二甲双胍对假性黑棘皮病胰岛素抵抗及高胰岛素血症的作用

假性黑棘皮病 (ａｃａｎｔｈｏｓｉｓｎｉｇｒｉｃａｎｓ,ＡＮ)是一种胰岛素抵抗、高胰岛素血症、高雄激素血症的皮肤特征性改变 ,在不同的胰岛素抵抗综合征中常常伴有假性ＡＮ。胰岛素抵抗和代偿性高胰岛素血症已被证明对糖尿病、肥胖、高血压、高脂血症等疾病的发生起着重要的促进作用。及早发现和识别高胰岛素血症并给予早期干预治疗是目前临床研究的重点。二甲双胍除降低血糖外 ,可改善机体对胰岛素的敏感性 ,增加细胞的胰岛素受体数目 ,从而改善高胰岛素血症。本研究旨在观察二甲双胍对假性ＡＮ中胰岛素抵抗及高胰岛素血症、高雄激素血…     

二甲双胍的近期应用

二甲双胍主要用于单纯饮食控制不满意的2型糖尿病患者，尤其是肥胖和伴高胰岛素血症者。除此，近期对二甲双胍在临床上的应用还有一些新的报道。     

国外重要心血管杂志论文文摘

肥胖性2型糖尿病人血压与心脏自主神经系统:二甲双胍的效果AmJofHypertension 2 0 0 4 ,17:2 2 3 2 2 7 　　高胰岛素血症/胰岛素抵抗与血浆游离脂肪酸增高与高血压及心脏交感神经过度兴奋有关。二甲双胍改善胰岛素作用,降低游离脂肪酸。我们研究二甲双胍能否降压与改善心脏自主神经系统。12 0名肥胖性2型糖尿病人用安慰剂(n =6 0 ) ,加饮食或二甲双胍(85 0ngBid) (n =6 0 )加饮食治疗共4月,胰岛素抵抗用HomeostasisModelAssessment(HOMA)测定,用心率变异性判定心脏交感一迷走平衡。结果:二甲双胍治疗降低空腹血糖(P <0 0 5 ) ,胰岛素…     

二甲双胍治疗伴高胰岛素血症超重青少年临床研究

32名年龄在12～18周岁的肥胖或超重青少年(男18名,女14名),经1个月饮食和运动治疗后,体重无变化后进行葡萄糖耐量试验和胰岛素检查,并检测身高、体重、血压和心率,计算体重指数(BMI)和胰岛素敏感指数(1/空腹血糖×空腹胰岛素).随机分为两组,治疗组给予二甲双胍(格华止)1000mg/d,对照组给予外观相同的赋形剂,疗程3个月.结果治疗组体重略有减轻,空腹和餐后胰岛素水平明显降低,临床表现明显改善.结论二甲双胍治疗伴高胰岛素血症肥胖或超重青少年,疗效可靠,安全性好.关于长期疗效和安全性需进一步扩大样本量和延长时间进行研究.     

二甲双胍治疗肥胖伴高胰岛素血症非糖尿病儿童疗效

目的对二甲双胍治疗患有高胰岛素血症的非糖尿病肥胖症儿童的安全性和有效性进行探讨。方法选取2012年7月—2014年7月在该院进行治疗的24例肥胖症伴高胰岛素血症患儿,随机分为对照组和治疗组,对照组12例患儿的治疗方式为饮食控制和锻炼,治疗组12例患儿的治疗方式为在饮食控制和锻炼的基础上服用二甲双胍。观察两组患者治疗前后的体质量指数(BMI)和胰岛素抵抗指数(HOMA-IR),手术后观察两组患者的不良反应情况。结果治疗组患者治疗前后的BMI和HOMA-IR有明显的下降,对照组患者治疗前后BMI有明显下降,但HOMA-IR并无明显变化。不良反应方面,治疗组患者治疗2周内有3例患者发生腹部不适及腹泻,治疗1个月时,1例患儿出现发热伴腹泻症状,治疗3~6个月后,对患者进行随访,并无异常反应。结论二甲双胍在治疗患有高胰岛素血症的肥胖症患儿方面,有着显著的疗效,而且二甲双胍的安全性也较高。     

对双胍类降糖药──二甲双胍的新评价

对双胍类降糖药──二甲双胍的新评价钱荣立双胍类口服降糖药──二甲双胍（ｒｎｅｔｆｏｒｍｉｎＨＣＥ）早在１９５７年就开始用于临床。随着对双胍类降糖药作用机制的深入研究，以及近年来关于胰岛素抵抗与高胰岛素血症在Ⅱ型糖尿病（ＮＩＤＤＭ）发病北京医科大学第一...     

