Anna Stefańska

Low-fructose diet lowers blood pressure and inflammation in patients with chronic kidney disease

BACKGROUND Fructose has been strongly linked with hypertension, hyperuricemia and inflammation in experimental models and humans. However, the effect of low-fructose diet on inflammation, hyperuricemia and the progression of renal disease has not yet been evaluated in patients with chronic kidney disease (CKD). METHODS Twenty-eight patients (age 59 ± 15 years, 17 males/11 females) with Stages 2 and 3 CKD were switched from a regular (basal) (60.0 g/24 h) to a low (12.0 g/24 h) fructose diet for 6 weeks, followed by a resumption of their regular diet for another 6 weeks. Diet was monitored by a dietician. At the baseline, low- and regular-fructose diet ambulatory blood pressure (BP) was measured and blood sampled for renal function (creatinine), inflammatory markers, fasting glucose and insulin and serum uric acid. Twenty-four-hour urine collections were also obtained for creatinine, uric acid, monocyte chemotatic protein-1, transforming growth factor-beta and N-acetyl-beta-D-glucosaminidase. RESULTS The low-fructose diet tended to improve BP for the whole group (n = 28), while significant reduction of BP was only seen in dippers (n = 20) but not in non-dippers (n = 8). No effects on estimated glomerular filtration rate (eGFR) or proteinuria were observed. Serum uric acid was lowered non-significantly with low-fructose diet (7.1 ± 1.3 versus 6.6 ± 1.0 mg/dL, P < 0.1), whereas a significant decrease in fasting serum insulin was observed (11.2 ± 6.1 versus 8.2 ± 2.9 mIU/mL, P < 0.05) and the reduction persisted after return to the regular diet. A slight but not significant reduction in urinary uric acid and fractional uric acid excretion was observed while the patients were on the low fructose diet. The low-fructose diet also decreased high sensitivity C-reactive protein (hsCRP) (4.3 ± 4.9 versus 3.3 ± 4.5 mg/L; P < 0.01) and soluble intercellular adhesion molecule (sICAM) (250.9 ± 59.4 versus 227 ± 50.5 ng/mL; P < 0.05). The hsCRP returned to baseline with resumption of the regular diet, whereas the reduction in sICAM persisted. CONCLUSION Low-fructose diet in subjects with CKD can reduce inflammation with some potential benefits on BP. This pilot study needs to be confirmed by a larger clinical trial to determine the long-term benefit of a low-fructose diet compared to other diets in subjects with CKD.

Metabolic Syndrome and Menopause: Pathophysiology, Clinical and Diagnostic Significance.

Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.

Metabolic Syndrome and Menopause

Menopause is a risk factor for cardiometabolic diseases, including metabolic syndrome (MetS), type 2 diabetes, and cardiovascular diseases. MetS is a constellation of interdependent factors such as insulin resistance, abdominal obesity, dyslipidemia, and hypertension. The prevalence of MetS in postmenopause is due to loss of the protective role of estrogens and increased circulating androgens resulting in changes to body fat distribution and development of abdominal obesity. Excessive visceral adipose tissue plays an important role due to synthesis and secretion of bioactive substances such as adipocytokines, proinflammatory cytokines, reactive oxygen species, prothrombotic, and vasoconstrictor factors. MetS may also impact risk assessment of breast cancer, osteoporosis and chronic kidney disease, and quality of life during the menopausal transition. Increased MetS has stimulated the exploration of new laboratory tests for early detection and therapies.

Association of follicle-stimulating hormone and sex hormone binding globulin with the metabolic syndrome in postmenopausal women

OBJECTIVES We compared the association of follicle-stimulating hormone (FSH) and sex hormone binding globulin (SHBG) with metabolic syndrome (MetS). DESIGN AND METHODS We examined 320 postmenopausal women (148 with MetS and 172 without MetS). RESULTS FSH was more strongly associated with MetS probability in the logistic regression model compared to SHBG. Receiver operating characteristic (ROC) curves comparison showed greater areas under the curve for FSH than SHBG concentrations. CONCLUSIONS FSH exhibited a stronger coherence to MetS than SHBG in postmenopausal women.

