Effects of acute starvation on insulin resistance in obese patients with and without type 2 diabetes mellitus

BACKGROUND & AIMS: Starvation decreases insulin sensitivity and glucose tolerance in both lean and obese (OB) non-diabetic subjects. Influence of drastic calorie reduction on insulin resistance in patient with type 2 diabetes (T2DM) is not known. METHODS: We enrolled 10 T2DM (diabetes duration 11.1+/-7.9 years) and 10 OB age and weight-matched subjects and performed isoglycaemic hyperinsulinaemic clamp (two 120 min phases of 60 and 120 mIU min-1 m-2 i.v. insulin) with indirect calorimetry at baseline and after 60 h of fasting. RESULTS: After starvation insulin-mediated glucose disposal decreased significantly in both hyperinsulinaemic phases in T2DM (phase 1: from 46+/-28 to 33+/-17, P<0.04; phase 2 from 122+/-47 to 80+/-30 microg kg-1 min-1, P<0.01) as well as in OB (phase 1: from 94+/-52 to 52+/-24, P<0.04; phase 2: from 131+/-46 to 106+/-43 microg kg-1 min, P<0.01). Both oxidative and non-oxidative components of glucose disposal tended to be reduced after fasting. A change of insulin sensitivity was found to be highly dependent upon pre-starvation conditions: more insulin resistant subjects tended to maintain (or modestly improve) insulin resistance whilst subjects with better insulin sensitivity tended to worse it. CONCLUSION: Insulin sensitivity worsens similarly in both T2DM and OB subjects during 60-h fast. The change is probably predictable according to pre-starvation insulin sensitivity.     

Metabolic response to a ketogenic breakfast in the healthy elderly

Objective  To determine whether the metabolism of glucose or ketones differs in the healthy elderly compared to young or middle-aged adults during mild, short-term ketosis induced by a ketogenic breakfast. Design and participants  Healthy subjects in three age groups (23±1, 50±1 and 76±2 y old) were given a ketogenic meal and plasma -hydroxybutyrate, glucose, insulin, triacylglycerols, total cholesterol, non-esterified fatty acids and breath acetone were measured over the subsequent 6 h. Each subject completed the protocol twice in order to determine the oxidation of a tracer dose of both carbon-13 (¹³C) glucose and ¹³C- -hydroxybutyrate. The tracers were given separately in random order. Apolipoprotein E genotype was also determined in all subjects. Results  Plasma glucose decreased and -hydroxybutyrate, acetone and insulin increased similarly over 6 h in all three groups after the ketogenic meal. There was no significant change in cholesterol, triacylglycerols or non-esterified fatty acids over the 6 h. ¹³C-glucose and ¹³C- -hydroxybutyrate oxidation peaked at 2–3 h post-dose for all age groups. Cumulative ¹³C-glucose oxidation over 24 h was significantly higher in the elderly but only versus the middle-aged group. There was no difference in cumulative 13C- -hydroxybutyrate oxidation between the three groups. Apolipoprotein E ( 4) was associated with elevated fasting cholesterol but was unrelated to the other plasma metabolites. Conclusion  Elderly people in relatively good health have a similar capacity to produce ketones and to oxidize ¹³C- -hydroxybutyrate as middle-aged or young adults, but oxidize ¹³C-glucose a little more rapidly than healthy middle-aged adults.     

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women

BACKGROUND: Breakfast consumption is recommended, despite inconclusive evidence of health benefits. OBJECTIVE: The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. DESIGN: In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. RESULTS: Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). CONCLUSION: OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.     