关注多囊卵巢综合征与胰岛素抵抗

多囊卵巢综合征（PCOS）患者无论是否肥胖，均存在胰岛素抵抗（IR），可表现为高胰岛素血症和糖代谢异常。PCOS患者不仅存在IR，而且有胰岛β细胞功能障碍。PCOS患者IR的发生与胰岛素受体后信号通道缺陷有关。治疗措施包括改善不良的生活方式、减轻体重、二甲双胍等。     

二甲双胍治疗糖尿病的疗效观察

目的 观察二甲双胍治疗糖尿病的疗效.方法 选择120例2型糖尿病患者（观察组）行瑞格列奈＋二甲双胍药物治疗,另120例2型糖尿病患者（对照组）行瑞格列奈药物治疗,观察两组疗效.结果 治疗后两组患者的FBS、PBS、HbA1c、TG以及TC指标均低于治疗前;且观察组各指标明显低于对照组.结论 二甲双胍能够改善肥胖糖尿病患者空腹及餐后高血糖及高三酰甘油血症而不致使体质量增加,还能够调节患者的血脂代谢紊乱、改善舒张压、改善胰岛素抵抗及高胰岛素血症,预防糖尿病的发生,达到很好的治疗效果.     

多种治疗方式干预在肥胖合并高胰岛素血症人群中的应用效果

目的探究多种治疗方式干预在肥胖合并高胰岛素血症人群中的应用效果。方法 86例肥胖合并高胰岛素症患者随机分组,各43例。对照组予以一般治疗、饮食及运动干预;实验组在对照组基础上予以(二甲双胍、奥利司他、芬特明)+手术治疗(胃旁路手术)。对比两组治疗效果、治疗后3、6个月随访体质量(BMI)、空腹血糖(FBG)、餐后2 h血糖(2 hPG)、空腹胰岛素(FINS)、胰岛素抵抗(IR)、胰岛素敏感性(IS)。结果实验组有效率高于对照组(P0.05);治疗后3、6个月实验组BMI、2 hPG、FBG低于对照组(P0.05);FINS、IR、IS均低于对照组(P0.05)。结论多种治疗方式干预用于肥胖合并高胰岛素血症人群疗效显著,可控制血糖,降低胰岛素水平。     

孕期服用二甲双胍对血糖正常合并高胰岛素血症的多囊卵巢综合征妇女妊娠结局的影响

目的:探讨孕期服用二甲双胍对血糖正常但合并高胰岛素血症的多囊卵巢综合征(PCOS)妇女妊娠结局及妊娠期并发症的影响。方法:选取重庆医科大学附属第二医院2017年1月至2019年12月收治的130例血糖正常但合并高胰岛素血症的妊娠期PCOS患者,分为2组,治疗组孕期进行二甲双胍治疗,对照组进行生活方式干预,比较2组间妊娠...     

Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia

This study examined the prevalence of both basal and glucose-stimulated hyperinsulinemia and acanthosis nigricans (AN) as well as the relationship between insulin and androgen levels in hyperandrogenic women. Sixty-two women who had an elevation of 1 or more plasma androgen levels were studied. The results in these women, grouped for analysis on the basis of obesity and ovulatory status, were compared to those in 36 control women of similar ages and weights. The anovulatory hyperandrogenic women had the clinical and biochemical features of the polycystic ovary syndrome (PCO). Oral glucose tolerance tests were performed with measurement of glucose, insulin, sex hormone-binding globulin (SHBG), and total and non-SHBG-bound sex steroid levels. AN was present in 29% of the hyperandrogenic women, the majority of them obese. Fifty percent of obese PCO women had AN, but they did not otherwise differ from PCO women lacking this dermatological change. Only women with PCO had significant hyperinsulinemia independent of obesity, and obese PCO women with AN had the highest serum insulin levels. Plasma glucose values during the oral glucose tolerance test were significantly increased in obese PCO women independent of the presence of AN, and 20% of these women had frank impairment of glucose tolerance. Ovulatory hyperandrogenic women had normal insulin levels and glucose tolerance. Obese and nonobese women had different relationships between sex steroid and insulin levels; obese women had significant correlations between insulin and non-SHBG testosterone levels (r = 0.30; P less than 0.05), whereas nonobese women had significant correlations between insulin and FSH (r = 0.40; P less than 0.01), dehydroepiandrosterone sulfate (r = 0.33; P less than 0.05), and SHBG (r = 0.37; P less than 0.05) levels, suggesting that the mechanisms underlying the association between sex steroid and insulin levels are complex. These findings suggest that 1) only women with PCO have hyperinsulinemia independent of obesity; hyperinsulinemia is not a feature of hyperandrogenic states in general; 2) AN is a common finding in obese hyperandrogenic women, particularly those with PCO; 3) only obese PCO women are at risk for impairment of glucose tolerance, independent of the presence of AN, suggesting that the negative impact of PCO and obesity on insulin action is additive; and 4) PCO women with AN can be considered as a subgroup of PCO and do not appear to have a distinct endocrine disorder.     

