts (2.2%) and 3 (16.7%) pts for cohorts A and B, respectively. No ALP discontinuation related to HG was reported during the first 2 treatment cycles. Median PFS in all patients was 7.4 months (95%CI, 6–NA). Among pts with measurable disease, ORR was 14 (36.8%) pts (95%CI, 21.8–54). At the time of this analysis, DoR and CBR were still immature. The most common AEs were diarrhea (67.6%; 13.2% G≥3), nausea (67.6%; 0% G≥3), and fatigue (45.6%; 2.9% G≥3). Serious AEs occurred in 15 (22.1%) pts. The main serious AEs were rash (2.9% G≥3) and vomiting (1.5% G≥3). No additional pts reported G≥3 HG after the first 2 cycles. The dose of ALP was reduced according to the protocol in 19 (27.9%) pts. Eight (11.8%) pts permanently discontinued ALP due to AEs, none of whom related to HG. No treatment-related deaths were reported. Conclusions: Prophylactic use of MET substantially reduced the incidence and severity of ALP-related HG with no additional toxicities and could be a new standard for PIK3CA-mutated, HR[+]/HER2[-] ABC pts receiving ALP plus fulvestrant or other ET. Citation Format: Manuel Ruiz Borrego, Pablo Tolosa, Salvador Blanch, Adela Fernández, Ander Urriticoechea, Isabel Blancas, Cristina Saura, Beatriz Rojas, Begoña Bermejo, Jose Ponce, Maria Gión, Elisenda Llabres, Elena Galve, Juan Fernando Cueva, Ana López, José L Alonso-Romero, Santiago González-Santiago, Eduardo Martínez De Dueñas, Fernando Gomez Peralta, Eva Ciruelos, José Manuel Pérez-García, Antonio Llombart-Cussac, Javier Cortés. Metformin (MET) for the prevention of Alpelisib (ALP)-related Hyperglycemia (HG) in PIK3CA-mutated, Hormone Receptor-Positive (HR[+]) HER2-Negative (HER2[-]) Advanced Breast Cancer (ABC): The METALLICA study. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD8-02.

METABOLIC PARAMETERS IN TYPE 2 DIABETIC PATIENTS WITH POSITIVE CANDIDA CULTURES

The gut microbiota plays an important role in host metabolism, immunity, digestibility and even behaviour. Candida spec. is common resident of the gastrointestinal tract and integral part of the microbiota. The aim of the study was to evaluate if positive Candida cultures in the stool influence metabolic parameters in type 2DM patients. 46 patients with type 2 DM and oral antidiabetic treatment, were divided into a study group (S=18 patients with positive Candida sp. cultures in stool) and the control group (C= remaining 28 patients). Besides medical history and clinical examination, all patients were tested for coproculture, fasting glycaemia (FPG), HbA1C, total cholesterol (CL) triglycerides (TG), high- density lipoproteins (HDL) and low- density lipoproteins (LDL). Study group patients had a significantly higher BMI (31.41 ± 5.29 vs. 25.18 ± 3.58; p&lt;0.001); HbA1C (9.8 % ± 1.74 vs 6.9% ± 1.89; p&lt;0.05) as well as FPG (10.87 ± 1.35 vs 7.47 ± 1.03; p&lt;0.01), compared to the control group. Even though the study group patients had higher TG, CL, LDL and HDL, compared to the control group, there was no statistical significance verified. Uncontrolled glucoregulation is one of the host condition which favours candida colonization and subsequent infection. This may be related to the decrease in commensal bacteria, probably as the result of yeast-bacterial competition. On the other hand, we have to keep in mindthat a significantly increased number of Candida colonies can affect the rate of digestion and absorption of carbohydrates and consequently increase the level of glycaemia in patients with diabetes.

