The Relationship Between Dietary Patterns and Glycemic Variability in People with Impaired Glucose Tolerance.

BACKGROUND: Diurnal glucose fluctuations are increased in prediabetes and might be affected by specific dietary patterns. OBJECTIVES: The present study assessed the relationship between glycemic variability (GV) and dietary regimen in people with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). METHODS: Forty-one NGT (mean age: 45.0 ± 9.0 y, mean BMI: 32.0 ± 7.0 kg/m2) and 53 IGT (mean age: 48.4 ± 11.2 y, mean BMI: 31.3 ± 5.9 kg/m2) subjects were enrolled in this cross-sectional study. The FreeStyleLibre Pro sensor was used for 14 d, and several parameters of GV were calculated. The participants were provided with a diet diary to record all meals. ANOVA analysis, Pearson correlation, and stepwise forward regression were performed. RESULTS: Despite no difference in diet patterns between the 2 groups, GV parameters were higher in IGT than in NGT. GV worsened with an increase in overall daily carbohydrate and refined grain consumption and improved with the increase in whole grain intake in IGT. GV parameters were positively related [r = 0.14-0.53; all P < 0.02 for SD, continuous overall net glycemic action 1 (CONGA1), J-index, lability index (LI), glycemic risk assessment diabetes equation, M-value, and mean absolute glucose (MAG)], and low blood glucose index (LBGI) inversely (r = -0.37, P = 0.006) related to the total percentage of carbohydrate, but not to the distribution of carbohydrate between the main meals in the IGT group. A negative relationship existed between total protein consumption and GV indices (r = -0.27 to -0.52; P < 0.05 for SD, CONGA1, J-index, LI, M-value, and MAG). The total EI was related to GV parameters (r = 0.27-0.32; P < 0.05 for CONGA1, J-index, LI, and M-value; and r = -0.30, P = 0.028 for LBGI). CONCLUSIONS: The primary outcome results showed that insulin sensitivity, calories, and carbohydrate content are predictors of GV in individuals with IGT. Overall, the secondary analyses suggested that carbohydrate and daily consumption of refined grains might be associated with higher GV, whereas whole grains and daily protein intake were related to lower GV in people with IGT.

Insulin secretion and action affect glucose variability in the early stages of glucose intolerance.

AIMS: Since it is unknown whether glucose variability (GV) is increased and whether this is related to worsening of insulin secretion and action in prediabetes, we have assessed insulin secretion and sensitivity, and daily GV in early stages of dysglycemia. MATERIALS AND METHODS: Twenty subjects with normal glucose tolerance (NGT; age 45.0 ± 9.5 years; BMI 31.1 ± 6.4 kg/m2), 25 with NGT and 1hrOGTT>8.6 mmol/L (1hrOGTT; 45.7 ± 8.5 years; 32.4 ± 7.0 kg/m2), and 59 with isolated impaired glucose tolerance (iIGT; 47.7 ± 11.2 years; 31.3 ± 6.1 kg/m2) underwent OGTT and MMTT. CGM was performed with blinded FreeStyle Libre Pro for 24 h under standard conditions. Parameters of beta-cell function, insulin sensitivity and GV were calculated. RESULTS: Overall insulin secretion and action as well as GV progressively worsened across glucose tolerance categories. On a matrix analysis, GV parameters were inversely related to ISSI-2; r = -0.37 to -0.52; p < 0.0001; and IGI; r = -0.28 to -0.48; p < 0.0001 for CV, SD, J-index, LI, HBGI and MAGE. Insulin secretion (IGI) and b-cell function (ISSI-2) emerged as independent contributors to GV in early stage of dysglycemia accounting for about 16%-38% of its variability. CONCLUSIONS: Our results show that daily GV worsens already with mild impairment of glucose tolerance. The increase in GV is inversely related to insulin secretion and action.

Does SGLT2 Inhibition Affect Sympathetic Nerve Activity in Type 2 Diabetes?

