Low-grade systemic inflammation, hypoadiponectinemia and a high concentration of leptin are present in very young obese children, and correlate with metabolic syndrome

OBJECTIVE: To determine the concentration levels of C-reactive protein (CRP), leptin and adiponectin in obese pre-pubertal children, and their possible relation with metabolic syndrome, fibrinogen and plasminogen activator inhibitor-1. METHODS: A study was carried out in 51 obese children (aged 6 to 9 years) and the same number of non-obese children (control group), matched by age and sex. (Cross-sectional study of obese children). Body mass index (BMI), waist/hip ratio (WHR) and blood pressure were determined for each child. Serum CRP, leptin, adiponectin, glucose, insulin, lipid profile, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen were all measured. RESULTS: The levels of CRP serum (1.67+/-0.222 vs 0.92+/-0.16 mg/l) and leptin (15.56+/-1.27 vs 4.68+/-0.62 ng/ml) were significantly higher in obese children. The adiponectin level was significantly higher in non-obese children (11.58+/-0.63 vs 9.64+/-0.49 microg/dl). In the obese group, log. CRP showed a positive correlation with BMI, insulin, homeostasis model assessment (HOMA), triglycerides, alanine aminotransferase (ALT), uric acid, PAI-1, fibrinogen and interleukin 6 (IL-6), and correlated negatively with apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C). The leptin was positively correlated with BMI, insulin, HOMA, triglycerides and PAI-1 and negatively with Apo A-I and HDL-C. Adiponectin correlated negatively with BMI, insulin, HOMA, and triglycerides. CONCLUSIONS: Low-grade systemic inflammation, elevated leptin concentration and low adiponectin level are described in very young obese children, correlating with a range of variables of metabolic syndrome. Inflammation and adipocytokines can play an important role in the etiopathogeny of metabolic syndrome.     

肥胖者胰岛素分泌功能对糖耐量低减及糖尿病发生的影响

目的　探讨肥胖者胰岛素分泌变化对糖耐量低减 (IGT)及糖尿病 (DM)发生的影响。　方法　对 30例单纯性肥胖 [体重指数 (BMI) >2 7]患者进行血糖和胰岛素测定 ,并观察胰岛细胞分泌指数 (HOMA- IS)及胰岛素敏感性指数 (IAI) ,并对这些患者进行 15年随访。　结果　肥胖者空腹胰岛素 (FINS)水平明显高于正常人 (P <0 .0 1) ,与 HOMA - IS明显的正相关 (P <0 .0 1) ;空腹血糖(FPG)与 HOMA- IS及 IAI呈明显的负相关 (P<0 .0 1)。15年内 6 3.3%的肥胖者发展成 IGT,5 0 .0 %的肥胖者及发展成 IGT者发展为 2型 DM。　结论　肥胖对 IGT及糖尿病的发生、发展有着明显的影响 ,控制体重是减少 IGT发生的重要环节。     

Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children

Several methods have been developed to assess insulin resistance (IR), insulin secretion, and sensitivity: some of them, such as the homeostasis model assessment (HOMA) for IR (HOMA IR) and for insulin secretion (HOMA beta cell) and the quantitative insulin sensitivity check index (QUICKI) are based on fasting levels of glucose (fasting G) and insulin (fasting I); others, such as the pancreatic insulin response to glucose (IRG) and the insulin sensitivity index (ISI) are derived from the glycemic and insulinemic responses to the oral glucose tolerance test (OGTT). The aim of the study was to compare these indexes in a large group of prepubertal and pubertal obese subjects and verify whether the data from fasting samples were enough for evaluating IR and insulin secretion or if OGTT was mandatory. A total of 405 obese subjects (221 boys and 184 girls) was studied. Ninty-three were prepubertal (Tanner stage I), 98 early pubertal (stage II to III) and 214 late pubertal (stage IV to V). In each subject, a 120-minute OGTT was performed, and the glycemic (mean blood glucose [MBG]) and insulinemic (mean serum insulin [MSI]) responses, expressed as AUC/120, as well as IRG and ISI were calculated. The fasting I/fasting G ratio (FIGR), HOMA IR, HOMA beta cell, and QUICKI were then measured. FIGR and HOMA IR increased in both sexes during puberty, but in girls, the increase was already evident from stage I to stage II to III, while in boys, it was evident only from stage II to III to stage IV to V. QUICKI decreased in girls at the onset of puberty and was lower than in boys in stage II to III; on the other hand, HOMA beta cell did not show any variation. IRG increased throughout puberty, although it was higher in boys than in girls in stages II to III and IV to V, while ISI decreased at the onset of puberty in boys; HOMA IR correlated with MSI and IRG, and HOMA beta cell with MSI in pubertal subjects only. In conclusion, the indexes deriving from fasting samples, such as FIGR and HOMA IR, proved to be enough for evaluating IR in prepubertal and pubertal obese subjects, as did QUICKI for insulin sensitivity, However, OGTT is still useful for assessing insulin secretion, because IRG is more sensitive in depicting the pubertal variations of IR than HOMA beta cell.     