肥胖儿童黑棘皮病严重程度与胰岛素抵抗的相关性研究

目的 探究肥胖儿童的各项指标尤其是胰岛素抵抗随着黑棘皮病(AN)程度加重的变化情况,分析黑棘皮病严重程度预测胰岛素抵抗的能力.方法 回顾性分析2018年3月到2020年1月在天津医科大学总医院儿科就诊的88例肥胖儿童的临床资料,收集一般资料:身高、体重、腰围、收缩压及舒张压,检测儿童的葡萄糖、胰岛素、谷丙转氨酶、谷草转...     

Reduction of hyperinsulinemia and insulin resistance by opiate receptor blockade in the polycystic ovary syndrome with acanthosis nigricans

We previously reported that circulating beta-endorphin levels are increased in obese hirsute women and that plasma immunoreactive insulin (IRI) levels are increased in proportion to the degree of hyperandrogenism in women with the polycystic ovary (PCO) syndrome. We, therefore, tested the hypothesis that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in this syndrome. In the first study, acute naloxone administration significantly reduced the plasma IRI response and IRI/glucose ratio in three euglycemic obese women with PCO and acanthosis nigricans (AN) and marked insulin resistance, but did not alter the glucose response. Naloxone had no effect on these parameters in the normal weight control subjects. In the second study, nalmefene, a new, orally active opiate antagonist, reduced IRI and the IRI/glucose ratio in four women with PCO-AN and marked hyperinsulinemia in a randomized, double blind, crossover protocol. We conclude that endogenous opiates are at least partially responsible for the hyperinsulinemia and insulin resistance in PCO-AN.     

Adipose tissue and liver lipid metabolism in obese children: role of the body mass index and the presence of acanthosis nigricans.

AIMS: The aims of our study were to determine if insulin resistance is associated with increased plasma levels of non-esterified fatty acids (NEFA), glycerol, 3-hydroxybutyrate and triglycerides in obese children. We also studied whether the presence of acanthosis nigricans (AN) led to further alterations in the above parameters. METHODS: A total of 101 children were studied on their first visit to the paediatric endocrine clinic. Seventy-four were obese, 30 of them with AN. The remaining 27 were non-obese healthy children (control group). NEFAs, glycerol, triglycerides, 3-hydroxybutyrate, insulin, leptin, adiponectin and glucose were determined in blood samples obtained after overnight fasting. The insulin resistance index (IRI) was calculated following the homeostasis model assessment (HOMA). Data from the three groups were compared using appropriate statistical tests. RESULTS: No differences in age, sex ratio and pubertal stage were observed among the three groups. The group of children with the highest body mass index (BMI) showed higher plasma levels of insulin and leptin, higher IRI and lower plasma levels of adiponectin. As insulin and IRI increased, NEFA and 3-hydroxybutyrate decreased and triglycerides increased. When obese children were categorized by BMI, the presence of AN further exacerbated these differences. CONCLUSIONS: In obese children, insulin resistance is associated with plasma lipid alterations suggestive of both decreased adipose tissue lipolysis and hepatic beta-oxidation and increased hepatic synthesis of triglycerides. Such a metabolic condition may facilitate fat storage and hinder weight loss.     

Insulin resistance and acanthosis nigricans: evidence for a postbinding defect in vivo

Acanthosis nigricans (AN) with insulin resistance has been traditionally attributed to insulin receptor abnormalities. To further clarify the postbinding defects of in vivo insulin action in this state, we applied the euglycemic insulin clamp technique, combined with the glucose trace infusion method, to 26 subjects: 12 AN patients (eight normoglycemic and four hyperglycemic), eight obese, and eight lean control subjects. The normoglycemic AN group exhibited fasting hyperinsulinemia (666% of control), 160% elevated hepatic glucose production (HGP), 425% increased posthepatic insulin delivery rate, and only slightly reduced (19%) insulin clearance rates, compared with controls. Except for the latter, all these abnormalities were statistically significant (P less than .05), and could not be accounted for by body overweight. AN patients with diabetes mellitus (AN + DM) exhibited a further decreased insulin responsiveness (30%) and clearance (38%), together with a major increase in HGP (320%). All AN patients showed a significant right-shift in the insulin dose-response curve, indicating a decrease in insulin sensitivity. In conclusion, AN is characterized by increased basal rates of HGP, and peripheral insulin resistance, which can be partially attributed to postbinding defects. In AN + DM, a worsening of these abnormalities may be responsible for unmasking the existence of diabetes.     

