Vascular Damage and Glycometabolic Control in Older Patients with Type 2 Diabetes.

Diabetes is one of the main risk factors for vascular damage, including endothelial dysfunction and arterial stiffness. The aim of this study was to compare selected parameters of vascular damage in patients with type 2 diabetes (T2D) in different age categories and to determine their relationship to indicators of glycometabolic control. A total of 160 patients with T2D were included in this cross-sectional study. They were divided into four age quartiles (with mean ages of 42.1 ± 4.5, 51.6 ± 1.4, 59.2 ± 3.0, and 69.8 ± 3.8, respectively). All subjects were evaluated for indicators of glycometabolic control and for arterial stiffness parameters along with markers of endothelial damage-tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF). The oldest compared to the youngest participants showed significantly increased parameters of arterial stiffness (augmentation pressure 13.4 ± 8.6 vs. 6.7 ± 4.4 mm Hg, augmentation index 26.2 ± 11.3 vs. 19.6 ± 9.2 mm Hg, aortic pulse pressure 47.7 ± 17.1 vs. 33.7 ± 10.4 mm Hg, and pulse wave velocity 11.9 (10.1-14.3) vs. 8.2 (7.7-9.8) m/s) despite having similar glycometabolic control. Arterial stiffness parameters were mainly associated with age and blood pressure. Age and systolic blood pressure were major determinants of arterial stiffness regardless of glycometabolic control. The oldest patients also had the highest levels of vWF (153.7 ± 51.9 vs. 121.7 ± 42.5 %) but the lowest levels of PAI-1 (81.8 ± 47.5 vs. 90.0 ± 44.9 ng/mL). Markers of endothelial dysfunction correlated with metabolic parameters, but did not correlate with arterial stiffness. Age and systolic blood pressure are major determinants of arterial stiffness in patients with T2D regardless of glycometabolic control, whereas an unfavorable metabolic profile is mainly related to endothelial dysfunction. These results suggest a differential contribution of cardiometabolic risk factors to vascular damage in T2D patients over their lifetime.

Fasting Plasma Glucose and Its Relationship to Anthropometric Phenotype in Women Diagnosed with Gestational Diabetes According to IADPSG Criteria.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by new-onset hyperglycemia in pregnancy. According to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations, GDM may be diagnosed based on repeatedly increased fasting glucose levels in the first trimester, or later, the detection of increased fasting glucose and/or increased glucose levels during a 75 g oral glucose tolerance test (OGTT). The study aimed to assess whether differences may be found between women diagnosed with GDM by fasting glucose or glucose challenge tests in early or late pregnancy. METHODS: The retrospective observational study enrolled 418 women diagnosed with GDM in accordance with the IADPSG criteria: early pregnancy fasting plasma glucose (FPG) ≥ 5.1 mmol/L; late pregnancy FPG ≥ 5.1 mmol/L (0 min) and/or postprandial plasma glucose (PPG) ≥ 10.0 mmol/L (60 min), PPG ≥ 8.5 mmol/L (120 min) 75 g OGTT. The analyses included anthropometric parameters at the beginning and during pregnancy, laboratory values of glycated hemoglobin, fructosamine, birth weight measures and the presence of neonatal complications. RESULTS: There were significant differences in body weight (78.3 ± 19.1; 74.0 ± 16.7; 67.2 ± 15.7 kg) and body mass index (BMI) (27.9 ± 6.6; 26.4 ± 5.8; 24.4 ± 5.2 kg/m2) in early pregnancy. Differences were also found in gestational weight gain (9.3 ± 6.8 vs. 12.4 ± 6.9 vs. 11.1 ± 4.7 kg) and the need for insulin therapy (14.7%; 7.1%; 4.0%). The study revealed no difference in the presence of neonatal complications but differences in birth weight (3372.2 ± 552.2 vs. 3415.6 ± 529.0 vs. 3199.0 ± 560.5 g). CONCLUSIONS: Gestational diabetes, characterized by FPG ≥ 5.1 mmol/L in early pregnancy, is associated with higher body weight and BMI at the beginning of pregnancy as well as with a higher risk for insulin therapy and increased birth weight.