利拉鲁肽对RNAi介导的脂联素基因抑制ApoE基因敲除小鼠糖脂代谢的影响

目的 探讨利拉鲁肽对脂联素基因表达缺陷的ApoE基因敲除(ApoE-/-)小鼠糖脂代谢的影响.方法 采用静脉葡萄糖耐量试验(IVGTT)评价利拉鲁肽的量效关系.利用扩展高胰岛素钳夹技术评价各组小鼠糖脂代谢和胰岛素敏感性变化.结果 在IVGTT中,利拉鲁肽1 mg/kg组,糖负荷后5、15和30 min血糖值均明显低于其它剂量组(均P＜0.01),而血浆胰岛素水平在5、15 min均明显高于其他3组(均P＜0.01).联合注射利拉鲁肽和脂联素RNAi腺病毒组体重、空腹血糖、血浆游离脂肪酸、总胆固醇、甘油三酯、血浆胰岛素和低密度脂蛋白胆固醇(LDL-C)水平显著低于脂联素RNAi腺病毒组(P＜0.05或P＜0.01),而高密度脂蛋白胆固醇(HDL-C)则明显高于脂联素RNAi组(P＜0.05).钳夹稳态时,脂联素RNAi组血浆胰岛素明显高于利拉鲁肽组(P＜0.01),游离脂肪酸、总胆固醇、甘油三酯虽被抑制,但仍明显高于利拉鲁肽组(P＜0.05).利拉鲁肽组葡萄糖输注率(GIR)则明显高于脂联素RNAi组(P＜0.01).钳夹结束时,脂联素RNAi组葡萄糖清除率(GRd)明显低于利拉鲁肽组(P＜0.01),而肝糖输出率则明显高于利拉鲁肽组(P＜0.01).结论 长期的利拉鲁肽干预上调了脂联素基因表达缺陷ApoE-/-小鼠血浆脂联素水平,并改善了其胰岛素抵抗.     

高血压患者胰岛素抵抗及其与血脂的关系

目的：初步探讨高血压非糖尿病患者胰岛素敏感性及其与血脂水平的关系。方法：收集高血压患者82例,对照组76例,测定空腹胰岛素（FINS）浓度及空腹血糖（FPG）,计算胰岛素敏感性指数（ISI）;测定胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）;测量身高、体重,计算体重指数（BMI）。结果：①高血压组较对照组FINS增高（21．39±14．21 vs 14．48±11．32,P〈0．05）,ISI降低（-4．59±0．5 vs -4．18±0．54,P〈0．05）,TG升高（2．96±0．58 vs 1．30±0．50,P〈0．05）,HDL-C降低（1．30±0．07 vs 1．86±0．12,P〈0．05）。②以ISI为因变量的多元逐步回归分析显示,影响因素为TG、SBP、BMI和HDL-C（r^2=0．64,P〈0．05）。结论：高血压患者更多存在胰岛素抵抗（IR）和血脂异常,氓与TG、SBP、BMI和HDL-C等因素密切相关。     

Relationship between the insulin resistance and circulating predictive biochemical markers in metabolic syndrome among young adults in western Algeria

