Factors associated with improvement in waist-to-height ratio among newly diagnosed type 2 diabetes patients treated with acarbose or metformin: A randomized clinical trial study.

BACKGROUND: The waist-to-height ratio (WHtR) is a promising anthropometric measure used to evaluate cardiovascular risk in diabetes and metabolic syndrome patients. The metformin and acarbose in Chinese as the initial hypoglycaemic treatment trial demonstrated that acarbose and metformin reduced the WHtR after 24 wk of treatment. AIM: To investigate the factors associated with a decrease in the WHtR in newly diagnosed Chinese type 2 diabetes patients receiving acarbose or metformin monotherapy. METHODS: At 24 wk, 343 patients in the acarbose treatment and 333 patients in the metformin treatment were included in this analysis. On the basis of the reduction in the WHtR, these participants were divided into the following two groups: Low ΔWHtR group and high ΔWHtR group. Metabolic and related parameters associated with a high ΔWHtR were investigated using univariate and multivariate logistic regression analyses. RESULTS: A significant decrease in the WHtR was observed in both treatment groups (acarbose: -0.015, 95% confidence interval [CI]: -0.018 to -0.012, P < 0.001; metformin: -0.013, 95%CI: -0.016 to -0.010, P < 0.001). In both the acarbose and metformin groups, the WHtR of the women was more likely to be reduced than that of the men. In the acarbose group, a lower baseline area under the curve of glucagon-like peptide 1 (AUCGLP-1) was associated with a high ΔWHtR (odds ratio [OR] = 0.796, P < 0.001), while a higher baseline AUCGLP-1 was associated with a high ΔWHtR in the patients treated with metformin (OR = 1.133, P = 0.025). Regarding the changes from baseline, an increase in AUCGLP-1 was associated with a high ΔWHtR in the acarbose (OR = 1.121, P = 0.016) but not metformin group. A higher reduction in high-density lipoprotein cholesterol/non-high-density lipoprotein cholesterol was also associated with a high ΔWHtR in the acarbose arm (OR = 20.735, P = 0.001). In the metformin arm, a higher reduction in fasting plasma glucose (OR = 0.843, P = 0.039) and total cholesterol was associated with a high ΔWHtR (OR = 0.743, P = 0.013). CONCLUSION: A lower glucagon-like peptide 1 level and higher increase in glucagon-like peptide 1 are associated with a high reduction in the WHtR in newly diagnosed Chinese diabetes patients receiving treatment with acarbose.

Liver X receptor ß increases aquaporin 2 protein level via a posttranscriptional mechanism in renal collecting ducts.

Liver X receptors (LXRs) including LXRα and LXRß are nuclear receptor transcription factors and play an important role in lipid and glucose metabolism. It has been previously reported that mice lacking LXRß but not LXRα develop a severe urine concentrating defect, likely via a central mechanism. Here we provide evidence that LXRß regulates water homeostasis through increasing aquaporin 2 (AQP2) protein levels in renal collecting ducts. LXRß-/- mice exhibited a reduced response to desmopressin (dDAVP) stimulation, suggesting that the diabetes insipidus phenotype is of both central and nephrogenic origin. AQP2 protein abundance in the renal inner medulla was significantly reduced in LXRß-/- mice but with little change in AQP2 mRNA levels. In vitro studies showed that AQP2 protein levels were elevated upon LXR agonist treatment in both primary cultured mouse inner medullary duct cells (mIMCD) and the mIMCD3 cell line with stably expressed AQP2. In addition, LXR agonists including TO901317 and GW3965 failed to induce AQP2 gene transcription but diminished its protein ubiquitination in primary cultured mIMCD cells, thereby inhibiting its degradation. Moreover, LXR activation-induced AQP2 protein expression was abolished by the protease inhibitor MG132 and the ubiquitination-deficient AQP2 (K270R). Taken together, the present study demonstrates that activation of LXRß increases AQP2 protein levels in the renal collecting ducts via a posttranscriptional mechanism. As such, LXRß represents a key regulator of body water homeostasis.

Enhanced pressor response to acute Ang II infusion in mice lacking membrane-associated prostaglandin E2 synthase-1.

AIM: To examine the contribution of vascular membrane-associated prostaglandin E2 synthase-1 (mPGES-1) to acute blood pressure homeostasis. METHODS: Angiotensin II (AngII, 75 pmol·kg⁻¹·min⁻¹) was continuously infused via the jugular vein into wild-type and mPGES-1(-/-) mice for 30 min, and blood pressure was measured by carotid arterial catheterization. RT-PCR and immunohistochemistry were performed to detect the expression and localization of mPGES-1 in the mouse arterial vessels. Mesenteric arteries were dissected from mice of both genotypes to study vessel tension and measure vascular PGE2 levels. RESULTS: Wild-type and mPGES-1(-/-) mice showed similar blood pressure levels at baseline, and the acute intravenous infusion of AngII caused a greater increase in mean arterial pressure in the mPGES-1(-/-) group, with a similar diuretic and natriuretic response in both groups. mPGES-1 was constitutively expressed in the aortic and mesenteric arteries and vascular smooth muscle cells of wild-type mice. Strong staining was detected in the smooth muscle layer of arterial vessels. Ex vivo treatment of mesenteric arteries with AngII produced more vasodilatory PGE2 in wild-type than in mPGES-1(-/-) mice. In vitro tension assays further revealed that the mesenteric arteries of mPGES-1(-/-) mice exhibited a greater vasopressor response to AngII than those arteries of wild-type mice. CONCLUSION: Vascular mPGES-1 acts as an important tonic vasodilator, contributing to acute blood pressure regulation.