SGLT2 inhibitors increase renal glucose excretion and thus decrease both fasting and postprandial plasma glucose levels. The effects of SGLT2 inhibition outweigh those on glycemic control and are also associated with the induction of hemodynamic changes that improve cardiovascular and renal function in people with type 2 diabetes. The exact mechanisms have not yet been completely clarified. This review is focused on the potential relationship between SGLT2 inhibition and sympathetic nerve activity. There is accumulating evidence for a suppressive effect of SGLT2 inhibitors on the sympathetic nerve tone, which might be a putative mechanism for cardiovascular protection in subjects with type 2 diabetes.

The relationship between endogenous secretory RAGE and cardiac autonomic function in prediabetes.

AIMS: The putative protective role of esRAGE for cardiac autonomic function (CAF) remains unclear. To address this question, the present study has assessed the relationship of serum AGEs, sRAGE and esRAGE, and tissue AGEs with CAF in a high-risk population without diabetes. MATERIAL AND METHODS: This study enrolled 48 subjects of mean age 52.7 ± 11.2 years and mean BMI 28.4 ± 6.3 kg/m2 , divided into two groups according to glucose tolerance: 16 with normal glucose tolerance (NGT) and 24 with prediabetes. A standard oral glucose tolerance test (OGTT) was performed. The glucose tolerance was defined according to 2006 WHO criteria. Fasting, 120-minutes glucose, lipids, creatinine, and HbA1c were measured. eGFR was calculated (CKD-EPI). Fasting, 120-minutes insulin (ECLIA method), advanced glycation end products (AGEs), plasma-soluble receptor for AGE (sRAGE), and endogenous secreted isoform of the receptor for AGE (esRAGE), (ELISA method) were assessed. HOMA-IR was calculated. Tissue AGEs were assessed by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAF was evaluated with ANX 3.0 autonomic nervous-monitoring system (ANSAR), applying deep breathing, Valsalva, and standing. RESULTS: There was a significant decline in CAF in prediabetes in comparison with NGT. Serum and tissue AGEs, sRAGE, and esRAGE levels were similar between groups. On the matrix analysis, both sympathetic and parasympathetic activities at baseline and after standing and sympathetic tone during Valsalva were positively related to esRAGE in prediabetes. Multivariate regression analysis showed that esRAGE is an independent contributor to sympathetic, parasympathetic, and total autonomic tone in prediabetes accounting for about 28%, 34%, and 35% of their variances, respectively. CONCLUSION: Our results have demonstrated that CAF is decreased in prediabetes. esRAGE, but not sRAGE, is reciprocally related to CAF, probably opposing the negative effects of glycation.

Endothelial and Autonomic Dysfunction at Early Stages of Glucose Intolerance and in Metabolic Syndrome.

This study evaluated sE-selectin, Endothelin-1, and cardiovascular autonomic neuropathy (CAN) at early stages of glucose intolerance and in metabolic syndrome (MetS). A total of 87 subjects - 39 males, of mean age 45.7±11.6 years and mean BMI 31.4±6.6 kg/m2, divided according to glucose tolerance and the presence of MetS were enrolled. Glucose tolerance was studied during OGTT. Anthropometric indices, blood pressure, HbA1c, lipids, hsCRP, sE-selectin, Endothelin-1, and immunoreactive insulin were measured. Body composition was assessed by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was evaluated by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAN was assessed by ANX-3.0 technology. In the groups, according to glucose tolerance, the prevalence of CAN was 5.7% in normal glucose tolerance (NGT), 8.6% in prediabetes, and 23.5% in newly diagnosed type 2 diabetes (NDD). In the groups, according to the presence of MetS, the prevalence of CAN was 12.3% in those with MetS and 4.8% in those without MetS. Parasympathetic activity was diminished at rest (p=0.048, 0.015, respectively) in NDD as compared to prediabetes and NGT; and there was a numerically elevated heart rate at rest in NDD in comparison to NGT. There was a negative correlation between parasympathetic tone and waist circumference, BMI, and visceral and total fat. There was no difference in the measured endothelial function markers in the groups according to glucose tolerance and MetS. sE-selectin correlated with HOMA-IR (r=0.275, p=0.048). No association between Endothelin-1 levels and assessed metabolic parameters was observed. There is a high prevalence of CAN at early stages of glucose intolerance and in MetS, due to decreased parasympathetic activity. Slight elevation of glycemia and MetS probably do not affect endothelial function, since sE-selectin seems to be related to insulin resistance.