AimThe metabolic syndrome (MetS) becomes increasingly obvious from an early age. The current study aimed at exploring the relationship between insulin resistance and the main biomarkers of MetS in young adult algerian patients.MethodsGlucose, HbA1C, total cholesterol (TC), hjgh bensity lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulinemia and C-peptide, adipokins (leptin, adiponectin), inflammatory cytokines (IL-6 and TNF-a), us-CRP and GLP-1 were measured by suitable methods. Homeostasis model assessment (HOMA) was used to detect the degree of insulin resistance.ResultsThe MetS patients displayed higher glucose, insulin, HbA1c values and impaired lipid profile as judged by increasing TC, TG, LDL-C levels and lower HDL-C. Furthermore, adipokines, HDL-C and CRP contents were significantly higher whilst TG and LDL-C were much lower in MetS female group as compared to male patients suggesting most pronounced metabolic perturbation in the latter group. The probability of a significant correlation between HOMA and studied variables was often higher in female than male subjects. Such was the case for total cholesterol, HDL-cholesterol, triglycerides, adiponectin, interleukin-6, TNF-α and hs-CRP.ConclusionThe high rate of metabolic syndrome among young obese adults is alarming, this requiring extensive investigations in prone subjects.     

Relative impact of low-density lipoprotein-cholesterol concentration and insulin resistance on carotid wall thickening in nondiabetic, normotensive volunteers

The relative effect of an increase in low-density lipoprotein-cholesterol (LDL-C) concentration, as compared with insulin resistance and its manifestations, on intimal medial thickening (IMT) of the common carotid artery was defined in 72 healthy men and women. Insulin-mediated glucose disposal was quantified by the insulin suppression tests, in which the height of the steady-state plasma glucose (SSPG) concentration during the last 30 minutes of a 180-minute infusion of octreotide, insulin, and glucose provides an estimate of insulin resistance. IMT was determined by high-resolution B-mode ultrasonography. Univariate analyses defined statistically significant correlation coefficients between IMT and LDL-C concentration (r =.25, P <.05), SSPG concentration (r =.32, P <.01), triglycerides (TG) (r =.25, P <.05), and high-density lipoprotein-cholesterol (HDL-C) (r = -.28, P <.05) concentrations (changes associated with insulin resistance) and ratio of waist-to-hip girth (r =.29, P <.05). When forward step-wise linear regression analysis was used, concentrations of SSPG, LDL-C and HDL-C all emerged as independent predictors of IMT (P <.05). Furthermore, the magnitude of their relationship to IMT values was comparable. These results provide evidence that insulin resistance is as significant a predictor of degree of atherogenesis (estimated by IMT) of the common carotid artery as a high LDL-C concentration.     

Serum leptin in formerly small-for-gestational-age children during adolescence: relationship to gender, puberty, body composition, insulin sensitivity, creatinine, and serum uric acid

Serum leptin levels reflect body fat mass (FM), and have been described to be related to serum uric acid levels in adult type 2 diabetic and healthy subjects. We therefore aimed to evaluate the interrelationship between leptin and markers of the metabolic syndrome by studying serum leptin concentration, body mass index (BMI), percent body fat (Fat%), total fat mass (FM), sum of skinfolds (SS), triglycerides (TG), total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), glucose, insulin, calculated insulin resistance (HOMA), creatinine (CR), and uric acid (UA) concentration in 50 former small-for-gestational-age (SGA) children and 21 infants born adequate for gestational age (AGA) at the time of mid-puberty. Our data confirm previous results showing a positive association between leptin and body fatness, and female gender. Twelve children with impaired glucose tolerance (IGT) had higher UA levels than subjects with normal glucose tolerance (NGT) (5.1 +/- 1.1 v 4.2 +/- 1.2 mg/dL, P <.05), and showed the strongest relation between serum leptin and UA (r =.76, P <.001). Multiple regression analyses demonstrated that gender, estimates of total body adiposity (Fat% and SS), birth weight (BW), gestational age (GA), stimulated glucose and insulin, and serum UA are independently associated with serum leptin concentration in former SGA children with dysglycemia (R(2) =.89, P <.001). A long-term effect of intrauterine growth restriction on body fatness, metabolic syndrome, and serum leptin levels is suggested.     