Hcy在2型糖尿病合并脂肪肝及高血压患者中的变化

目的:探讨血清同型半胱氨酸水平在2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)及高血压患者中的变化。方法:将130例新诊断T2DM患者分为单纯T2DM组22例,T2DM合并高血压(高血压)组32例,T2DM合并NAFLD(NAFLD)组36例,糖尿病合并NAFLD及高血压(NAFLD合并高血压)组40例。测定血清同型半胱氨酸(Hcy)、空腹C肽(FCP)和胰岛素(FINS)、游离脂肪酸(FFA)、血脂谱、尿酸和肌酐等水平,并计算胰岛素抵抗指数(HOMR-IR)及胰岛素敏感指数(ISI)。结果:130例新诊断T2DM患者中,NAFLD占59.2%,高血压占53.8%,NAFLD合并高血压占30.0%。NAFLD组与NAFLD合并高血压组患者血清甘油三酯和尿酸水平均高于单纯T2DM组患者(P<0.05),NAFLD组与NAFLD合并高血压组患者血清FFA和Hcy水平高于单纯T2DM组与高血压组患者(P<0.01)。NAFLD组与NAFLD合并高血压组患者LnHOMA-IR高于单纯T2DM组与高血压组患者(P<0.05),但是前者的LnISI却小于后者(P<0.05)。结论:Hcy、甘油三酯、FFA及胰岛素抵抗是2型糖尿病患者合并NAFLD和高血压的危险因素;T2DM合并NAFLD患者血清Hcy水平高于T2DM合并高血压的患者,而且胰岛素抵抗更为明显。     

Plasma resistin, insulin concentration in non-diabetic and diabetic, overweight/obese Thai

This study investigated levels of fasting plasma glucose (FBS), homeostasis model of the assessment of the insulin resistance (HOMA), lipid profile, insulin, and resistin hormones in 202 individuals, divided into four groups. Two groups had type II diabetes mellitus (DM): one group had been overnourished (DM/OB) (body mass index: BMI equal or above 25) and the other had not (DM/nOB). Two additional groups not suffering from diabetes were either overnourished (nDM/OB) or of normal nutritional status (nDM/nOB). Only the DM/OB group had insulin levels elevated above the other three groups. Resistin levels had been lowest in the nDM/nOB group. When participants of the two nOB groups were pooled into one group and the subjects of the two OB groups were combined into another group, the median plasma resistin levels of the OB groups were significantly higher compared with the nOB groups. Likewise the DM groups had higher resistin levels than the nDM groups. A significant correlation of plasma resistin with BMI, waist circumference, waist-to-hip ratio, FBS, and HOMA score had been observed. The result suggests that plasma resistin has a role in linking central obesity and obesity-related insulin resistance to type II diabetes mellitus.     

Pre-teen insulin resistance predicts weight gain, impaired fasting glucose, and type 2 diabetes at age 18-19 y: a 10-y prospective study of black and white girls

BACKGROUND: Identifying early pre-teen predictors of adolescent weight gain and the development of impaired fasting glucose (IFG) and type 2 diabetes (T2DM) at age 18-19 y could provide avenues for prevention. OBJECTIVE: We evaluated possible pre-teen predictors for development of IFG, T2DM, and changes in body mass index at age 18-19 y in black and white girls. DESIGN: In a prospective cohort study, body habitus and fasting insulin and glucose were measured at ages 9-10 and 18-19 y, and multiple 3-d diet records were collected. Factors predicting 10-y change in body mass index and development of IFG and T2DM together were assessed. RESULTS: In multivariate analyses, 10-y change in homeostatic model assessment of insulin resistance (HOMA-IR) and the age 9-10 y HOMA-IR x percentage of calories from fat interaction were positive predictors of 10-y changes in body mass index. At age 18-19 y, there were 5 incident cases of T2DM, 37 cases of IFG, and 597 noncases. Age 9-10 y IFG and HOMA-IR (or insulin), 10-y change in HOMA-IR (or insulin), and the age 9-10 y insulin x total caloric intake interaction predicted IFG and T2DM at age 18-19 y. CONCLUSIONS: Pre-teen IFG, insulin resistance (and insulin), and rapidly increasing insulin resistance during adolescence identifies girls who are at greater risk of future IFG and T2DM. In addition, insulin resistance, interacting with high-fat diets, identifies girls who are at risk of greater weight gain. These findings could open avenues to primary prevention of obesity, IFG, and T2DM in children.     

