Metabolic parameters in diabetic neuropathic patients after treatment with pregabalin.

OBJECTIVE: To assess metabolic parameters in patients with diabetic peripheral neuropathy (DPN) before and after 3 months treatment with a flexible dose pregabalin. METHODS: This is a prospective clinical trial. The metabolic parameters observed and recorded after 3 months treatment with a flexible dose pregabalin (n=331). RESULTS: The lipid profile parameters were significantly improved after treatment, total cholesterol, TC (P<0.01, 95% CI, 25.91-41.98), low-density lipoprotein, LDL (P<0.01, 95% CI, 21.11-34.80), triglycerides, TG (P<0.001, 95% CI, 56.43-79.26), all the three parameters significantly decreased while high-density lipoprotein, HDL, significantly increased (P<0.05, 95% CI, -8.61 to -5.51). Microalbumin mean was 16±1.39 before treatment versus 6.5±0.59 after treatment. Glycolated hemoglobin, HbA1c mean was 9.6±0.099 before pregabalin therapy and 7.6 ±0.06 after. BMI mean was 33.5±0.45 before versus 31.1±0.33 after (P<0.001). HbA1C was positively correlated with DPN severity before treatment (r=0.18, P<0.01). Same results were observed with weight and waist circumference (r=0.17, P<0.01, r=0.14, P<0.05 respectively). Oral anti diabetic medications (OAD) were also positively correlated to DPN severity before treatment (r=0.115, P<0.05). CONCLUSIONS: Prompt treatment of DPN has a significant effect on the metabolic parameters.

alpha2a adrenoceptors regulate phosphorylation of microtubule-associated protein-2 in cultured cortical neurons.

Adrenoceptors have been suggested to mediate neuronal development. This study revealed the expression of alpha2A adrenoceptors in the cortical plate of fetal mouse cerebral wall. The effects of alpha2A adrenoceptor on dendrite growth were investigated in primary neuronal cultures. Application of alpha2 adrenoceptor agonists, BHT 933 or UK 14304 for 24 or 72 h resulted in a 1.5-2-fold increase in dendrite lengths. This effect was blocked by alpha2 adrenergic antagonists, RX 821002 or yohimbine, as well as a alpha2A selective antagonist, BRL 44408, but not by alpha2B/alpha2C selective antagonists ARC 239, imiloxan and rauwolscine. Guanfacine, a alpha2A selective agonists, also significantly increased the dendrite lengths in culture. These results suggest that the morphological effect is wholly attributable to alpha2A adrenoceptor activation. We further tested the hypothesis that alpha2A adrenoceptors act through altering the phosphorylation state of microtubule-associated protein 2. The results showed that the phosphorylation of microtubule-associated protein 2 was significantly reduced on both serine and threonine residues by over 40% after 2 h of application of guanfacine and was maintained at this low level for a prolonged time up to 96 h. These findings suggest that alpha2A adrenoceptors regulate the phosphorylation of microtubule-associated protein 2, which in turn mediates dendrite growth of cortical neurons.