Biomarker models as surrogates for the disposition index in the Insulin Resistance Atherosclerosis Study

Aims Insulin sensitivity and acute insulin response measure key components of Type 2 diabetes aetiology that contribute independently to risk in the Insulin Resistance Atherosclerosis Study. As insulin sensitivity and acute insulin response are not routinely measured in a clinical setting, we evaluated three fasting biomarker models, homeostasis model assessment of insulin sensitivity (HOMA‐%S), β‐cell function (HOMA‐%B) and a Diabetes Risk Score, as potential surrogates for risk associated with insulin sensitivity, acute insulin response and the interaction of these two measures, the disposition index. Methods Models were calculated from baseline plasma biomarker concentrations for 664 participants who underwent a frequently sampled intravenous glucose tolerance test. To assess relationships among biomarker models and test measures, we calculated improvement in risk estimation gained by combining each fasting measure with each frequently sampled intravenous glucose tolerance test measure using logistic regression. Results The strongest correlates of acute insulin response, insulin sensitivity and disposition index were HOMA‐%B (r_s² = 0.23), HOMA‐%S (r_s² = 0.48) and Diabetes Risk Score (r_s² = 0.34), respectively. Individual areas under the curves for prediction of diabetes were 0.549 (HOMA‐%B), 0.694 (HOMA‐%S), 0.700 (insulin sensitivity), 0.714 (acute insulin response), 0.756 (Diabetes Risk Score) and 0.817 (disposition index). Models combining acute insulin response with Diabetes Risk Score (area under the curve 0.798) or HOMA‐%S (area under the curve 0.805) nearly equalled disposition index, outperforming other individual measures (P < 0.05). Insulin sensitivity plus Diabetes Risk Score (area under the curve 0.760) was better than insulin sensitivity (P = 0.03), but not better than Diabetes Risk Score alone. HOMA‐%S plus insulin sensitivity (area under the curve 0.704) was not significantly better than either alone. Conclusions The Diabetes Risk Score and HOMA‐%S were excellent surrogates for insulin sensitivity, capturing the predictive power of insulin sensitivity. Diabetes Risk Score captured some of the additional predictive power of acute insulin response, but the HOMA models did not. No fasting model was as predictive as disposition index, but the Diabetes Risk Score was the best surrogate.     

Adipocyte fatty acid-binding protein is associated with markers of obesity, but is an unlikely link between obesity, insulin resistance, and hyperandrogenism in polycystic ovary syndrome women

OBJECTIVE: Many polycystic ovary syndrome (PCOS) women suffer from adiposity and insulin resistance (IR), which play an important role in the development and maintenance of PCOS. Adipocyte fatty acid-binding protein (A-FABP) is mainly expressed in adipocytes, and circulating A-FABP has been associated with markers of obesity and IR. Thus, as observed with other adipose tissue derived factors, secreted A-FABP might be involved in the pathogenesis of obesity-associated disorders such as PCOS. DESIGN: Plasma A-FABP concentrations were measured in 102 non-diabetic PCOS women, and associations with markers of obesity, IR, inflammation, and hyperandrogenism were investigated by correlation and multiple linear regression analyses. The effect of lifestyle intervention on A-FABP was studied in a second cohort of 17 obese PCOS women. RESULTS: A-FABP correlated with body mass index (BMI; R = 0.694, P < 0.001), dual-energy X-ray-absorptiometry (DEXA) fat mass (R = 0.729, P < 0.001), DEXA lean body mass (R = 0.399, P = 0.001), HOMA %S (R = -0.435, P < 0.001), hsCRP (R = 0.355, P = 0.001), and free testosterone (fT; R = 0.230, P = 0.02). Adjusted for age, smoking, and glucose metabolism the association of A-FABP with HOMA %S was still significant (P < 0.001), whereas the associations with fT (P = 0.09) and hsCRP (P = 0.25) were not. Inclusion of BMI into the model abolished the impact of A-FABP on HOMA %S. In BMI-matched PCOS women (n = 20 pairs), neither HOMA %S (P = 0.3) nor fT (P = 0.6) were different despite different A-FABP levels (P < 0.001), and in 17 obese PCOS women undergoing a lifestyle intervention, changes in IR were not paralleled by changes in A-FABP. CONCLUSIONS: Circulating A-FABP was correlated with markers of obesity, but had no major impact on IR, inflammation, or hyperandrogenemia in PCOS women.     

Effects of morbid obesity on insulin clearance and insulin sensitivity in several aspects of metabolism as assessed by low-dose insulin infusion.