Skeletal muscle protein anabolic response to increased energy and insulin is preserved in poorly controlled type 2 diabetes

Type 2 diabetes (T2DM) subjects failing diet treatment are characterized by hyperinsulinemia and insulin resistance leading to fasting and postprandial hyperglycemia and hyperlipidemia. Energy is essential for allowing the process of protein synthesis to proceed. Additionally, insulin can stimulate protein synthesis in human muscle. The aims of this study were to determine if poorly controlled T2DM affects postabsorptive muscle protein anabolism, and if the muscle anabolic response to hyperinsulinemia with high energy availability is maintained. Control (n = 6) and T2DM subjects (n = 6) were studied in the postabsorptive state and during an isoenergetic high nutritional energy clamp (relative to postabsorptive state). Muscle protein synthesis and breakdown (nmol . min(-1) . 100 g leg muscle(-1)) were assessed using stable isotope methodology, femoral arterio-venous sampling, muscle biopsies, and a three-pool model to calculate protein turnover. Postabsorptive phenylalanine net balance and whole body rate of appearance (Ra) were not different between groups; however, basal muscle protein breakdown was higher in T2DM (94 +/- 9) than in controls (58 +/- 12) (P < 0.05) and muscle protein synthesis tended (P = 0.07) to be elevated in T2DM (66 +/- 14) compared with controls (39 +/- 6). During the clamp, net balance increased, whole body Ra and muscle protein breakdown decreased (P < 0.05), and muscle protein synthesis tended to decrease (P = 0.08) to a similar extent in both groups. We conclude that postabsorptive muscle protein turnover is elevated in poorly controlled T2DM, however, there is no excessive loss of muscle protein because net balance is not different from controls. Moreover, the anabolic response to increased insulin and energy availability is maintained in T2DM.     

2型糖尿病大血管病变与视黄醇结合蛋白4及高敏C反应蛋白关系的研究

目的 探讨2型糖尿病(T2DM)大血管病变患者血清视黄醇结合蛋白4(RBP4)及高敏C反应蛋白(hs-CRP)水平的变化.方法 入选研究对象115例,其中单纯T2DM组40例,T2DM大血管病变(病变T2DM)组40例,对照组35例.检测其空腹血清RBP4、hs-CRP,同时测空腹血糖(FBG)、身高、体重、空腹胰岛素(FINS)、糖化血红蛋白(HbA1c)、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆同醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),计算体重指数(BMI)和稳态模型评估法胰岛素抵抗指数(HOMA-IR).分析三组RBP4水平的变化,及其与上述其他指标的相关性.结果 hs-CRP、RBP4在病变T2DM组和单纯T2DM组显著高于对照组[hs-CRP分别为(9.12±4.21)、(2.01±1.96)、(0.98±0.36)mg/L,RBP4分别为(30.10±5.45)、(20.02±5.32)、(12.02±3.45)mg/L](P<0.01),病变T2DM组显著高于单纯T2DM组(P<0.01).单因素相关分析显示RBP4与LDL-C、BMI、FBG、hs-CBP、FINS、HOMA-IR呈正相关(相关系数分别为0.325、0.597、0.323、0.571、0.275、0.463,P<0.05或<0.01).结论 血清RBP4、hs-CRP在糖尿病患者中显著升高,其水平变化与糖尿病大血管并发症的发生、发展密切相关.     