HYPOGLYCEMIC EFFECT OF SITAGLIPTIN AND AMINOGUANIDINE COMBINATION IN EXPERIMENTAL DIABETES MELLITUS

The aim of the work was to determine the antidiabetic effect of a sitagliptin and aminoguanidine combination in rats with experimental diabetes mellitus.Materials and methods. The study was carried out on male Wistar rats and C57BL/KsJ-db/db mice. According to the models used, it was divided into 4 series, in which alloxan, steroid-induced (dexamethasone) and streptozotocin-nicotinamide-induced diabetes mellitus (DM) were formed, respectively, in rats, and in the 4 series, obese C57BL/KsJ-db/db mice were used. In the 1 and 2 series, the treatment was started prophylactically – 3 h after the alloxan administration and simultaneously with the dexamethasone administration, in the 3rd and 4th series, the treatment was carried out after the pathology had developed – 7 days after the streptozotocin with nicotinamide administration, and in the obese mice – immediately after their distribution according to the groups. The treatment was carried out with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The treatment was continued till the end of the experiment, which was completed with an oral glucose tolerance test (OGTT) after 4 h of fasting. The obtained data were subjected to statistical processing.Results. In the course of the experiments, it was found out that the prophylactic administration of a sitagliptin and aminoguanidine combination, unlike each of the components, prevented the development of alloxan DM. More effectively than the administration of sitagliptin alone, it reduced the severity of steroid-induced DM, which was expressed in a significantly lower level of fasting glycemia (after 4 h of fasting) and postprandial glycemia (during OGTT). Under the conditions of streptozotocin-nicotinamide-induced DM, the studied combination slowed down the progression of the pathology, and in the obese mice, the course therapeutic administration of sitagliptin and its combination reduced the severity of carbohydrate metabolism disorders (fasting glycemia) and increased the rate of glucose utilization.Conclusion. As an iNOS blocker, aminoguanidine enhances the antidiabetic effect of sitagliptin, preventing the development of alloxan diabetes and reducing the severity of steroid-induced DM when administered prophylactically. When administered therapeutically, it reduces the severity of streptozotocin-nicotinamide-induced DM in rats and type 2 DM in mice with a predisposition to obesity.

Inhibitory Potential of α-Amylase, α-Glucosidase, and Pancreatic Lipase by a Formulation of Five Plant Extracts: TOTUM-63.

Controlling post-prandial hyperglycemia and hyperlipidemia, particularly by regulating the activity of digestive enzymes, allows managing type 2 diabetes and obesity. The aim of this study was to assess the effects of TOTUM-63, a formulation of five plant extracts (Olea europaea L., Cynara scolymus L., Chrysanthellum indicum subsp. afroamericanum B.L.Turner, Vaccinium myrtillus L., and Piper nigrum L.), on enzymes involved in carbohydrate and lipid absorption. First, in vitro inhibition assays were performed by targeting three enzymes: α-glucosidase, α-amylase, and lipase. Then, kinetic studies and binding affinity determinations by fluorescence spectrum changes and microscale thermophoresis were performed. The in vitro assays showed that TOTUM-63 inhibited all three digestive enzymes, particularly α-glucosidase (IC50 of 13.1 µg/mL). Mechanistic studies on α-glucosidase inhibition by TOTUM-63 and molecular interaction experiments indicated a mixed (full) inhibition mechanism, and higher affinity for α-glucosidase than acarbose, the reference α-glucosidase inhibitor. Lastly, in vivo data using leptin receptor-deficient (db/db) mice, a model of obesity and type 2 diabetes, indicated that TOTUM-63 might prevent the increase in fasting glycemia and glycated hemoglobin (HbA1c) levels over time, compared with the untreated group. These results show that TOTUM-63 is a promising new approach for type 2 diabetes management via α-glucosidase inhibition.