Non-altered incretin secretion in women with impaired fasting plasma glucose in the early stage of pregnancy: a case control study.

BACKGROUNDS: Glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) may be involved in pathogenesis of gestational diabetes mellitus (GDM). The aim was to compare GLP-1 and GIP production in fasting state and during 3 h mixed meal tolerance test (MMTT) measured by mean area under the curve (AUC) between pregnant women with normal and impaired fasting glucose in an early phase of pregnancy, and healthy non-pregnant controls. METHODS: This study was undertaken as a case-control study. Repeated measurement of fasting plasma glucose ≥ 5.1 mmol/L and < 7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes according to IADSPG criteria was used to find women with impaired fasting glucose (n = 22). Age-matched controls consisted of healthy pregnant (n = 25) and non-pregnant (n = 24) women. In addition to incretins, anthropometric parameters and markers of insulin resistance and beta-cell function were assessed. Variables were summarized as median (interquartile range). RESULTS: Fasting GLP-1 and GIP concentration or their AUC during MMTT did not significantly differ between pregnant women with impaired fasting plasma glucose [GLP-1AUC 19.0 (53.1) and GIPAUC 302 (100) pg/mL/min] and healthy pregnant women [GLP-1AUC 16.7 (22.3) and GIPAUC 297 (142) pg/mL/min] or non-pregnant controls [GLP-1AUC 16.8 (9.8) and for GIPAUC 313 (98) pg/mL/min]. Although women with impaired fasting glucose were more obese and showed decreased beta-cell function, there were not significant correlations between incretin production and parameters of insulin secretion, insulin resistance, or obesity. CONCLUSIONS: Women with impaired fasting plasma glucose did not show altered incretin production in the first trimester of pregnancy. In contrast to type 2 diabetes, impaired incretin secretion does not seem to play a major role in the early development of GDM.

Specific gut bacterial and fungal microbiota pattern in the first half of pregnancy is linked to the development of gestational diabetes mellitus in the cohort including obese women.

Aims: Gestation is linked to changes in gut microbiota composition and function. Since gestational diabetes mellitus (GDM) can develop at any time of the pregnancy, we stratified the women into four groups according to the time and test used for the diagnosis. We focused on the gut microbiota pattern in early pregnancy to detect changes which could be linked to later GDM development. Methods: We collected stool samples from 104 pregnant women including obese individuals (first trimester body mass index median was 26.73). We divided the women into four groups according to routine screening of fasting plasma glucose (FPG) levels and oral glucose tolerance test (oGTT) in the first and third trimesters, respectively. We processed the stool samples for bacterial 16S rRNA and fungal ITS1 genes sequencing by Illumina MiSeq approach and correlated the gut microbiota composition with plasma short-chain fatty acid levels (SCFA). Results: We found that gut bacterial microbiota in the first trimester significantly differs among groups with different GDM onset based on unweighted UniFrac distances (p=0.003). Normoglycemic women had gut microbiota associated with higher abundance of family Prevotellaceae, and order Fusobacteriales, and genus Sutterella. Women diagnosed later during pregnancy either by FGP levels or by oGTT had higher abundances of genera Enterococcus, or Erysipelotrichaceae UCG-003, respectively. We observed significant enrichment of fungal genus Mucor in healthy pregnant women whereas Candida was more abundant in the group of pregnant women with impaired oGTT. Using correlation analysis, we found that Holdemanella negatively correlated with Blautia and Candida abundances and that Escherichia/Shigella abundance positively correlated and Subdoligranulum negatively correlated with plasma lipid levels. Coprococcus, Akkermansia, Methanobrevibacter, Phascolarctobacterium and Alistipes positively correlated with acetate, valerate, 2-hydroxybutyrate and 2-methylbutyrate levels, respectively, in women with GDM. Conclusions: We conclude that there are significant differences in the gut microbiota composition between pregnant women with and without GDM already at the early stage of pregnancy in our cohort that included also overweight and obese individuals. Specific microbial pattern associated with GDM development during early pregnancy and its correlation to plasma lipid or SCFA levels could help to identify women in higher risk of GDM development.