Extended effects of evening meal carbohydrate-to-fat ratio on fasting and postprandial substrate metabolism

BACKGROUND: High-fat and high-carbohydrate diets lead to insulin resistance, gastrointestinal adaptation, and high plasma triacylglycerol concentrations. It is unclear, however, how rapidly these changes occur. OBJECTIVE: We sought to determine the effects of both high-fat and high-carbohydrate evening meals on parameters of insulin resistance, hypertriglyceridemia, and gastrointestinal hormones. DESIGN: Twelve healthy men were studied on 4 separate occasions. On 2 occasions, the subjects received a high-fat evening meal (62% of energy from fat) and on the other 2 occasions the subjects received a low-fat evening meal (16% of energy from fat). The morning after each meal the subjects were administered either an oral-fat-tolerance test or an oral-glucose-tolerance test. Plasma samples were analyzed for glucose, insulin, fatty acids, 3-hydroxybutyrate, triacylglycerol, pancreatic polypeptide, peptide YY, and cholecystokinin. Postchallenge data were analyzed by two-way analysis of variance with interaction and fasting concentrations analyzed by repeated-measures analysis of variance. RESULTS: Fasting plasma concentrations of triacylglycerol were significantly elevated 12 h after each evening meal, but fatty acid and 3-hydroxybutyrate concentrations were reduced. No effects on glucose or insulin concentrations were detected. The high-fat evening meals elevated plasma cholecystokinin concentrations, reduced fasting concentrations of pancreatic polypeptide, and had no significant effect on peptide YY concentrations. The ratio of fat to carbohydrate in the evening meal produced significant effects on plasma triacylglycerol and fatty acids during both the oral-fat-tolerance and oral-glucose-tolerance tests. CONCLUSIONS: The present study showed that the effects of high-fat and high-carbohydrate evening meals persist at least overnight and suggests that knowledge of recent dietary history is essential to the effective design of metabolic studies.     

Short-term ingestion of Ginkgo biloba extract does not alter whole body insulin sensitivity in non-diabetic, pre-diabetic or type 2 diabetic subjects--a randomized double-blind placebo-controlled crossover study

BACKGROUND & AIMS: Ingestion of Ginkgo biloba Extract (EGb 761) may increase pancreatic beta-cell function in both healthy subjects with normal glucose tolerance (NGT) as well as patients with Type 2 Diabetes mellitus (T2DM). Since hyperinsulinemia is a hallmark of T2DM, it is important to verify that increased insulin production is not due to increased insulin resistance. METHOD: NGT subjects (n = 10; age, 44.2 +/- 13.9 years old), impaired glucose tolerance (IGT) (n = 8; age 51.3 +/- 6.6 years old) and T2DM subjects (n = 8, 51.6 +/- 15.2 years old) completed a randomized, double-blind, placebo-controlled crossover study. After ingesting either EGb 761 (120 mg/day as a single dose) or placebo during each 3-month arm, a 2-step euglycemic insulin clamp was performed. RESULTS: At the low insulin infusion rate (10 mU/m2/min) the glucose metabolic rates (M values) were 3.5 +/- 1.5 vs. 3.0 +/- 0.5 mg/kg (P = 0.16), 3.0 +/- 0.4 vs. 2.8 +/- 0.8 mg/kg (P = 0.19) and 2.6 +/- 0.7 vs. 2.4 +/- 0.5 mg/kg (P = 0.09) for the placebo and EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. At the high insulin infusion rate (40 mU/m2/min) the M values were 7.3+/-2.3 vs. 8.1 +/- 2.5mg/kg (P = 0.07), 6.2 +/- 1.6 vs. 6.5 +/- 2.1 mg/kg (P = 0.32) and 3.6 +/- 1.6 vs. 3.5 +/- 1.0 mg/kg (P = 0.34) for placebo vs. EGb 761 cycles, in the NGT, IGT and T2DM subjects, respectively. CONCLUSION: The ingestion of 120 mg of EGb 761 as a single for 3 months did not produce insulin resistance in the non-diabetic or pre-diabetic subjects or exacerbate the disease in the T2DM subjects.     