Induction of experimental diabetes and diabetic nephropathy using anomer-equilibrated streptozotocin in male C57Bl/6J mice

Streptozotocin (STZ) is widely used to induce experimental diabetes in murine models. However, the ability to induce diabetic nephropathy (DN) is more challenging. It has been recommended to inject STZ at multiple low doses within 15 min after dissolution due to its alleged instability. However, some studies suggest that STZ is stable for days due to equilibration of its two anomers (α and β), 90 min after dissolution, and that this anomer-equilibrated STZ leads to higher survival rates and persistent hyperglycaemia with minimal weight loss. The aim of this study was to determine an optimal dose of anomer-equilibrated STZ to induce kidney tubular damage and compare it with the more commonly used freshly prepared STZ. We hypothesised that anomer-equilibrated STZ provides a better, reproducible experimental model of diabetes-induced kidney damage with improved animal welfare. Body measurements, fasting glycaemia, insulinemia and renal histology were assessed in male C57Bl/6J at two and six months of age treated with fresh (50 mg/kg) or anomer-equilibrated (dose ranging 35–50 mg/kg) STZ or vehicle control. We demonstrated a dose-dependent effect of anomer-equilibrated STZ on the induction of hypo-insulinaemia and hyperglycaemia, as well as body weight in two-month-old mice. Interestingly, in six-month-old mice STZ leads to body weight loss, independently of STZ preparation mode. Anomer-equilibrated STZ provoked moderate to severe kidney tubule structural damage, resulting in significant kidney hypertrophy, whereas freshly prepared STZ only caused mild alterations. In conclusion, our study proposes that anomer-equilibrated STZ provides a robust murine model of diabetes and early-stage diabetic nephropathy, which can be used to test therapeutic approaches to treat and/or prevent renal damage.

Fasting and diurnal blood ketonemia and glycemia responses to a six-week, energy-controlled ketogenic diet, supplemented with racemic R/S-BHB salts

Single doses of exogenous ketone salts (KS) transiently increase circulating beta-hydroxybutyrate (BHB) (∼1mM; 1-2h) regardless of starting levels of ketosis; however, no studies have explored how sustained use of KS influences measures of ketonemia and glycemia. To determine the response to a hypocaloric, well-formulated ketogenic diet (KD), with and without the inclusion of two daily racemic KS doses (6g R-BHB+6g S-BHB per serving) on 1) daily fasting capillary R-BHB and glucose (R-BHB/GLUfast), 2) bi-weekly 13h diurnal BHB and glucose (R-BHB/GLUdiur), 3) three-hours post-KS ingestion kinetics (R-BHBKS), and 4) bi-weekly fasting plasma enantiomer-specific BHB (R/S-BHBplasma). Non-diabetic adults with overweight and obesity were randomized to receive a precisely measured hypocaloric KD (∼75 %en of maintenance) for six weeks, supplemented twice-daily with KS or placebo (PL). A non-randomized comparison group was provided an isonitrogenous/isoenergetic low-fat diet (LFD). All meals were provided to subjects. Capillary blood was collected daily to measure R-BHB/GLUfast and hourly for R-BHB/GLUdiur. Plasma was collected to measure R/S-BHBplasma, insulin, fasting glucose, and insulin resistance (HOMA-IR). Total AUC was calculated using the trapezoidal method. Mean R-BHBfast increased significantly during KD+PL (1.0mM BHB), an effect enhanced 26% during KD+KS. GLUfast AUC was-6% lower during KD+KS versus LFD. Mean R-BHBdiur increased 40% in KD+KS versus KD+PL, whereas GLUdiur decreased 13% during both KDs versus LFD. R-BHBKS peaked (Δ: ∼1mM) 1h after the morning KS dose, but not following the afternoon dose. Both R/S-BHBplasma increased during KD independent of KS inclusion. R-BHBplasma was 50-times greater compared to S-BHBplasma, and the KS augmented S-BHBplasma 50% more than PL. Fasting insulin and HOMA-IR decreased after 14 days independent of diet. A hypocaloric KD was effective at reducing diurnal glucose compared to a LFD independent of weight loss, but twice-daily racemic KS ingestion during KD augmented ketonemia, both as R- and S-BHB, and decreased mean fasting glucose beyond a KD alone. The hypoglycemic effects of KD in combination with exogenous ketones merit further investigation.

