Background: In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. Methods: Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. Results: Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05). Conclusions: Establishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([^99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = −0.27 and −0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Carotid artery intima–media thickness (cIMT), a pre-clinical vascular change that accompanies atherosclerosis is considered as a cardiovascular risk factor. Coagulation factor XIII (FXIII) stabilizes the fibrin clot and increases its resistance to fibrinolysis. Regarding FXIII Val34Leu polymorphism, the protective effect of the Leu34 allele in the presence of elevated fibrinogen levels against myocardial infarction was demonstrated. Our aim was to investigate the effect of FXIII polymorphisms on cIMT. Patients with obesity (n = 69), type 2 diabetes mellitus (T2DM) (n = 104), and age- and sex-matched healthy controls (n = 82) were enrolled. FXIII polymorphisms (Val34Leu, His95Arg, Intron-K C>G) were determined by RT-PCR with FRET detection and melting curve analysis. cIMT was determined by B-mode ultrasound. Differences in cIMT between control (median: 0.5965, IQR: 0.5115–0.6580 mm) and T2DM (median: 0.7105, IQR: 0.5948–0.7568 mm), as well as between obese (median: 0.6105, IQR: 0.5455–0.6780 mm) and diabetic groups, were found (p < 0.0001 and p = 0.003, respectively). Genotype and allele frequencies of the studied polymorphisms did not differ between subgroups. In the study group (n = 255) after adjustment for age and sex, the presence of Intron-K G allele showed a significant and independent protective effect against cIMT progression in a separate model (p = 0.005) and after adjusting for other parameters associated with cIMT (p = 0.015). FXIII Intron-K G allele provides a protective effect against subclinical vascular disease in the studied population, and this effect is independent of the presence of obesity, as well as T2DM, Leu34 allele, and fibrinogen levels.