2型糖尿病患者血清脂联素与炎症因子的相关性研究

目的探讨2型糖尿病患者血清脂联素与炎症因子的相关性,并观察抗炎药物对糖尿病患者的疗效。方法将我院门诊及住院2型糖尿病(T2DM)患者分为T2DM无大血管并发症患者(无病变组)55例及T2DM合并大血管病变患者(病变组)45例,以健康人30例为对照组。分别检测各组FPG、胰岛素、糖化血红蛋白、血脂、游离脂肪酸、血清CRP、脂联素、瘦素及肿瘤坏死因子TNF-α;并计算体质指数、腰臀比、胰岛素敏感性指数及胰岛素抵抗指数。T2DM患者均予抗炎治疗,并观察1年后检测以上指标。结果①T2DM患者血清脂联素、炎症因子及其他相关指标均与健康人有统计学差异,而且病变组较无病变组,WHR、FPG、HbA1C、FFA、CRP、Leptin及TNF-α显著升高及APN显著降低。②APN水平与BMI、FFA、WHR、FBG、HbA1C、HOMA-IR、CRP及TNF-α呈显著负相关。多元逐步回归分析显示APN与CRP、TNF-α、WHR及HbA1C呈显著相关。③予抗炎治疗1年后,患者FPG、FINS、HOMA-IR、TNF-α、CRP、FFA明显降低,ISI、APN增加。结论APN是T2DM和动脉粥样硬化的保护性因子,其作用的发挥是通过拮抗炎症因子实现的。干预炎症过程的长期药物治疗,将成为改善IR、治疗T2DM的新趋向。     

Reduction of plasma leptin concentrations by arginine but not lipid infusion in humans

OBJECTIVE: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. RESEARCH METHODS AND PROCEDURES: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A(1c); 7.3 +/- 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 +/- 0.7%), and nondiabetic subjects (CON; 5.4 +/- 0.1%). RESULTS: Fasting plasma leptin correlated linearly with body mass index among all groups (r = 0.61, p = 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p < 0.05) and CON (p < 0.01). Plasma leptin decreased within 30 minutes by approximately 11% in DM1 (p < 0.001), DM2 (p < 0.01), and CON (p < 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 +/- 0.1 mM) and DM2 (0.6 +/- 0.1 mM) than in CON (0.4 +/- 0.1 mM, p < 0.05) and transiently declined by approximately 50% (p < 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin ( approximately 35 pM) -glucagon ( approximately 90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by approximately 25% (p < 0.05) during 540 minutes without any difference between the high and low FFA conditions. DISCUSSION: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.     

Adipocyte differentiation-related protein in human skeletal muscle: relationship to insulin sensitivity

OBJECTIVE: To determine whether adipocyte differentiation-related protein (ADRP), a lipid droplet-associated protein that binds to and sequesters intracellular fatty acids, is 1) expressed in human skeletal muscle and 2) differentially regulated in human skeletal muscle obtained from obese non-diabetic (OND) and obese diabetic (OD) subjects. RESEARCH METHODS AND PROCEDURES: Ten OND subjects and 15 OD subjects underwent a weight loss or pharmacological intervention program to improve insulin sensitivity. Anthropometric data, hemoglobin A(1C), fasting glucose, lipids, and glucose disposal rate were determined at baseline and at completion of studies. Biopsies of the vastus lateralis muscle (SkM) were obtained in the fasting state from OND and OD subjects. Protein expression was determined by Western blotting. RESULTS: ADRP was highly expressed in SkM from OND (4.4 +/- 1.54 AU/10 microg, protein, n = 10) and OD (5.02 +/- 1.33 AU/10 microg, n = 12) subjects. OND subjects undergoing weight loss had decreased triglyceride levels and improved insulin action. SkM ADRP content increased with weight loss from 5.14 +/- 2.15 AU/10 microg to 9.92 +/- 1.57 AU/10 microg (p < 0.025). OD subjects were treated with either troglitazone or metformin, together with glyburide, for 3 to 4 months. Both treatments attained similar levels of glycemic control. OD subjects with lower baseline ADRP content (2.85 +/- 1.07 AU/10 microg, n = 6) displayed up-regulation of ADRP expression (to 9.27 +/- 2.76 AU/10 microg, p < 0.025). DISCUSSION: ADRP is the predominant lipid droplet-associated protein in SkM, and low ADRP expression is up-regulated in circumstances of improved glucose tolerance. Up-regulation of ADRP may act to sequester fatty acids as triglycerides in discrete lipid droplets that could protect muscle from the detrimental effects of fatty acids on insulin action and glucose tolerance.     