Indicators of carbohydrate metabolism in a patient with dyslipidemia and impaired fasting glycemia receiving pitavastatin: a case report

Statins have diabetogenic properties. Pitavastatin is currently considered the only drug in this group that combines high lipid-correcting activity with the absence of a negative effect on carbohydrate metabolism. The article presents a case of correction of carbohydrate metabolism indicators against the background of pitavastatin therapy in a patient with dyslipidemia and impaired fasting glycemia. The optimal algorithms for the examination and treatment of such patients are discussed on the example of this patient.

Influence of Metformin Dose and Treatment Adherence on Glycemic Control, Adiposity, and Cardiovascular Risk Markers in Iraqi Patients with T2DM

Background: Numerous factors, including metformin doses and treatment adherence, may contribute to significant variations in glycemic control and adiposity markers of type 2 diabetes (T2DM) patients. Objectives : This study aims to determine the influence of metformin dose and treatment adherence on glycemic control and adiposity markers in Iraqi patients with T2DM. Methods: Between October 2021 and March 2022, a case-series study at the Diabetes and Endocrinology Center – Baghdad included 153 T2DM patients with a disease duration of more than one year. Clinical and physical examinations were conducted before enrolment. We measured anthropometric variables to calculate the body mass index (BMI), waist-to-hip ratio (WHR), visceral adiposity index (VAI), and other surrogate indicators. We measured glycated hemoglobin (HbA1c), leptin, C-reactive protein (CRP), total cholesterol, HDL-c, and triglycerides in the serum. Results: Increasing metformin doses did not improve the studied parameters. Adherence to treatment significantly influences fasting glycemia, HbA1c level, and the markers of adiposity. Meanwhile, increasing metformin doses is not associated with changes in insulin resistance and cardiovascular disease risk markers. Conclusion: Beyond metformin dose up-titration, treatment adherence affects glycemic control, visceral adiposity, and CVD risk surrogates. Metformin dose up-titration was not linked to insulin resistance and body fat contents.

Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6months of SGLT2i treatment. Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6months, significant reductions were observed in body weight [-2.22kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12months of treatment. SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

Prognostic value of non-alcoholic fatty liver disease fibrosis score in patients undergoing cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an effective option in the treatment of patients with heart failure and wide QRS. Non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been shown to predict cardiac events in several patient populations. However, the relationship between NFS and response to CRT has not been investigated. The aim of the study was to investigate the predictive role of NFS in the assessment of response after CRT. Three hundred thirty-six patients with heart failure undergoing CRT were prospectively studied. Liver fibrosis were assessed according to the non-alcoholic fatty liver disease fibrosis score (NFS), which includes age, body mass index, impaired fasting glycemia or diabetes mellitus, aspartate aminotransferase /alanine aminotransferase ratio, platelets, and albumin. Echocardiographic response to CRT was defined by a ≥15% reduction in left ventricular end-systolic volume at six months at follow-up. Two hundred thirty-eight patients (71%) had CRT response after 6 months of follow-up. Receiver-operator characteristic curve analysis showed NFS cutoff value of<-1.12 for predicting CRT response with a sensitivity of 70.4% and a specificity of 52.9%. The patients were also divided into four groups according to the quartiles of NFS. The proportion of response to CRT was increased with lower level of NFS value. Multivariate logistic regression analysis demonstrated the NFS score<-1.12 and LVIDs were independent predictors of the CRT response. In the second model of analysis which included NFS, quartiles demonstrated that fourth NFS quartile and LVIDs were independent predictors of CRT response. Liver fibrosis assessed by NFS can provide valuable information to predict reverse remodeling in patients undergoing CRT. The present study supports monitoring of NFS to improve preoperative risk stratification of these patients.

The prevalence of diabetes and prediabetes: a population-based study.

