1.Lifestyle Or Pioglitazone Intervention On Insulin Resistance And β Cell Function In Nondiabetic Subjects With Hypertriglyceridaemia--a Two-year-prospective Study On Lipotoxicity 2.Efficacy And Safety Comparison Of Basal Insulin Or Premixed Insulin Twic

OBJECTIVE—To explore the effects and strategies of lifestyle or/and pioglitazone intervention on lipotoxicity.RESEARCH DESIGN and METHODS—Nondiabetic subjects with hypertriglyceridaemia(TG 2.26-4.52mmol/L) were randomly assigned to receive one tablet of placebo(CON) or diet and exercise education plus one tablet of placebo(LIF),or diet and exercise education plus 15 mg/day pioglitazone(PIO) for 24months.Before and during the intervention,body composition,body fat distribution[waist circumference(WR),waist-to-hip ratio(WHR)],plasma adiponectin,plasma TNF-α,urine albumin/creatine ratio(UACR),insulin sensitivity andβcell function were assessed.RESULTS—We enrolled 97subjects in this study[baseline data:BMI 26.8±3.1 kg/m²,WHR 0.97±0.04,FFA 0.5mmol/L(0.4—0.7),TG 2.93mmol/L(2.51—3.49)], 66subjects completed this 2-year study.At the end of the second year,compared with CON group,FFA in PIOgroup were significantly lower[0.30mmol/L(0.20-0.45) vs 0.43mmol/L(0.40-0.59);P＜0.05];WR and WHR decreased larger;plasma adiponectin were higher[7216ng/ml(4234～9261) vs 3882ng/ml(2654～5746);P＜0.05];plasma TNF—αwere lower(6.38pg/ml(3.32～8.26) vs 12.87pg/ml(9.16～20.31),P＜0.01), UACR were lower(0.31mg/mmol(0.10～0.91) vs 2.28 mg/mmol(1.12～4.01), P＜0.01),HOMA—IR increment from baseline were smaller(0.08±0.33 vs 1.20±0.38,P＜0.05),early insulin secretion response increased larger(0.5h—insulin in OGTT:102.40±14.49uiu/ml vs 68.13±7.65 uiu/ml, iNS(30-0)min/BG(30-0)min(IGR):24.67±3.63 vs 14.16±2.05;all P＜0.05)。The decrease in plasma FFA was strongly and independently associated with IGR2y.Some of the above parameters ameliorated in LIF group,but the degree was limited and couldn't last very long. CONCLUSIONS—We show for the first time that pioglitazone used in nondiabetic subjects with hypertriglyceridaemia can decrease FFA by improving adipose tissue function,induce increase in serum adiponectin,decrease in TNF-αand UACR.All these factors contribute to amelioration of insulin resistance andβcell function.And may predict the reduction in incidence of diabetes and risk of future cardiovascular disease. OBJECTIVE- To compare the efficacy and safety of glargine or premixed insulin twice daily in combination with glimepiride in Type 2 Diabetes.RESEARCH DESIGN AND METHODS-In a 12-week,two-center,open,parallel group clinical trial,80 type 2 diabetic patients treated with twice-daily premixed 30R insulin with or without OAD(s)(fasting blood glucose[FBG]7.8 mmol/L～16.7mmol/L,HbA1c7%～10%) were randomized to once-daily morning insulin glargine plus glimepiride 3mg or premixed 30R insulin(70/30) twice-daily plus glimepiride 3mg.Insulin dosage was titrated to target FBG≤6.0mmol/L using a three-day forced-titration algorithm.RESULTS-Mean HbA1c reduction from baseline were similar in glargine group and premixed insulin group(8.8%→8.0%vs 8.9%→7.8%,P=NS).However, hypoglycemic episodes were significantly higher in premixed-insulin-treated subjects than in glargine-treated subjects,(total:123 vs 57;proved hypoglycemic episodes (94(76%) vs 21(47%),χ²=23.692 P＜0.001),The frequency of hypoglycemia before lunch was especially greater in premixed-insulin-treated subjects(64(52%) vs 17(30%)χ²=7.762 P=0.005).Several subjects from the premixed arm experienced too frequent hypoglycemic episodes to be recorded during 10AM～11AM almost every day.Subgroup analysis for patients treated with glargine:28.2%(11 cases) of the patients in this subgroup attained HbA1c≤7.5%.Mean daily dosage for glargine at 12w were 0.58±0.29 u.kg^-1.d^-1 in this subgroup.23.1%(9 cases) patients with HbA1c＞8.5%,mean daily dosage for glargine were 0.66±0.30 u.kg^-1.d^-1 at 12w. There were significant differences of baseline HbA1c,diabetes duration and baseline postprandial C-peptide between the two subgroups in glargine arm(HbA1c:8.1%±0.8%vs 9.6%±1.2%;duration:10years(6～14.5) vs 13years(8～19.5);postprandial c peptide:2.5nmol/L(1.4～3.3) vs 1.4nmol/L(1.2～2.6),all P＜0.05).CONCLUSIONS-Some type 2 diabetic patients treated with twice-daily injection of 70/30 with or without OAD(s) can be effectively and safely switched to basal insulin plus OAD.Pretreatment HbA1c,diabetes duration and postprandial C peptide are the key factors that closely related to efficacy of this new regimen.