Glucose tolerance and skeletal muscle gene expression in response to alternate day fasting

OBJECTIVE: Alternate day fasting may extend lifespan in rodents and is feasible for short periods in nonobese humans. The aim of this study was to examine the effects of 3 weeks of alternate day fasting on glucose tolerance and skeletal muscle expression of genes involved in fatty acid transport/oxidation, mitochondrial biogenesis, and stress response. RESEARCH METHODS AND PROCEDURES: Glucose and insulin responses to a standard meal were tested in nonobese subjects (eight men and eight women; BMI, 20 to 30 kg/m(2)) at baseline and after 22 days of alternate day fasting (36 hour fast). Muscle biopsies were obtained from a subset of subjects (n = 11) at baseline and on day 21 (12-hour fast). RESULTS: Glucose response to a meal was slightly impaired in women after 3 weeks of treatment (p < 0.01), but insulin response was unchanged. However, men had no change in glucose response and a significant reduction in insulin response (p < 0.03). There were no significant changes in the expression of genes involved in mitochondrial biogenesis or fatty acid transport/oxidation, although a trend toward increased CPT1 expression was observed (p < 0.08). SIRT1 mRNA expression was increased after alternate day fasting (p = 0.01). DISCUSSION: Alternate day fasting may adversely affect glucose tolerance in nonobese women but not in nonobese men. The gene expression results indicate that fatty acid oxidation and mitochondrial biogenesis are unaffected by alternate day fasting. However, the increased expression in SIRT1 suggests that alternate day fasting may improve stress resistance, a commonly observed feature of calorie-restricted rodents.     

FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women

BACKGROUND: A common functional missense mutation [Ala54Thr of the fatty acid-binding protein 2 gene (FABP2)] has previously been studied for associations with glucoregulation, postprandial lipemia, and lipid oxidation rates. However, most of those studies have not accounted for the interactive and potentially confounding effects of habitual physical activity and diet. OBJECTIVE: We tested the hypothesis that, in sedentary nondiabetic subjects following a low-fat diet, Thr54 FABP2 carriers have lower glucoregulatory function, greater postprandial lipemia, and greater lipid oxidation rates than do their Ala54 FABP2-homozygous counterparts. DESIGN: Men and women (n = 122) aged 50-75 y who were following a low-fat diet were genotyped and underwent oral-glucose-tolerance tests. A subgroup (n = 36) also underwent postprandial lipemia tests with lipid oxidation rate measurements. RESULTS: Thr54 carriers were less likely to have normal glucose tolerance (P = 0.05) and had higher fasting glucose concentrations (P = 0.003) than did Ala54 homozygotes. In Thr54 carriers, the insulin sensitivity index was lower (P = 0.02), and the fasting insulin and the oral-glucose-tolerance test insulin area under the curve were higher (P = 0.05 and 0.03, respectively) than in Ala54 homozygotes. FABP2 genotype was not associated with fasting or postprandial lipemia test triacylglycerol or free fatty acids (P > or = 0.22 for all), but postprandial lipid oxidation rates were higher (P = 0.01), which suggests that fat absorption is higher in Thr54 carriers than in Ala54 homozygotes. CONCLUSIONS: In sedentary nondiabetic persons following a low-fat diet, FABP2 Thr54 carriers have lower glucose tolerance and lower insulin action than do Ala54-homozygous persons. Furthermore, FABP Thr54 carriers have higher lipid oxidation rates, which may be the mechanism of glucoregulatory dysfunction.     