Diabetes remains one of the top public health care priorities. Over 6% of the world's population is affected by type 2 diabetes; however, a similar number of individuals may be unaware of this diagnosis. Our population‑basedstudy aimed to investigate the true prevalence of diabetes and prediabetes in the general population of a medium‑sized city in Poland. The analysis included 1051 participants of the Bialystok PLUS population‑based cohort study. In those who did not report a history of diabetes, the oral glucose tolerance test (OGTT) was performed. Medical history data were gathered using standardized questionnaires, and anthropometric as well as body composition measurements were performed. According to the medical history data, a total of 75 participants had diabetes (7.14%). Prediabetes (impaired fasting glycemia [IFG] or impaired glucose tolerance [IGT]) was identified in 410 individuals, including 241 participants with IFG (22.9%) and 169 patients with IGT (16.1%). Moreover, there were 71 individuals (6.75%) who were newly diagnosed with diabetes based on OGTT results. Overall, 146 patients with diabetes (13.8%) were identified. The ratio of lean mass to fat mass differed significantly between the patients with newly diagnosed diabetes and those without impaired glucose metabolism. Our cohort study demonstrated a high prevalence of undiagnosed diabetes in the Białystok population. In addition, we showed that a large group of patients still remains undiagnosed for other hyperglycemic disorders. Abdominal obesity as well as imbalance between the fat and lean mass may predispose to diabetes.

Фенотип формирования метаболического синдрома в перименопаузальной когорте женщин без дисгликемии в зависимости от наличия артериальной гипертензии

Introduction. The high incidence of arterial hypertension (AH) in the population, its close association with menopause and disorders of carbohydrate metabolism with an emphasis on the predictive role of fasting glycemia (FG) for type 2 diabetes mellitus draws attention to the phenotype of the formation of metabolic syndrome (MS) in perimenopause depending on the presence of hypertension without dysglycemia. Aim of the research. To evaluate the associations between blood pressure (BP) levels and FG during the formation of insulin resistant menopausal MS in a cohort of normoglycemic women aged 35–59 years with AH and normotensive. Materials and methods. In the perimenopausal cohort of women aged 35–59 years without dysglycemia (n = 88), 58 women had hypertension, 30 were normotensive. The following were determined: body mass index (BMI), waist circumference (WC), levels of BP, triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), insulin, follicle-stimulating hormone (FSH) and estradiol, FG, TyG and HOMA2 family (HOMA2-IR and HOMA2-%B) indices. Using SPSS (version 17), we estimated the median (25; 75%); intergroup differences according to the Mann-Whitney test; then, the correlation analyses were carried out: according to Spearman (R) and partial (Rpc) to level the influence of age. Results. Significant associations of systolic BP (SBP) and FG levels, direct and mediated through lipid (TG and HDL-C) and anthropometric (WC) parameters of MS, were revealed with most of the correlations being only partially age-dependent. Among these parameters, the mediators of insulin resistance, the associations of SBP and FG with WC are the most pronounced; it is WC that stably correlates with insulin resistance indices, more specifically with TyG. The correlations of TG levels with HDL-C (R = –0.564; p &lt; 0.001) are also relevant when the influence of age is leveled (Rpc = –0.477; p &lt; 0.001); with them, as well as with the levels of insulin and the duration of postmenopause, FG correlates. BP levels, especially systolic, form correlations with insulin resistance indices, more stable with non-insulin TyG index, in contrast to age-dependent relationships with HOMA2-IR. Conclusion. The extensiveness of the revealed correlations between BP and FG levels with markers and factors for the formation of menopausal MS, including the relation of BP with HOMA2-IR indices and especially TyG, reflects its insulin resistant pathogenetic basis. Along with this, significant stable correlations of the duration of postmenopause with FG reflect a high risk of progression to dysglycemia in the analyzed phenotype of metabolic syndrome and allow us to consider menopause as a unique factor contributing to the rapid clustering of MS in women, determining the interest in clarifying its formation trajectories.

Коррекция метаболических нарушений у пациентов с сахарным диабетом 2 типа с помощью ингибитора натрий-глюкозного ко-транспортера 2 типа

