Visceral Obesity and Hemostatic Profile in Patients with Type 2 Diabetes: The Effect of Gender and Metabolic Compensation

BACKGROUND: Type 2 diabetes (T2DM) patients are characterized by a very high risk of cardiovascular diseases. Among the factors that are responsible for this phenomenon are abdominal obesity and hemostatic abnormalities. AIM OF THE STUDY: To examine the association of the markers of coagulation and fibrinolysis with the parameters of abdominal obesity and metabolic compensation in T2DM patients. METHODS: 46 T2DM patients participated in the study: 24 men (mean age 61.1 ± 7.9 years) and 22 postmenopausal women (mean age 62.6 ± 8.7 years). In each patient the content and distribution of fatty tissue was measured by a dual energy X-ray absorptiometry method (DEXA). The central abdominal fat/gynoid hip fat (CAF/GF) ratio was calculated. The following hemostatic parameters were measured: fibrinogen (Fb), factor VII (fVII), antithrombin III (ATIII), C protein (pC), tissue plasminogen activator inhibitor (PAI-1) and alpha 2 antiplasmin (alpha2 AP). In addition, the biochemical indices of metabolic compensation were measured: HbA1c, glucose levels and lipids. RESULTS: Patients of both genders were divided according to median CAF/GF ratio. The activity of PAI-1 was significantly higher in women with CAF/GF ratio ≥ 0.88 as compared to those with CAF/GF < 0.88 (2.64 ± 1.28 vs. 1.61 ± 0.27 U/ml, p < 0.05). The activity of ATIII was significantly lower in men with CAF/GF ratio ≥ 1.17, as compared to those with CAF/GF < 1.17 (105.10 ± 10.02 vs. 113.42 ± 10.72 %, p < 0.05). There was a significant correlation between the CAF/GF ratio and the activity of PAI-1 in women (r = 0.30, p < 0.05). In addition, in men the CAF/GF ratio was negatively correlated with ATIII activity (r = -0.44, p < 0.05). Multiple stepwise regression analysis demonstrated independent association between the CAF/ GF ratio and the activity of PAI-1 (p < 0.001), and between the CAF/GF ratio and the activity of alpha2 AP (p < 0.01). There was an independent association between the concentration of HbA1c and the concentration of Fb (p < 0.001) and between triglycerides and the activity of fVII (p < 0.01). CONCLUSIONS: The results of our study show that the patients with T2DM and with higher markers of abdominal obesity measured by DEXA show fibrinolysis impairment and thrombinogenesis elevation compared to those with lower abdominal obesity markers. Independent factors determining hypercoagulation also include metabolic control and lipids. Hemostatic disorders place subjects with diabetes and abdominal obesity at risk of developing vascular complications

Cystatin C is not a good candidate biomarker for HNF1A-MODY.

Cystatin C is a marker of glomerular filtration rate (GFR). Its level is influenced, among the others, by CRP whose concentration is decreased in HNF1A-MODY. We hypothesized that cystatin C level might be altered in HNF1A-MODY. We aimed to evaluate cystatin C in HNF1A-MODY both as a diagnostic marker and as a method of assessing GFR. We initially examined 51 HNF1A-MODY patients, 56 subjects with type 1 diabetes (T1DM), 39 with type 2 diabetes (T2DM) and 43 non-diabetic individuals (ND) from Poland. Subjects from two UK centres were used as replication panels: including 215 HNF1A-MODY, 203 T2DM, 39 HNF4A-MODY, 170 GCK-MODY, 17 HNF1B-MODY and 58 T1DM patients. The data were analysed with additive models, adjusting for gender, age, BMI and estimated GFR (creatinine). In the Polish subjects, adjusted cystatin C level in HNF1A-MODY was lower compared with T1DM, T2DM and ND (p < 0.05). Additionally, cystatin C-based GFR was higher than that calculated from creatinine level (p < 0.0001) in HNF1A-MODY, while the two GFR estimates were similar or cystatin C-based lower in the other groups. In the UK subjects, there were no differences in cystatin C between HNF1A-MODY and the other diabetic subgroups, except HNF1B-MODY. In UK HNF1A-MODY, cystatin C-based GFR estimate was higher than the creatinine-based one (p < 0.0001). Concluding, we could not confirm our hypothesis (supported by the Polish results) that cystatin C level is altered by HNF1A mutations; thus, it cannot be used as a biomarker for HNF1A-MODY. In HNF1A-MODY, the cystatin C-based GFR estimate is higher than the creatinine-based one.This article is freely available via Open Access. Click on the ‘Additional Link’ above to access the full-text from the publisher’s site.DHCS/07/07/008/Department of Health/United Kingdo