2型糖尿病患者视黄醇结合蛋白4与炎症因子、脂代谢及胰岛素抵抗的相关分析

目的探讨RBP-4对与2型糖尿病患者炎症因子超敏C反应蛋白（hs—CRP）、脂代谢及胰岛素抵抗的关系。方法105例门诊初诊患者及同期门诊或体检中心健康体检者,正常葡萄糖耐量（NGT）组34例和T2DM组71例,按BM1分为正常体重组（NW）56例及超重／肥胖组（OW／OB）49例。用ELISA测定血清RBP-4。全自动生化仪检测hs—CRP、游离脂肪酸（FFA）、甘油三酯（TG）、总胆固醇（Tc）;化学发光法检测胰岛素。结果T2DM组ln（HOMA—IR）、TG、FFA、In（hs—CRP）均高于NGR组[1．20±0．38VS0．76±0．34,（2．74±2．20）mmol／L vs（1．88±1．41）mmol／L,（0．80±0．29）mmol／L vs（0．61±0．22）mmol／L,0．62±1．00 vs -0．17±1．07],差异有统计学意义。单因素简单相关分析显示,NGR组lnRBP-4与In（HOMA-IR）存在正相关（r=0．382,P〈0．05）,与TC、TG、FFA、in（hs．CRP）无关。T2DM组,lnRBP-4与FFA、In（hs—CRP）呈正相关（r=0．242,P〈0．05;r=0．346,P〈0．01）,但与in（HOMA—IR）、TC、TG均无相关性。NW组,lnRBP-4与ln（HOMA—IR）、TC、TG、FFA、ln（hs-CRP）均无相关性。而OW／OB组,lnRBP-4与ln（HOMA—IR）、In（hs—CRP）呈正相关（r=0．290,0．295,P〈0．05）,但与TC、TG、FFA无关。逐步多元线性回归分析显示,各组的ln（hs—CRP）、TC、TG、FFA、in（HOMA—IR）均非lnRBP-4的独立影响因素。结论在T2DM患者中,RBP-4与ln（hs．CRP）、FFA正相关,可作为一新的炎症标志物。     

PAI-1与2型糖尿病动脉粥样硬化病变的研究

目的探讨2型糖尿病动脉粥样硬化病变与血浆纤溶酶原激活物抑制物1（PAI-1）之间的关系。方法选取34例正常对照组，134例2型糖尿病患者，按有无大血管并发症及体重指数（BMI）分为4个亚组，采用酶联免疫吸附法测定其纤溶酶原激活物抑制物1（PAI-1）的水平。结果4个糖尿病亚组与对照组PAI-1水平相比差异有显著性，糖尿病并发大血管病变组较糖尿病未合并大血管病变组的PAI-1水平差异有显著性（P＜0．01）。肥胖合并大血管病变组较肥胖无大血管病变组相比PAI-1有明显差别（P＜0．05）；简单相关分析显示PAI-1与BMI、WHR、FFA、TCH、FINS呈正相关，多元回归分析显示BMI、FINS作为独立因素影响PAI-1水平。结论2型糖尿病合并大血管病变及肥胖患者PAI-1水平升高，PAI-1水平可能与糖尿病大血管病变有关。     

Closing the gap between literature and practice: evaluation of a teaching programme (in the absence of a structured treatment) on both type 1 and type 2 diabetes

Athough education is considered an integral part of diabetes management, it remains low in the practical priorities of clinicians. We performed the first structured educational intervention in a diabetic outpatient department, where patients were controlled with no provider autonomy support available. We recruited 77 Type 1 (T1DM) and 154 Type 2 diabetic (T2DM) patients as well as 87 matched control subjects. Baseline evaluation included: medical interview; questionnaires concerning diabetes knowledge, diabetes quality of life, state-trait anxiety, depression and general perceived self-efficacy; biochemical examination (fasting blood glucose, HbA1c, lipids, uric acid, urinary glucose and albumin excretion). Of the 231 diabetic patients, 154 agreed to attend an educational course, yet only 101 patients (37 T1DM and 64 T2DM) completed it (intervention group) due to organisational barriers. Intervention and reference (non-participant patients) groups received identical medical care, except that the educational group met with the educator during five teaching sessions. Three to six months after the completion of the course, they underwent a final assessment. Prospective results were: 1) in T1DM, a reduction in HbA1c levels and an increase in plasma HDL cholesterol with no change in drug treatment (the reference group showed no change in HbA1c values despite an increased insulin dose), improved technical skill, knowledge, quality of life and self-efficacy; 2) in T2DM, a reduction in fasting plasma glucose and an improvement in knowledge and quality of life. Analysis of the cross-sectional data at baseline evidenced: 3) the same levels of anxiety, depression and general self-efficacy in diabetic patients compared with healthy control subjects; 4) lower diabetes-specific quality of life associated with established insulin treatment in T2DM; 5) significant gender differences among healthy as well as diabetic subjects in degree of psychological distress. Education by itself is more than simply offering information to people (even in a troubled context) and its infrequent incorporation in practice really contradicts resource efficiency.     