Vitamin D in the Spectrum of Prediabetes and Cardiovascular Autonomic Dysfunction.

Vitamin D is a fat-soluble secosteroid hormone with pleiotropic effects. 1,25-Dihydroxyvitamin D coordinates the biosynthesis of neurotransmitters in the central nervous system, which regulate cardiovascular autonomic function and may explain its putative role in the development of cardiovascular autonomic neuropathy (CAN). CAN is an independent risk factor for mortality in patients with diabetes and prediabetes and is associated with an increased risk of developing type 2 diabetes and cardiovascular disease. Accumulating data indicate the presence of peripheral nerve injury at these early stages of dysglycemia and its multifactorial pathogenesis. Prediabetes is associated with vitamin D insufficiency. Vitamin D is proposed to prevent the progression of glucose intolerance. The putative underlying mechanisms include maintenance of the intracellular calcium concentration, direct stimulation of insulin receptor expression, and enhancement of the insulin response to glucose transporters. Vitamin D exerts a protective effect on peripheral nerve fibers by decreasing the demyelination process and inducing axonal regeneration. The effects of vitamin D supplementation on glucose tolerance and related autonomic nerve dysfunction have been a recent focus of scientific interest. Although well-designed observational studies are available, the causative relation between vitamin D deficiency, glucose intolerance, and CAN is still debatable. One reason might be that interventional studies are unpersuasive with regard to the beneficial clinical effects of vitamin D supplementation. Because of its favorable side effect profile, vitamin D supplementation might represent an attractive therapeutic option for treating the pandemic prevalence of prediabetes and vitamin D deficiency. Vitamin D supplementation can improve glucose tolerance and cardiovascular autonomic function and can thus reduce cardiovascular mortality among subjects with different stages of glucose intolerance and autonomic dysfunction. However, more patient-centered trials on the use of vitamin D supplementation in different conditions are needed.

Comparative Evaluation of the Diagnostic Value of Procalcitonin and hsCRP for the Presence of Mild-to-Moderate Diabetic Foot Infections.

The aim of this study is to compare the efficacy of procalcitonin (PCT) and high-sensitive C-reactive protein (hsCRP) as diagnostic biomarkers in patients with diabetes and mild-to-moderate diabetic foot infections. A total of 119 patients (102 with type 2 diabetes and 17 with type 1 diabetes), of mean age 60.29 ± 10.05 years, divided into 3 groups-diabetic foot ulcer (DFU) with active infection (IDFU group, n = 41), DFU without clinical signs of infection (non-IDFU group, n = 35), and a control group with diabetes without DFU (n = 43). Infection severity was graded according to the International Working Group on the Diabetic Foot guideline-non-IDFU group as Grade 1, IDFU group as Grade 2 (n = 22), and Grade 3 (n = 19). Serum hsCRP was assessed by the immunoturbidimetric method and PCT by the enzyme chemiluminescence immunoassay (ECLIA) method. Levels of white blood cells (WBC) were assessed using the Medonic hematology analyzer and erythrocyte sedimentation rate (ESR) by the Westergren method. Serum hsCRP, WBC count, and ESR were significantly higher in the IDFU group as compared to non-IDFU and control groups, whereas PCT levels did not differ between the groups. hsCRP presented with higher sensitivity (80%), specificity (79%), area under the curve (AUC) 0.856, in comparison to PCT (sensitivity 63%, specificity 62%, AUC 0.617) for the presence of IDFU, as well as in the Grade 3 subgroup (84% sensitivity and specificity, AUC 0.911). The combined model of both markers did not present with better accuracy than using hsCRP alone. In conclusion, hsCRP appears to be a better diagnostic biomarker than PCT in the diagnosis of moderate foot ulcer infection. Both markers fail to distinguish mild infection.