Obesity is associated with impaired insulin action in glucose disposal, but not necessarily in other aspects of intermediary metabolism or insulin clearance. Sixteen morbidly obese and 14 normal-weight subjects (body mass index, 51.2 +/- 11.5 v 22.1 +/- 2.2 kg.m-2; mean +/- SD) were studied with sequential, low-dose, incremental insulin infusion with estimation of glucose turnover. In obese patients, basal plasma insulin was higher (10.5 +/- 3.8 v 2.4 +/- 3.0 mU.L-1, P less than .001) and remained elevated throughout infusion (F = 492, P less than .001), as did C-peptide (F = 22.7, P less than .001). Metabolic clearance rate for insulin (MCRI) at the highest infusion rate was similar (1,048 +/- 425 v 1,018 +/- 357 mL.m-2.min-1, NS). Basal hepatic glucose production in obese subjects was less than in normal-weight subjects (270 +/- 108 v 444 +/- 68 mumol.m-2.min-1, P less than .01), as was the basal metabolic clearance rate for glucose (MCRG, 77 +/- 26 v 108 +/- 31 mL.m-2.min-1, P less than .05). Insulin infusion caused blood glucose to decrease less in the obese patients (1.4 +/- 0.5 v 1.9 +/- 0.5 mmol.L-1, P less than .05); hepatic glucose production was appropriately suppressed in them by hyperinsulinemia, but their insulin-mediated glucose disposal was reduced (1.67 [0.79] v 4.45 [2.13] mL.m-2.min-1/mU.L-1, P less than .01). Concentrations of nonesterified fatty acids (NEFA), glycerol, and ketones were elevated throughout the insulin infusions in obese patients, despite the higher insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Genotype-influenced changes in serum HDL cholesterol after short-term overfeeding in man: association with plasma insulin and triglyceride levels

Six pairs of male monozygotic (MZ) twins were submitted to a 22-day overfeeding period during which they ingested a daily surplus of 1,000 kcal above their individual daily energy needs in the form of a mixed diet. Serum lipids, lipoproteins, and apoprotein A and B concentrations were measured before and after the overfeeding period. Percentage of body fat, fasting plasma glucose, and insulin levels as well as plasma glucose and insulin concentrations after a glucose challenge were also measured before and after overfeeding. Results showed that before overfeeding, MZ twins exhibited a significant intrapair resemblance for total serum cholesterol (CHOL), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), and for the high density lipoprotein-cholesterol/total cholesterol ratio (HDL-C/CHOL) (8.2 less than or equal to F ratios less than or equal to 32.7, P less than .01). The overfeeding experiment induced significant increases only in serum CHOL (P less than .01) and in serum LDL-C (P less than .05). However, although mean group values of serum TG, HDL-C, and HDL-C/CHOL ratio were not significantly modified by overfeeding, there were large interindividual variations in the response of these variables to the experiment. Results suggest that changes in serum TG, HDL-C, and in the HDL-C/CHOL ratio were significantly associated with the genotype of the subjects as a significant intrapair resemblance in the response to overfeeding was observed for these variables (0.69 less than or equal to r less than or equal to .85, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome

OBJECTIVE: The polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance predisposing to diabetes mellitus type 2 and atherosclerosis. Adiponectin is a recently discovered adipocytokine with insulin-sensitizing and putative antiatherosclerotic properties. The aim of the study was to elucidate determinants of circulating adiponectin levels and to investigate the potential role of adiponectin in insulin resistance in PCOS women. PATIENTS AND MEASUREMENTS: Plasma adiponectin and parameters of obesity, insulin resistance and hyperandrogenism were measured In 62 women with PCOS and in 35 healthy female controls. RESULTS: Both in PCOS and controls, adiponectin levels were lower in overweight or obese women than in normal-weight women, without any difference between PCOS and controls after adjustment for body mass index (BMI). In PCOS and in controls there was a significant correlation of adiponectin with BMI (r = -0.516, P < 0.001), fasting insulin (r = -0.404, P < 0.001), homeostasis model sensitivity (HOMA %S) (r = -0.424, P < 0.001) and testosterone (r = -0.279, P < 0.01), but no correlation with androstenedione (r = -0.112, P = 0.325), 17-OH-progesterone (r =-0.031, P = 0.784) or the LH/FSH ratio (r =-0.033, P = 0.753). Multiple linear regression analysis revealed that BMI and HOMA %S but not testosterone were independently associated with adiponectin plasma levels, explaining 16% (BMI) and 13% (HOMA %S) of the variability of adiponectin, respectively. In PCOS patients insulin sensitivity, as indicated by continuous infusion of glucose with model assessment (CIGMA %S) was significantly correlated with adiponectin (r = 0.55; P < 0.001), BMI (r =-0.575; P < 0.001), waist-to-hip ratio (WHR) (r =-0.48; P = 0.001), body fat mass assessed by dual-energy X-ray-absorptiometry (DEXA) [Dexa-fat (total) (r = -0.61; P < 0.001) and Dexa-fat (trunk) (r = -0.59; P < 0.001)] and with testosterone (r = -0.42; P = 0.001). Multiple linear regression analysis demonstrated that markers of obesity such as BMI, total or truncal fat mass, age and adiponectin were independently associated with CIGMA %S, and that circulating adiponectin accounted for about 18% of the degree of insulin resistance in PCOS. By contrast, testosterone was not a significant factor, suggesting that PCOS per se did not affect insulin sensitivity independent from obesity, age and adiponectin. Metformin treatment for 6 months in insulin-resistant PCOS women (n = 9) had no effect on plasma adiponectin (P = 0.59) despite significant loss of weight and fat mass and improvement in hyperandrogenaemia. CONCLUSIONS: PCOS per se is not associated with decreased levels of plasma adiponectin. However, circulating adiponectin is independently associated with the degree of insulin resistance in PCOS women and may contribute to the development and/or maintenance of insulin resistance independent from adiposity.     