Influence of Different Stages of Experimental Chronic Kidney Disease on Rats Locomotor and Postural Skeletal Muscles Microcirculation

Background. Chronic kidney disease (CKD) is associated with muscle excess fatigue and diminished maximal whole body oxygen consumption, which in part could be depended on poor muscle microcirculatory network. The aim of this study was to assume the influence of different stages of CKD on microcirculation vessels in functionally different skeletal muscles—locomotor, the gastrocnemius muscle, and postural, the longissimus thoracis muscle. Methods. Male Wistar rats underwent sham operation (CON), uninephrectomy (CKD 1/2) and subtotal nephrectomy (CKD 5/6). Muscle samples were stained for an alkaline phosphatase to differentiate capillaries. The number of capillaries was estimated by a single observer in 10 μm transverse sections by point counting at a magnification of ×125 using an Image Analysis System Q 500 MC of Leica. Blood pressure and serum creatinine, haptoglobin, MCP-1, VEGF, and PDGF were measured. Results. There were significant differences (p < 0.05) in CD (number of capillaries per 1 mm2 of muscle tissue), C:F (capillary to fiber ratio), and CC/F (capillary contact per fiber). The CKD 1/2 group in gastrocnemius and longissimus muscle had 53% and 33% lower C:F; 56% and 33% lower CD; and 44% and 20% less CC/F than CON, respectively. The CKD 5/6 group in gastrocnemius and longissimus muscle had 46% and 20% lower C:F; 47% and 11% lower CD; and 48% and 25% less CC/F versus control, respectively. Blood pressure was higher in CKD 5/6 vs. CKD 1/2 and CON (145/95 vs. 107/87 and 119/77 mmHg, p < 0.05, respectively). CKD 5/6 had higher creatinine than CKD 1/2 and CON (1.22 vs. 0.83 and 0.74 mg/dL, p < 0.05, respectively). Haptoglobin was higher in CKD 1/2 and CKD 5/6 versus CON (1.68 and 1.63 vs. 0.70 mg/mL, p < 0.05, respectively). MCP-1 was higher in CKD 5/6 and CKD 1/2 versus CON (609 and 489 vs. 292 pg/mL, p < 0.05, respectively). There were no significant differences in serum growth factors concentration between groups. Conclusion. Capillary rarefaction is present in early stages of CKD. These changes are independent of blood pressure and progression of CKD. We suspected that muscle function has a big impact on microvasculature as capillaries rarefaction has been reduced more in locomotor than postural skeletal muscle.

Value of C-reactive protein as a risk factor for acute coronary syndrome: a comparison with apolipoprotein concentrations and lipid profile.

Objective. To investigate whether assessment of C-reactive protein (CRP) and apolipoproteins, besides the traditional lipid profile, enhances the assessment process for the risk of acute coronary syndrome (ACS). Methods. The study group consisted of 220 consecutive patients admitted to hospital within the first 6 hours from the onset of chest pain. Patients were diagnosed with unstable angina (n = 96), non-ST-elevation myocardial infarction (NSTEMI; n = 57), or ST-elevation myocardial infarction (STEMI; n = 67). ACS patients were compared with 116 healthy volunteers in a case-control study. The serum was assayed on admission for CRP, apolipoproteins ApoAI and ApoB100, and lipid parameters. Results. The highest concentrations of CRP were found in NSTEMI and STEMI, with a median value four-fold higher in ACS patients than in controls (P < 0.0001). Only CRP significantly increased the probability of ACS development (adjusted odds ratio for a 1 mg/L increase 1.90; 95% confidence interval [CI] 1.34–2.89) and explained 90% of the variation for ACS development. Similarly, we demonstrated the highest diagnostic accuracy for CRP among all investigated markers (area under the curve 0.80; 95% CI 0.75–0.85). Conclusions. Our study indicates that CRP superiorly to apolipoproteins and lipid profile facilitates the risk stratification for ACS occurrence.