CSII is related to more stable glycemia in adults with type 1 diabetes.

PURPOSE: The purpose of the present study was to compare the basic glycemic control parameters-HbA1c, CV%, and hypoglycemia, as well as quality of life and depression score in patients with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). METHODS: 324 adult patients with type 1 diabetes-146 using CSII and 178 on MDI, were enrolled in this cross-sectional study. HbA1c was assessed in whole blood by immuno-turbidimetric NGSP certified method. CV% was derived from CGM or was calculated from a 9-point capillary blood glucose profile. Hypoglycemia frequency, severity, and awareness were assessed using Clarke's hypoglycemia questionnaire. Quality of life (QOL) was assessed using a questionnaire by the Psychiatric Research Unit and the CES-D scale. RESULTS: CSII group compared to MDI group showed significantly lower HbA1c-7.3% (6.6-8.0%) vs 8.2% (7.2-9.6%) (p < 0.0001), lower CV 27.2% (±9.8) vs 34.7% (±11.3) (p < 0.0001), fewer hypoglycemia episodes (p < 0.0001). There was no significant difference in the frequency of severe hypoglycemia, hypoglycemia awareness, QOL, and depression scores between the two groups. CONCLUSIONS: CSII in type 1 diabetes is related to better and more stable glycemic control compared to MDI.

Vitamin D Status in a Bulgarian Population With Type 2 Diabetes and Diabetic Foot Ulcers.

The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m2, and estimated glomerular filtration rate ≥45 mL/min/1.73m2, were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.

Evaluation of the relationship between cardiac autonomic function and glucose variability and HOMA-IR in prediabetes.

AIMS: The present study aims to investigate the relationship between cardiac autonomic function (CAF) and glucose variability (GV) and HOMA-IR in subjects with prediabetes and normal glucose tolerance (NGT). MATERIAL AND METHODS: Ninety-two subjects (59 with prediabetes and 33 with NGT), of mean age 50.3 ± 11.5 years, mean BMI 30.4 ± 6.0 kg/m2, were included in this cross-sectional study. Glucose tolerance was assessed by OGTT according to WHO 2006 criteria. Glucose, HbA1c, insulin, oxLDL, and 3-Nitrotyrosine were measured. CGM was performed with a blinded sensor (FreeStyle Libre Pro). CAF was assessed by ANX-3.0 technology. RESULTS: GV indices were increased in prediabetes. CAF was suppressed in subjects with any stage of dysglycemia. The prevalence of cardiac autonomic dysfunction was higher in prediabetes -20.3% as compared to NGT -3.0%, p = 0.028. HOMA-IR [OR 1.5 (95% CI: 1.1-2.1), p = 0.010] and time in target range [OR 0.8 (95% CI: 0.67-0.97), p = 0.021] were found to be predictive variables for impaired CAF. Sympathetic and parasympathetic activity negatively correlated with mean glycemia and GV indices and were independently related to JINDEX in prediabetes (F[1, 47] = 5.76, p = 0.021 and F[1, 47] = 5.94, p = 0.019, respectively); and to time above target range in NGT (F[1, 18] = 4.48, p = 0.049 and F[1, 18] = 4.65, p = 0.046, respectively). CONCLUSION: CAF is declined in prediabetes and seems to be related to GV and HOMA-IR at early stages of dysglycemia.

GAD-65 autoantibody associated epilepsy.