Insulin resistance and impaired glucose tolerance in obese children and adolescents referred to a tertiary-care center in Israel

OBJECTIVE: To establish the prevalence of insulin resistance and impaired glucose tolerance (IGT) and their determinants in a cohort of obese children and adolescents. METHODS: A retrospective design was used. The study group included 234 patients with a body mass index (BMI) greater than the 95th percentile for age and gender and 22 patients with a BMI between the 85th and 95th percentile for age and gender referred for evaluation to a major tertiary-care center in Israel. Ages ranged from 5 to 22 y. Estimates of insulin resistance (homeostatic model assessment (HOMA-IR)); insulin sensitivity (ratio of fasting glucose (GF) to fasting insulin (IF) (GF/IF), the quantitative insulin sensitivity check index (QUICKI)), and pancreatic beta-cell function (HOMA-derived beta-cell function (HOMA %B)) were derived from fasting measurements. An oral glucose tolerance test (OGTT) was performed in 192 patients to determine the presence of IGT. RESULTS: Insulin resistance was detected in 81.2% of the patients, IGT in 13.5%, and silent diabetes in one adolescent girl. Only two patients with IGT also had impaired fasting glucose (IFG). The prevalence of IGT was higher in adolescents than prepubertal children (14.7 vs 8.6%). GF/IF and QUICKI decreased significantly during puberty (P<0.005), whereas HOMA-IR and HOMA %B did not. Insulin resistance and insulin sensitivity indexes were not associated with ethnicity, presence of acanthosis nigricans or family history of type 2 diabetes. Patients with obesity complications had lower insulin sensitivity indexes than those without (P=0.05). Compared with subjects with normal glucose tolerance (NGT), patients with IGT had significantly higher fasting blood glucose (85.9+/-6.5 vs 89.2+/-10.6 mg/dl, P<0.05), higher 2-h post-OGGT insulin levels (101.2+/-74.0 vs 207.6+/-129.7 microU/ml, P<0.001), a lower QUICKI (0.323+/-0.031 vs 0.309+/-0.022, P<0.05), and higher fasting triglyceride levels (117.4+/-53.1 vs 156.9+/-68.9, P=0.002). However, several of the fasting indexes except QUICKI failed to predict IGT. There was no difference between the group with IGT and the group with NGT in fasting insulin, HOMA-IR, HOMA %B or the male-to-female ratio, age, BMI-SDS, presence of acanthosis nigricans, ethnicity, and family history of type 2 diabetes.CONCLUSIONS:Insulin resistance is highly prevalent in obese children and adolescents. The onset of IGT is associated with the development of severe hyperinsulinemia as there are no predictive cutpoint values of insulin resistance or insulin sensitivity indexes for IGT, and neither fasting blood glucose nor insulin levels nor HOMA-IR or HOMA %B are effective screening tools; an OGTT is required in all subjects at high risk. Longitudinal studies are needed to identify the metabolic precursors and the natural history of the development of type 2 diabetes in these patients.     

