Objective:This study was attempted to determine the effects of marine collagen peptides(MCPs) on glucose and lipid metabolism and markers of three metabolic nuclear receptors,peroxisome prolifera tor-activated receptor (PPARs), liver X receptor (LXRs)and farnesoid X receptor (FXRs), in hypertensive patients with type 2 diabetes.Methods:The study population consisted of one hundred hypertensive patients with type 2 diabetes and fifty healthy subjects recruited from local communities in Shenzhen, China.Dia betic patients with hypertension were randomized into intervention group(n=50, group A)and non-interven tion group (n=50, group B)whereas fifty healthy subjects were assigned to control group.MCPs or placebo (water-soluble starch)were respetively given to group A and group B before breakfast and bedtime at a dose of 6.5g over a period of three months.Fasting serum samples were analyzed for levels of blood glu cose, insulin, serum lipid, uric acid, glycosylated hemoglobin (GHbAlc), high sensitivity C-Reactive pro tein (hs-CRP), serum creatinine and markers of metabolic nuclear receptor,including free fatty acid, cy tochrome P450,1eptin,resistin, adiponectin,bradykinin,NO and prostacyclin before intervention, 1.5 months, and 3 months after intervention.New occurrence of acute or chronic complications developed dur ing the study such as hypoglycemia and diabetic ketoacidosis were recorded and compared among different groups.Results : Before intervention, the levels of fasting blood glucose, insulin, triglyceride in group A and B were higher than those of healthy controls while levels of HDLc in group A and group B were much low er than that of healthy controls.Throughout the study,the concentrations of free fatty acid,cytochrome P450, resistin and bradykinin in group A and B were much higher than those in controls, yet no statistical differences were noted between group A and B.Levels of prostacyclin in group A and B were higher than those of normal controls either before or after intervention.After treated with MCPs or placebo for 1.5 months and 3 months, levels of fasting blood glucose,insulin, TG, TC, LDLc, flee fatty acid, leptin, re sistin,hs-CRP,and GHbAlc all declined whereas levels of HDLc and adiponectin increased in group A.However, levels of fasting blood glucose,insulin, TG, TC, LDLc, free fatty acid, leptin, resistin, and GH-bAlc increased whereas levels of HDLc decreased in group B and healthy controls.After treated with MCPs, the leptin level decreased in group A but increased significantly in group B and healthy controls.Re sistin levels decreased in group A but increased significantly in group B.Adiponectin levels increased in group A but decreased in healthy controls and group B,yet exhibiting no significant difference.Three months after MCP treatment, the levels of bradykinin increased significantly in group A.In contrast, levels of bradykinin in group B decreased significantly three months after intervention, prostacyclin levels signifi cantly increased in group B and healthy controls but decrease in group A.Addition, in group A, MCP treat ment caused marked reduction of GHbAlc in a time-dependant manner.In contrast,in group B, levels of GHbA1 c increased dramatically three months after treatment with placebo.Furthermore, there were no new cases of diabetes or hypertension in healthy controls.Three and eight cases of hypoglycemia at night in group A and B were observed respetively.One case in group B was hospitalized due to ketoacidosis.No new chronic complications of diabetes occurred in three groups.Conclusions:Our study shows that MCPs could reduce the levels of fasting blood glucose, TG, TC, LDLc, fi:ee fatty acid, cytochrome P450 and uric acid and increase HDLc levels in hypertensive patients with type 2 diabetes,thus improving glucose and lipid protile in hypertensive patients with type 2 diabetes.Moreover, our study also finds MCP administra tion led to decrease of leptin, resistin, and prostacyclin and increase of adiponectin and bradykinin, all of which are important players in diabetic and hypertension pathogenesis.As evidenced in our present study, supplement of MCPs before bedtime may reduce risk of hypoglycemia risk at night.Regulation on metabol ic nuclear receptors by MCPs may be the possible underlying mechanism for its observed effects in the study.Further study into its mode of action may shed new light on development of new drugs based on bioactive peptides from marine sources.