Effect of taurine treatment on insulin secretion and action, and on serum lipid levels in overweight men with a genetic predisposition for type II diabetes mellitus

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) is increasing with an epidemic growth rate. Animal studies with taurine supplementation have shown increased insulin secretion and action, suggesting that taurine supplementation may have a potential to prevent T2DM. OBJECTIVE: To assess the effect of taurine treatment on insulin secretion and action, and on plasma lipid levels in overweight men with a positive history of T2DM. DESIGN: 20 nondiabetic subjects were included in a double-blinded, randomized, crossover study, receiving a daily supplementation of 1.5 g taurine or placebo for two periods of 8 weeks. The subjects were overweight first-degree relatives of T2DM patients. An intravenous glucose tolerance test (IVGTT) was used to measure first-phase insulin secretory response, and a euglycemic hyperinsulinemic clamp was used to determine peripheral insulin action. RESULTS: Mean plasma taurine concentration was 39 +/- 7 (s.d.) micromol/l after placebo and 131 +/- 62 micromol/l after taurine intervention (P < 0.0001). There was no significant difference after taurine intervention compared to placebo in incremental insulin response (Insincr.) neither during the IVGTT, nor in insulin-stimulated glucose disposal during the clamp. Insulin secretion, adjusted for insulin sensitivity, was also unchanged. There was no significant effect of taurine supplementation on blood lipid levels as well. CONCLUSION: Daily supplementation with 1.5 g taurine for 8 weeks had no effect on insulin secretion or sensitivity, or on blood lipid levels. These findings in persons with an increased risk of T2DM are in contrast to those from animal studies, and do not support the assumption that dietary supplementation with taurine can be used to prevent the development of T2DM.     

甘精胰岛素用于Ⅱ型糖尿病患者术后血糖控制的探讨

目的:探讨甘精胰岛素用于II型糖尿病患者手术后血糖控制的可行性。方法:选择51例接受外科手术后的II型糖尿病患者,分为甘精胰岛素治疗组(LAN组)16例,常规生物合成人胰岛素治疗组(MSII组)19例,胰岛素泵治疗组(CSII组)16例。LAN组患者术后使用甘精胰岛素,视空腹血糖变化情况调整其剂量,患者如进食则于餐前给予短效胰岛素。MSII组术后用静脉胰岛素输注,患者进食后可逐渐采用传统胰岛素强化治疗方案(R+R+R+NPH)。CSII组每天24 h持续泵入短效胰岛素,禁食期只给予基础量,进食后给予基础和餐时量。观察各组患者治疗前后血糖变化、胰岛素用量、低血糖发生率及术后并发症发生率,酮症发生率。结果:各组治疗后血糖均明显低于治疗前,LAN组治疗后血糖低于MSII组,与CSII组无明显差异;LAN组低血糖发生率低于MSII组,而与CSII比较无显著性差异。结论:II型糖尿病患者术后禁食或进食不规律阶段,使用常规胰岛素治疗,血糖波动较大且患者依从性差;甘精胰岛素在糖尿病患者手术后降糖效果显著,能迅速、平稳控制血糖且患者依从性好,是一种安全、有效且患者易接受的用于II型糖尿病患者术后治疗的药物。