Objectives The aim of this report is to describe a case of GAD-65 autoantibody associated epilepcy, diagnosed long before the onset of autoimmune diabetes. Case presentation This report presents a 36-year-old female with type 1 diabetes, diagnosed at the age of 26, and a cryptogenic focal epilepsy with complex partial seizures, with duration of 2-3 min and frequency of 5-6 per month, diagnosed at 16 years of age. Electroencephalography revealed epileptiform abnormalities temporally and centro-parietally on the left and temporally on the right with forward propagation on both sides. Due to the drug refractory seizures, titers of GAD-65 autoantibodies were examined (19 years after the diagnosis of epilepsy and 9 years after the diagnosis of diabetes) and were found to be elevated in serum and cerebrospinal fluid, strongly supporting its autoimmune genesis. Insulin pump therapy was used in this patient with a beneficial effect on glycemia. Conclusions Autoimmune epilepsy is a clinical entity and should be taken into consideration in patients with other autoimmune diseases, especially diabetes, and with drug refractory seizures, even preceding the onset of diabetes. Achieving stable glycemic control, including the usage of the new technologies in type 1 diabetes treatment, is vital in these cases.

Vitamin D binding protein is related to cardiac autonomic function and metabolic status in prediabetes.

A putative causal relationship between vitamin D status and glucose metabolism and a direct effect of vitamin D on cardiac autonomic function (CAF) have been suggested. We hypothesized that vitamin D binding protein (DBP), as a transporter of vitamin D, might also influence CAF and the overall metabolic risk. The present study aims to assess the relationship between DBP and CAF and metabolic status in a high-risk population with prediabetes. A total of 174 subjects (mean age 49.1±12.9 years, mean body mass index 30.2±6.2 kg/m2) were divided into 2 groups according to glucose tolerance: 48 with normal glucose tolerance and 126 with prediabetes. Glucose tolerance was assessed during oral glucose tolerance test, applying 2006 World Health Organization criteria. Fasting and postload glucose and immunoreactive insulin were measured (homeostatic model assessment of insulin resistance and homeostatic model assessment of ß-cell function were calculated). Anthropometric indexes, blood pressure, hemoglobin A1c, creatinine, lipids, high-sensitivity C-reactive protein, total 25-hydroxyvitamin D, DBP (free 25-hydroxyvitamin D was calculated), and intact parathormone were measured. Body composition was estimated by impedance analysis (InBody 720), whereas tissue advanced glycation end products were assessed by skin autofluorescence (AGE Reader, DiagnOptics, the Netherlands). CAF was evaluated by АNX-3.0 system, applying standard autonomic tests. DBP was found to be elevated in women, as well as in the presence of cardiac autonomic dysfunction and metabolic syndrome. DBP was related to parasympathetic activity in both sexes and in prediabetes; to body fat in women and in prediabetes; and to age and high-density lipoprotein cholesterol in men. Vitamin D deficiency was established in 40.8% of the studied cohort. These results support the hypothesis that DBP is associated with CAF and some metabolic parameters in prediabetes.

Islet, thyroid and transglutaminase antibodies in adult Bulgarian patients with type 1 diabetes.