低碳水化合物高营养密度膳食对肥胖儿童青少年的减重效果及糖脂代谢的影响

目的探讨低碳水化合物高营养密度膳食对肥胖儿童青少年的减重效果及糖脂代谢的影响。 方法选取2020年6月至2021年6月惠州市中心人民医院肥胖门诊及营养门诊的肥胖儿童青少年（7~18岁）37例作为研究组,选取同期22例肥胖儿童青少年作为对照组,对照组采用平衡膳食及生活方式、运动宣教干预,研究组在生活方式、运动宣教干预的基础上,采用低碳水化合物高营养密度膳食干预,共干预8周,比较两组干预前后BMI、腰臀比、身体成分分析数据以及代谢指标水平。 结果两组患者干预前的BMI、腰围、臀围、腰臀比、体脂率、内脏脂肪面积对比差异均无统计学意义（P>0.05）,在干预8周后,研究组的BMI、腰围、臀围、腰臀比、体脂率和内脏脂肪面积显著低于对照组,差异具有统计学意义（P<0.05）;干预前两组的空腹血糖（FPG）、餐后2 h血糖（2hPG）、空腹胰岛素（FINS）、餐后2 h胰岛素（2hINS）、血尿酸（UA）、血清胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）比较差异均无统计学意义（P>0.05）,干预8周后研究组的FPG、2hPG、FINS、2hINS、UA、TC、TG、LDL-C水平均显著低于干预前,且显著低于对照组,差异具有统计学意义（P<0.05）。 结论低碳水化合物高营养密度膳食短期内可以有效使肥胖儿童青少年减重,减少体脂率和内脏脂肪面积,改善其糖脂代谢。     

Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration

BACKGROUND: Hyperinsulinemia/insulin resistance and elevated plasma free fatty acids (FFA) levels are involved in the hypertension and cardiac sympathetic overactivity. Metformin improves insulin action and lower plasma FFA concentrations. We investigate the possible effect of metformin on arterial blood pressure (BP) and cardiac sympathetic nervous system. METHODS: One hundred twenty overweight type 2 diabetic patients were treated by placebo (n = 60) + diet or metformin (850 mg twice daily) (n = 60) + diet for 4 months, to evaluate the effect of metformin treatment on the cardiac autonomic nervous system. Insulin resistance was measured by the Homeostasis Model Assessment (HOMA) index. Heart rate variability (HRV) assessed cardiac sympathovagal balance. RESULTS: Metformin treatment, but not placebo treatment, was associated with a decrease in fasting plasma glucose (P <.05), insulin (P <.05), triglyceride (P <.05), and FFA (P <.03) concentrations and HOMA index (P <.03). Metformin treatment was also associated with a significant improvement in cardiac sympathovagal balance but not in mean arterial BP. Furthermore, in a multivariate analysis, delta change in sympathovagal balance index (LF/HF ratio) were associated with delta change in plasma FFA concentrations and HOMA index independently of gender and delta change in plasma triglyceride and HbA1c concentrations. CONCLUSIONS: Our study demonstrated that metformin treatment might be useful for improving cardiac sympathovagal balance in obese type 2 diabetic patients.     

Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids

Aim: Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short‐term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). Methods: Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n = 7) or FHD (n = 6). By using specifically designed formulae, we calculated four insulin‐sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)‐b, ISI (gly)‐a, ISI (ffa)‐b and ISI (ffa)‐a. Results: In patients with diabetes or FHD, MET improved ISI (gly)‐b (0.79 ± 0.06 vs. 0.59 ± 0.07, p < 0.001) and ISI (gly)‐a (0.69 ± 0.09 vs. 0.51 ± 0.07, p < 0.05), whereas only minor changes occurred for ISI (ffa)‐b and ISI (ffa)‐a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)‐a (0.47 ± 0.07 vs. 0.64 ± 0.10, p < 0.01) and ISI (ffa)‐a (0.43 ± 0.07 vs. 0.55 ± 0.08, p < 0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p < 0.01), however, was observed for the ‘decremental’ area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. Conclusions: Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and ‘prediabetic’ obese patients, whereas worsened it in the obese subjects without FHD. Therefore, the effects of MET would not be secondary to changes of FFA but rather to a primary action of MET on glucose metabolism. Thus, utilization of MET to treat the insulin resistance in obesity is indicated only in the presence of alterations of glucose metabolism or FHD.     