Adiponectin, A-FABP and FGF-19 Levels in Women with Early Diagnosed Gestational Diabetes.

Background: Adiponectin, adipocyte fatty acid-binding protein (A-FABP), and fibroblast growth factor-19 (FGF-19) belong to proteins involved in glucose metabolism regulation. The aims of the study were to compare the plasma levels of these proteins in women with early diagnosed gestational diabetes mellitus (GDM) to those in healthy controls and to investigate their changes during pregnancy after early intervention. Methods: The study was undertaken as a case-control study. Early GDM diagnosis was based on repeated fasting plasma glucose ≥5.1 and <7.0 mmol/L during the first trimester of pregnancy and exclusion of overt diabetes. Age-matched controls comprised healthy pregnant and non-pregnant women. In addition to adipokines, clinical parameters and measures of glucose control were assessed. Results: Women with GDM (n = 23) had significantly lower adiponectin and higher A-FABP levels compared to healthy pregnant (n = 29) or non-pregnant (n = 25) controls, while no significant differences in FGF-19 between the groups were found. The therapeutic intervention shifted adiponectin and A-FABP levels in GDM women towards concentrations of healthy pregnant controls. Adipokines were associated with visceral adiposity and glucose control. Conclusion: Women with GDM showed altered adipokine production even in the first trimester of pregnancy. Early therapeutic intervention not only improved glucose control but also normalized impaired adipokine production.

Retinal oxygen saturation is associated with HbA1c but not with short-term diabetes control, internal environment, smoking and mild retinopathy - ROXINEGLYD study.

PURPOSE: Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions. METHODS: Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2 . RESULTS: Wilcoxon signed-rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found. CONCLUSION: This study confirmed the association of venous SatO2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.

Hypertriglyceridemic Waist in Patients with Type 2 Diabetes: Its Relationship to Selected Markers of Vascular Damage.

Background: To evaluate the association between hypertriglyceridemic waist (HTGW), a promising marker of visceral adiposity and cardiovascular (CV) risk, and different indicators of vascular damage in type 2 diabetes (T2D) patients. Methods: This case-control study included 161 patients with T2D (91 males, 70 females) and 40 healthy controls (24 males, 16 females). HTWG was defined as waist circumference >90 cm in men or >85 cm in women and triglyceride concentrations >2 mmol/L. In addition to anthropometric and metabolic parameters, markers of endothelial dysfunction, namely von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1), were assessed. Arterial stiffness parameters were examined using the SphygmoCor system. Results: Individuals with T2D and HTGW showed the highest elevation of PAI-1 levels and significantly increased vWF levels compared with healthy controls. No significant differences in arterial stiffness markers were observed between T2D individuals. Age and, for several markers, systolic and/or diastolic blood pressure were identified as the main predictors for arterial stiffness, whereas PAI-1 and vWF levels were predicted by metabolic parameters. Conclusions: HTGW represents increased CV risk in T2D patients, mainly due to endothelial damage. The presence of HTGW had no significant effect on arterial stiffness compared with other T2D individuals.

Circulating levels of selected adipokines in women with gestational diabetes and type 2 diabetes.