AIM: The aim of the study was to assess the prevalence and relationship of islet antibodies and autoantibodies of the most common associated autoimmune diseases-autoimmune thyroid disease (AITD) and celiac disease, in adult Bulgarian patients with type 1 diabetes of short duration. MATERIAL AND METHODS: 160 type 1 diabetes patients, of mean age 36.3 ± 10.9 years, mean BMI 23.0 ± 4.2 kg/m2 and mean disease duration 1.35 ± 1.69 years were enrolled. Pancreatic islet cell antibodies-glutamic acid decarboxylase antibodies (GAD 65-Ab), tyrosine phosphatase antibodies (IA 2-Ab), and zinc transporter 8 antibodies (ZnT8-Ab), thyroid antibodies-thyroperoxidase and thyroglobulin antibodies, and transglutaminase antibodies (TTG-IgA-Ab) were assessed by ELISA. RESULTS: 87.5% of the patients had one or more of the islet antibodies-78.1% had GAD 65-Ab, 53.1%-ZnT8-Ab, and 34.4%-IA 2-Ab. 5% presented as just ZnT8-Ab positive. GAD 65-Ab identified 90.6% of the antibody positive patients. The addition of IA 2-Ab as a second immunologic marker identified 94.4%, while the use of ZnT8-Ab in second place identified 98.8% of the cases. 24.4% presented with positive thyroid antibodies and 33.8% had AITD. No relation was found between any of the islet antibodies and AITD. None of the patients was TTG-IgA-Ab positive. No significant correlations were established between the antibodies with different organ specificity. CONCLUSIONS: In adult Bulgarian type 1 diabetes patients ZnT8-Ab is an independent diagnostic marker rating second in prevalence and diagnostic significance after GAD 65-Ab. AITD affects about one third of this population and routine screening is required, while screening for celiac disease is not justified.

Development and Validation of Two Self-Reported Tools for Insulin Resistance and Hypertension Risk Assessment in A European Cohort: The Feel4Diabetes-Study.

Early identification of type 2 diabetes mellitus (T2DM) and hypertension (HTN) risk may improve prevention and promote public health. Implementation of self-reported scores for risk assessment provides an alternative cost-effective tool. The study aimed to develop and validate two easy-to-apply screening tools identifying high-risk individuals for insulin resistance (IR) and HTN in a European cohort. Sociodemographic, lifestyle, anthropometric and clinical data obtained from 1581 and 1350 adults (baseline data from the Feel4Diabetes-study) were used for the European IR and the European HTN risk assessment index respectively. Body mass index, waist circumference, sex, age, breakfast consumption, alcohol, legumes and sugary drinks intake, physical activity and sedentary behavior were significantly correlated with Homeostatic Model Assessment of IR (HOMA-IR) and/or HTN and incorporated in the two models. For the IR index, the Area Under the Curve (AUC), sensitivity and specificity for identifying individuals above the 75th and 95th of HOMA-IR percentiles were 0.768 (95%CI: 0.721-0.815), 0.720 and 0.691 and 0.828 (95%CI: 0.766-0.890), 0.696 and 0.778 respectively. For the HTN index, the AUC, sensitivity and specificity were 0.778 (95%CI: 0.680-0.876), 0.667 and 0.797. The developed risk assessment tools are easy-to-apply, valid, and low-cost, identifying European adults at high risk for developing T2DM or having HTN.

The relationship between glucose variability and insulin sensitivity and oxidative stress in subjects with prediabetes.

AIM: The present study assessed the relationship between glucose variability (GV) and insulin levels, insulin resistance and oxidative stress at early stages of glucose intolerance. MATERIAL AND METHODS: A total of 50 subjects - 12 males and 38 females, mean age 55.6 ±â€¯9.7 years, mean BMI 28.4 ±â€¯6.4 kg/m2, divided into 2 groups according to glucose tolerance: 32 with prediabetes and 18 with normal glucose tolerance were included. Glucose tolerance was assessed by OGTT according to WHO 2006 criteria. Plasma glucose and serum insulin were measured at fasting, 120-minute and 180-minute during the test; and oxLDL and 3-Nitrotyrosine - at fasting and 120-minute. HOMA-IR and OGIS indexes were calculated. HbA1c and lipid levels was assessed. Continuous glucose monitoring was performed with a blind sensor (FreeStyle Libre Pro) for a mean period of 13.6 ±â€¯2.3 days. RESULTS: Our results demonstrate significantly increased insulin resistance in subjects with prediabetes, whereas there is no difference in oxidative stress markers between the two groups. OxLDL and 3-NT correlate positively with insulin levels and HOMA-IR and negatively with OGIS in both groups. There is a positive association between oxidative stress markers and 120-minute glucose in the prediabetes group. Insulin levels and HOMA-IR are positively related to plasma glucose and reciprocally to CV and M-Value in prediabetes, since the latter association is with borderline significance after adjustment for hypertension and smoking. CONCLUSIONS: Our results demonstrate a significant correlation between oxidative stress and insulin resistance at early stages of glucose intolerance. Both chronic hyperglycemia and GV seem to be related to insulin levels and insulin resistance, and just postload glycaemia to oxidative stress in prediabetes.