Association of FSH with metabolic syndrome in postmenopausal women: a comparison with CRP, adiponectin and leptin

AIM The aim of this study was to evaluate the usefulness of follicle-stimulating hormone (FSH) determination in the postmenopausal women with metabolic syndrome (MetS) in a comparative analysis with biomarkers such as C-reactive protein (CRP), adiponectin, leptin and leptin-to-adiponectin ratio (L/A). MATERIAL & METHODS 135 postmenopausal women with MetS and 153 without MetS were subjected to examinations. RESULTS The increase in the probability of MetS, when the value of the marker concentration decreased or increased by 1 standard deviation, was two times higher for FSH-based models than for models including CRP and leptin, and was similar to models including adiponectin and L/A. The areas under the ROC curves were 0.78 for FSH, 0.68 for CRP, 0.72 for leptin, 0.76 for adiponectin and 0.80 for L/A. CONCLUSIONS Our results suggest that the FSH concentration assesses the probability of MetS similarly to L/A or adiponectin and better than CRP or leptin in postmenopausal women.

Decreased Hypoxia-Inducible Factor-1α in Gastrocnemius Muscle in Rats with Chronic Kidney Disease

Background/Aims: Hypoxia-inducible factor (HIF)-1α is responsible for increased expression of genes engaged in angiogenesis. Our previous study indicated capillary rarefaction and atrophy of glycolytic fibers, mainly in locomotor muscles of uremic animals. Perhaps these changes are secondary to disturbances of HIF-1α in skeletal muscles. Methods: Expression of HIF-1α at mRNA and protein levels, as well as mRNA of vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS), in gastrocnemius muscle (MG) and longissimus thoracic muscle (ML) were measured by RT-PCR and Western blot. Rats were randomized to subtotal nephrectomy (CKD5/6), uninephrectomy (CKD1/2) or sham operation (controls). Results: For CKD5/6 versus controls, mRNA levels for HIF-1α, VEGF-A, VEGFR-1 and VEGFR-2 were significantly reduced only in MG, while eNOS was significantly decreased and iNOS was significantly increased only in ML. Western blot analysis indicated significantly increased HIF-1α protein levels in MG and ML from CKD1/2 animals versus controls, whereas in the CKD5/6 group, the level of HIF-1α protein decreased significantly in MG and increased significantly in ML versus controls and CKD1/2. Conclusion: The reduced expression of HIF-1α mRNA and protein in locomotor muscle from CKD5/6 animals may be involved in the pathogenesis of uremic myopathy. Increased expression of iNOS in the postural muscles may act as a protective factor through HIF-1α stabilization.

Impact of fructose diet and renal failure on the function of pancreatic islets.

Objectives This study was designed to evaluate the impact of fructose-rich diet and chronic kidney disease (CKD) on the in vitro function of pancreatic islets. Methods Fifty-four rats were divided into 3 equal groups as follows: control, rats with CKD 1/2 that underwent surgical uninephrectomy, and rats with CKD 5/6 that underwent uninephrectomy and kidney cortex mass resection. Each group was further assigned to 3 diet protocols—regular diet, regular diet with 10% fructose (F10), and 60% fructose-rich diet (F60). After 8 weeks of insulin administration, C-peptide, glycated hemoglobin level, serum urea nitrogen, creatinine clearance, and homeostasis model assessment of insulin resistance were evaluated. Static glucose insulin stimulation test of isolated pancreatic islets and histologic analysis of pancreatic tissue were performed. Results The F10 diet increased the levels of insulin and C-peptide in all groups. Homeostasis model assessment of insulin resistance was increased in all animals fed with fructose. The elevated levels of creatinine and diminished creatinine clearance were detected in CKD 5/6 rats fed with 60% fructose-rich diet. The F10 diet resulted in high levels of serum insulin and C-peptide and glucose-stimulated insulin secretion. Fructose-rich diet increased the islet size and number, with irregular morphology and exocrine tissue fibrosis. Conclusions The fructose-rich diet accelerates the progression of CKD and affects the pancreatic islet function.

Comparison between C-reactive protein and adipocyte fatty acid-binding protein as a component of metabolic syndrome in middle-aged women

OBJECTIVES We compared the diagnostic accuracy of CRP and adipocyte fatty acid-binding protein (A-FABP) for the metabolic syndrome (MS). DESIGN AND METHODS We examined 310 middle-aged Caucasian women. RESULTS CRP and AFABP values were significantly associated with the MS probability in the logistic regression model. Operating characteristic curves comparison showed similar areas under the curve. CONCLUSIONS Measurement of A-FABP is equivalent to CRP in the diagnostic utility of the MS.