Obstructive sleep-disordered breathing and fasting insulin levels in nonobese children

A positive correlation of severity of sleep-disordered breathing with morning fasting insulin levels, which is independent of obesity, was reported in adults and obese children. We hypothesized that both severity of sleep-disordered breathing and relative body mass index predict fasting insulin and homeostasis model assessment (HOMA) index values in nonobese children with habitual snoring. One hundred and ten subjects with habitual snoring (median age, 6 years; range, 2-13 years) underwent polysomnography and measurement of morning fasting insulin and glucose levels. The HOMA index was calculated. Thirty children had an apnea-hypopnea index (AHI) >/= 5 episodes/hr (median, 7.8 episodes/hr; range, 5-42.3 episodes/hr), and 80 subjects had an AHI < 5 episodes/hr (median, 1.9 episodes/hr; range, 0.2-4.9 episodes/hr). Insulin and HOMA index values were similar in children with AHI >/= 5 episodes/hr (median insulin, 4.9 mU/l; range, 1.66-19.9 mU/l; and median HOMA, 1; range, 0.36-4.95) and in subjects with AHI < 5 episodes/hr (median insulin, 5.8 mU/l; range, 0.74-41.1 mU/l; and median HOMA, 1.3; range, 0.13-9.72) (P > 0.05). No significant correlations were identified between insulin or HOMA index values and any polysomnography indices (P > 0.05). When multiple linear regression was carried out, relative body mass index was a significant predictor of log-transformed insulin levels or HOMA index values, but AHI and percentage of sleep time with saturation <95% were not. In conclusion, contrary to findings in adults and in obese children, severity of sleep-disordered breathing is not a significant predictor of fasting insulin or HOMA index values in nonobese children with habitual snoring.     

高脂喂养对ApoE基因敲除小鼠胆固醇代谢相关基因表达的影响

建立高脂诱导载脂蛋白E基因敲除(ApoE-/-)小鼠胰岛素抵抗模型,探讨其对胆固醇代谢相关基因表达的影响.结果 显示高脂喂养组ApoE-/-小鼠空腹血糖、游离脂防酸、总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和空腹血浆胰岛素水平明显高于对照组(均P＜0.01);肝组织中INSIG2和SCAP mRNA明显升高(P＜0.05或P＜0.01),肝INSIG2蛋白水平也明显增高(P＜0.05);而SREBP1 mRNA表达明显降低(P＜0.05).这些改变可能在该小鼠模型胆固醇代谢紊乱和胰岛素抵抗的发生中具有一定的作用.

Abstract：

To investigate the effect on gene expression related cholesterol metabolism in ApoE-/- mice with high-fat-induced insulin resistance(IR). In high-fat fed mice, FBG, FFA, TC, TG, LDL-C, HDL-C, and fasting plasma insulin were significantly higher than those of controls(P＜0.01). The INSIG2 and SCAP mRNA expressions in liver were significantly increased in high-fat fed mice compared with controls(P＜0. 05 or P＜0.01), and INSIG2 protein levels also increased(P＜0. 05). But SREBP1 mRNA expression in liver of high-fat fed mice was significantly reduced(P＜0. 05). These changes might contribute to IR and disorder of cholesterol metabolism in high-fat fed ApoE-/- mice.     

RNAi介导的脂联素基因沉默对ApoE基因敲除小鼠糖脂代谢的影响

探讨脂联素基因表达缺陷对ApoE基因敲除(ApoE~(-/-))小鼠糖脂代谢的影响.注射短发卡RNA(shRNA)腺病毒后高脂喂养的ApoE~(-/-)小鼠(ADI组)血浆脂联素水平明显低于普食喂养(NF)、单纯高脂喂养(HF)和空载腺病毒高脂对照组(GF,均P<0.01).3组高脂喂养的APOE~(-/-)小鼠体重、空腹血糖、血浆游离脂肪酸、总胆固醇、甘油三酯、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和血浆胰岛素水平明显高于NF组(均P<0.01),而ADI组与HF和GF组相比,游离脂肪酸、总胆同醇、甘油三酯、LDL-C、HDL-C和血浆胰岛素水平增高更为明显(P<0.01或P<0.05),提示长期高脂饲养和脂联素基因表达缺陷使ApoE~(-/-)小鼠具备较为典型的糖脂代谢紊乱和胰岛素抵抗的病理生理表现.