Assessment of glucose variability in subjects with prediabetes.

The aim of the study was to assess glucose variability in subjects with prediabetes by means of CGM. MATERIAL AND METHODS: 32 subjects with prediabetes - mean age 56.6 ±â€¯9.6 years, mean BMI 30.3 ±â€¯5.3 kg/m2 and 18 subjects with normal glucose tolerance (NGT) - mean age 54.4 ±â€¯9.9 years, mean BMI 24.8 ±â€¯6.9 kg/m2, were enrolled. Glucose tolerance was studied during OGTT. HbA1c was measured by NGSP certified method. CGM was performed with FreeStyle Libre Pro sensor. RESULTS: The following indices of glucose variability were significantly higher in the prediabetes group - CV (p < 0.041), J-index (p < 0.014), CONGA (p < 0.047) and GRADE (p < 0.036). A significant increase in HbA1c (p < 0.036), mean interstitial glucose (p < 0.025), time above range (p < 0.018) and a significant decrease in time in range (p < 0.014) was found in prediabetes compared to NGT. Significant correlations between HbA1c and LBGI (r = -0.33, p = 0.02), HBGI (r = 0.31, p = 0.03), CONGA (r = 0.36, p = 0.01), J-index (r = 0.37, p = 0.01) and M-value (r = -0.34, p = 0.02) were established. CONCLUSION: Glucose variability is significantly increased in prediabetes and is an additional parameter in the assessment of glucose homeostasis even at these early stages of glucose dysregulation.

Cardio-metabolic profile of subjects with early stages of glucose intolerance and cardiovascular autonomic dysfunction.

AIMS: The present study evaluates the cardio-metabolic profile of subjects with early stages of glucose intolerance and presence of cardiovascular autonomic dysfunction (CAD). MATERIALS AND METHODS: 478 subjects, of mean age 49.3±13.7years and mean BMI 31.0±6.2kg/m2, divided according to glucose tolerance: 130 with normal glucose tolerance, 227 with prediabetes, and 121 with newly-diagnosed type 2 diabetes, were enrolled. Glucose tolerance was studied during OGTT applying 2006 WHO criteria. Anthropometric indices, blood pressure, HbA1c, serum lipids, hsCRP, and albumin-to-creatinine ratio (ACR) were measured. Body fat distribution was estimated by a bioimpedance method (InBody720, BioSpace). Tissue AGEs accumulation was assessed by skin autofluorescence (AGE-Reader-DiagnOptics™). CAD was assessed by ANX-3.0 method. RESULTS: CAD was found in 24.1% of subjects with any disorder of glucose tolerance in comparison to 12.3% in NGT, OR 2.0 (95% CI: 1.2-3.2), p=0.005. Sympathetic and parasympathetic tone declined with the progression of glucose intolerance. Age, waist circumference, visceral fat area, fasting and 120-min plasma glucose, HbA1c, AGEs, ACR and QTc interval were higher in subjects with CAD, p<0.05. In a logistic regression analysis the panel of age >53years (76% sensitivity, 61% specificity), HbA1c >6.0% (66% sensitivity, 60% specificity), QTc interval >423ms (65% sensitivity, 61% specificity) and presence of arterial hypertension (83% sensitivity, 55% specificity) was related to the presence of CAD - AUC 0.778 (95% CI: 0.73-0.83), p<0.001. CONCLUSION: Our results demonstrate a high prevalence of CAD in early stages of glucose dysmetabolism. Age, HbA1c, QTc interval and presence of arterial hypertension are related to the presence of CAD in this population.

Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance.

AIM: The present study evaluates autonomic and somatic nerve function in different stages of glucose tolerance and its correlation with different cardio-metabolic parameters. MATERIAL AND METHODS: Four hundred seventy-eight subjects, mean age 49.3±13.7years and mean BMI 31.0±6.2kg/m2, divided according to glucose tolerance: 130 with normal glucose tolerance (NGT), 227 with prediabetes (125 with impaired fasting glucose (IFG) and 102 with isolated impaired glucose tolerance (iIGT)), and 121 with newly-diagnosed T2D (NDT2D), were enrolled. Glucose tolerance was studied during OGTT. Antropometric indices, blood pressure, HbA1c, serum lipids, hsCRP and albumin-to-creatinine ratio were assessed. Body composition was estimated by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was assessed by skin autofluorescence (AGE-Reader-DiagnOpticsTM). Electroneurography was performed by electromyograph Dantec Keypoint. Cardiovascular autonomic neuropathy (CAN) was assessed by ANX-3.0 method applying standard clinical tests. RESULTS: CAN was found in 12.3% of NGT, 19.8% of prediabetes (13.2% of IFG and 20.6% of iIGT), and 32.2% of NDT2D. The prevalence of diabetic sensory polyneuropathy (DSPN) was 5.7% in prediabetes and 28.6% in NDT2D. The panel of age, QTc interval, waist circumference, diastolic blood pressure, and 120-min plasma glucose was related to sympathetic activity (F [5451]=78.50, p<0.001). The panel of age, waist circumference, and QTc interval was related to parasympathetic power (F [3453]=132.26, p<0.001). HbA1c and age were related to sural SNAP (F [2454]=15.12, p<0.001). HbA1c and AGEs were related to sural SNCV (F [2454]=12.18, p<0.001). CONCLUSIONS: Our results demonstrate a high prevalence of autonomic and sensory nerve dysfunction in early stages of glucose intolerance. Age, postprandial glycemia, central obesity, diastolic blood pressure and QTc interval outline as predictive markers of CAN; hyperglycemia, glycation and age of DSPN.

Is vaspin related to cardio-metabolic status and autonomic function in early stages of glucose intolerance and in metabolic syndrome?

BACKGROUND: This study aims to assess serum vaspin in early stages of glucose intolerance and in the presence of metabolic syndrome (MetS); and to evaluate vaspin correlation to different cardio-metabolic parameters and autonomic tone in these subjects. METHODS: 185 subjects (80 males and 105 females) of mean age 45.8 ± 11.6 years and mean BMI 31.2 ± 6.3 kg/m(2), divided into groups according to: glucose tolerance, presence of MetS and cardio-vascular autonomic dysfunction (CAD), were enrolled. Glucose tolerance was studied during OGTT. Anthropometric indices, blood pressure, HbA1c, serum lipids, hsCRP, fasting immunoreactive insulin and serum vaspin were measured. Body composition was estimated by impedance analysis. AGEs were assessed by skin fluorescence. CAD was assessed by ANX-3.0. RESULTS: There was no difference in vaspin levels between the groups according to glucose tolerance, presence of MetS, and CAD. Regression analysis revealed independent association between serum vaspin and total body fat in newly diagnosed type 2 diabetes (NDT2D) group, and between serum vaspin and age and total body fat in MetS group. Vaspin negatively correlated with both sympathetic and parasympathetic activity in normal glucose tolerance (NGT) and just with parasympathetic tone in NGT without MetS. CONCLUSION: Our results demonstrate no overt fluctuations in vaspin levels in the early stages of glucose intolerance and in MetS. Total body fat seems to be related to vaspin levels in MetS and NDT2D. Our data show negative correlation between vaspin and autonomic function in NGT, as vaspin is associated with parasympathetic activity even in the absence of MetS.