Aim: Comprehensive (clinical, laboratory, instrumental) assessment of the clinical efficacy of metabolic disorders correction in patients with type 2 diabetes mellitus using a type 2 sodium-glucose cotransporter inhibitor. Design: Randomized comparative study. Materials and methods. A 26-week study included 130 patients with the presence of visceral obesity (56.3 ± 2.1 years) who did not reach the target parameters of glycated hemoglobin (HbA1c) on metformin monotherapy 2 g/day. The main group (68 people) received canagliflozin 300 mg/day, in combination with metformin 2 g/day; the control group (62 people) continued to receive monotherapy with metformin 2 g/day. At baseline and in 6 months, all patients underwent laboratory and instrumental examination methods, which included an assessment of carbohydrate metabolism (fasting glycemia (FG), postprandial glycemia (PPG), HbA1c); lipid profile (cholesterol levels, high and low density lipoproteins, triglycerides); content of adipocytokines- adiponectin (ADN), leptin (L). Visceral fat area (AVF) was assessed using a bioimpedance analyzer and magnetic resonance imaging (MRI) at the L4 level. Results. In 6 months, both groups showed significant positive dynamics of FG, PPG and HbA1c. In main group, HbA1c decreased by 2.7 ± 0.3% (p &lt; 0.01), in control group by 0.2 ± 0.1% (p &lt; 0.01). The FG and PPG levels in main group decreased by 4.5 ± 0.4 mmol/L (p &lt; 0.01 ) and 5.8 ± 0.5 mmol/L (p &lt; 0.01), respectively, in control group by 1.3 ± 0.2 mmol/L (p &lt; 0.01) and 1.7 ± 0.4 mmol/L (p &lt; 0.01). The level ADN in main group increased by 102.8 ± 4.8 mcg/ml (p &lt; 0.01), in control group by 8.2 ± 2.1 mcg/ml (p &lt; 0.01). L in main group decreased by 10.3 ± 0.9 ng/ml (p &lt; 0.01), in control group by 4.1 ± 0.7 ng/ml (p &lt; 0.01). In main group, there was a decrease in the VFA of by 18.6 ± 2.3 cm2 (p &lt; 0.01) according to MRI, in control group by 4.7 ± 2.4 cm2 (p &lt; 0.01). According to bioimpedance analysis, there was a decrease in the area of AVF by 26.7 ± 3.2 cm2 (p &lt; 0.01) in the main group, and by 4.7 ± 2.5 cm2 (p &lt; 0.01) in the control group. Conclusion. Combination therapy with canagliflozin and metformin makes it possible to achieve high clinical efficacy of carbohydrate metabolism correction in combination with a decrease in visceral fat depot and normalization levels of the main markers of metabolic health. Keywords: type 2 diabetes mellitus, leptin, adiponectin, canagliflozin.

Влияние стажа ожирения на его выраженность и риск развития метаболического синдрома

Objective. To study the structure of exogenous constitutional obesity and metabolic risk in adolescents with different disease duration. Patients and methods. Study design: retrospective, observational, analytical. Adolescents with exogenous constitutional, abdominal type of obesity aged 12 to 17 years (n = 82) who underwent inpatient examination between 2018 and 2023 were included in the study using the continuous sampling method. The structure of obesity and metabolic disorders was assessed, and the association between the degree of obesity, metabolic syndrome, and disease duration was investigated. Results. Class III obesity was diagnosed in 46.3% of adolescents, class II obesity was slightly less common (24.4% of patients), class I obesity and morbid obesity were observed with the same prevalence (14.6%). Metabolic syndrome occurred in 39.0% of cases, with impaired fasting glycemia (52.4%), hyperuricemia (53.7%) and dyslipidemia (34.2%) being frequent pathological conditions. There was a predominance of greater obesity degree in boys and a high prevalence of metabolic syndrome (52.2% of boys and 22.2% of girls (p = 0.007)). It was found that disease duration was positively correlated with the degree of obesity (r = 0.350, p = 0.001), and an increase in metabolic disorders with the progression of obesity was determined (r = 0.299, p = 0.006). At the same time, comparative and correlation analysis, calculation of relative risk and odds ratio did not reveal a statistically significant association between disease duration and risk of metabolic syndrome. Conclusion. The results of this study did not reveal a significant association between metabolically unhealthy obesity and disease duration, but the correlation between disease duration and obesity degree, as well as the increase in metabolic disorders with higher body mass index were established. Key words: metabolic syndrome, obesity duration, exogenous constitutional obesity, adolescents