BACKGROUNDS: Adiponectin, adipocyte-fatty acid binding protein (A-FABP), and Wnt1 inducible signaling pathway protein-1 (WISP-1) are adipokines closely associated with insulin resistance. The aim of the study was to compare their levels in women with gestational diabetes (GDM), type 2 diabetes mellitus (T2DM) and healthy controls and determine their relation to metabolic parameters. METHODS: Women with GDM, T2DM and healthy women were included in this cross-sectional study. In addition to adipokines, anthropometric, lipid parameters, markers of insulin resistance and glucose control were assessed in all participants. RESULTS: Compared to healthy controls (n = 35) significantly lower levels of adiponectin were detected in women with GDM (n = 50), whereas in women with T2DM (n = 50) higher levels of A-FABP and WISP-1 and lower levels of adiponectin were found. Women with T2DM had also lower levels of adiponectin and higher levels of A-FABP compared to women with GDM. A-FABP and adiponectin were independently associated with levels of triglycerides, HDL-cholesterol and C-peptide insulin resistance index. WISP-1 correlated only with waist circumference. CONCLUSIONS: Adverse adipokines production reflecting dysfunctional fat tissue is less presented in women with GDM than in women with T2DM, but more expressed compared to healthy women.

Relationship of Selected Adipokines with Markers of Vascular Damage in Patients with Type 2 Diabetes.

BACKGROUND: In this study we compared levels of selected adipokines between patients with type 2 diabetes (T2D) and healthy individuals and we determined their relationship with early vascular damage markers. METHODS: Seventy-seven subjects: 56 patients with T2D (34 men and 22 women) and 21 healthy controls (8 men and 13 women) were examined in this cross-sectional study. Selected adipokines [adiponectin, adipocyte fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF-21), C1q/TNF-related protein 9 (CTRP-9), and allograft inflammatory factor-1 (AIF-1)] with possible cardiovascular impact were measured in all participants. To identify markers of vascular damage von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and arterial stiffness parameters were examined in all the subjects. RESULTS: When compared with healthy controls, T2D had significantly higher levels of A-FABP [50.0 (38.1-68.6) vs. 28.6 (23.6-32.9) ng/mL, P < 0.0001] and lower levels of adiponectin [5.9 (4.3-9.0) vs. 11.3 (8.7-14.8) µg/mL, P < 0.0001]. Differences in other adipokines were not statistically significant. Adiponectin level correlated negatively with vWF levels (ρ = -0.29, P < 0.05) and PAI-1 (ρ = -0.36, P < 0.05) and A-FABP positively with vWF (ρ = 0.61, P < 0.05) and PAI-1 (ρ = 0.47, P < 0.05) and augmentation index (ρ = 0.26, P < 0.05). Multivariate regression analysis showed independent association between A-FABP and vWF (b = 0.24, P < 0.05). CONCLUSIONS: Patients with T2D have significantly higher levels of A-FABP and lower levels of adiponectin. These adipokines correlate with indicators of vascular damage and could contribute to cardiovascular risk in patients with T2D. A-FABP may participate in direct endothelium damage.

Pulse wave analysis and diabetes mellitus. A systematic review.

Cardiovascular (CV) disease is the primary cause of death in diabetic patients and one of the explanations may be increased arterial stiffness. Arterial stiffness assessment using pulse wave analysis, is a predictive factor of CV events. The aim of this paper is to review the current knowledge of relations between diabetes mellitus and pulse wave analysis. A MEDLINE search was performed to retrieve both original and review articles addressing the relations and influences on arterial stiffness in diabetics. Pulse wave analysis is considered as a gold standard in CV risk evaluation for patients at risk, especially diabetics. Arterial stiffness assessment may be helpful for choosing more aggressive diagnostic and therapeutic strategies, particularly in younger patients to reduce the incidence of CV disease in these patients.

New-onset diabetes mellitus after renal transplantation.

BACKGROUND AND AIM: Diabetes mellitus is a very common metabolic disease with a rising incidence. It is both a leading cause of chronic renal disease and one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. The aim of this paper is to review current knowledge of NODAT including risk factors, diagnosis and management. METHODS: A MEDLINE search was performed to retrieve both original and review articles addressing the epidemiology, risk factors, screening and management of NODAT. We also focused on microRNAs as potential biomarkers of NODAT. RESULTS AND CONCLUSION: Understanding the risk factors (both modifiable-e.g. obesity, viruses, and unmodifiable-e.g. age, genetics) may help reduce the incidence and impact of NODAT using pre- and post-transplant management. This can lead to better long-term graft function and general transplant success.