Lower birth weight and visceral fat accumulation are related to hyperinsulinemia and insulin resistance in obese Japanese children.

This study aimed to reveal the relation of birth weight (or the birth weight standard deviation score [BWSDS]) and visceral fat accumulation to hyperinsulinemia and insulin resistance. We examined obese Japanese children (650 boys and 317 girls) with a mean age of 10.3 years (range, 6-15 years). The mean percentage of overweight to the standard body weight of Japanese children was 52.1% in boys and 51.4% in girls. Abdominal fat thickness (maximum preperitoneal fat thickness; Pmax) was measured using ultrasonography. The fasting serum insulin and plasma glucose levels were measured, and the homeostasis model assessment-insulin resistance (HOMA-R) and quantitative insulin sensitivity check index (QUICKI) were calculated. We divided the subjects into four groups according to their birth weight or BWSDS, and compared anthropometric measurements, Pmax, blood pressure, serum insulin levels, HOMA-R and QUICKI among the quartiles. The relationships of both birth weight (or BWSDS) and Pmax to serum insulin levels (or HOMA-R, QUICKI) were examined with multiple regression analyses. The fasting serum insulin level and HOMA-R were highest in the quartile with the lowest birth weight or BWSDS. The birth weight and BWSDS were inversely related to the serum insulin levels and HOMA-R, positively related to QUICKI, and independent of Pmax. Our findings suggest that both lower birth weight and visceral fat accumulation may be independently related to hyperinsulinemia and insulin resistance in obese Japanese children.     

Added impact of obesity and insulin resistance in nocturnal blood pressure elevation in children and adolescents

The aim of the present study was to analyze the relationship between insulin resistance and the ambulatory blood pressure components in obese children and adolescents. Eighty-seven overweight and obese white children and adolescents of both sexes, of European origin from 6 to 18 years of age (mean age: 10.9+/-2.7 years), were selected. Obesity was defined on the basis of a threshold body mass index z score >2 (Cole's least mean square method) and overweight with a body mass index from the 85th to 97th percentile. A validated oscillometric method was used to measure ambulatory BP (Spacelabs 90207) during 24 hours. Fasting glucose and insulin were measured, and the homeostasis model assessment index was calculated. Subjects were grouped into tertiles of homeostasis model assessment index. No significant differences in terms of age, sex, and body mass index z score distribution were observed among groups. When adjusted by age, sex, and height, nocturnal systolic blood pressure and heart rate were significantly higher in subjects in the highest homeostasis model assessment index tertile (>4.7) as compared with those of the other groups, whereas no differences were observed for awake systolic blood pressure or heart rate. Whereas body mass index z score was more closely related with blood pressure and heart rate values, waist circumference was strongly related with insulin resistance. Moreover, both waist circumference and insulin resistance were mainly associated with higher nocturnal but not with awake blood pressure. The early increment of nocturnal blood pressure and heart rate associated with hyperinsulinemia may be a harbinger of hypertension-related insulin resistance and may contribute to heightened cardiovascular risk associated with this condition.     

Hepatic insulin clearance increases after weight loss in obese children and adolescents.

BACKGROUND: Obesity is a rapidly increasing health problem among US youth. Hyperinsulinemia is associated with obesity and has been found to be a contributory factor for the development of cardiovascular disease in the obese. It has been suggested that hyperinsulinemia of obesity is a result of increased insulin secretion caused by insulin resistance. However, it has been shown in adults that decreased hepatic insulin clearance (HIC) is the primary cause of hyperinsulinemia in this population. METHODS: We studied 15 obese children and adolescents (11 F, 4 M; 8.6 to 18.1 years) before and 10 weeks after their enrollment in a multidisciplinary weight reduction program, which included a protein-sparing modified fast, a moderate intensity progressive exercise program, and a behavior-modification intervention. RESULTS: All patients lost weight (P < 0.05). Measurements of immunoreactive insulin (IRI) and C-peptide reactivity (CPR) were performed before the program and at 10 weeks. IRI levels dropped significantly, whereas CPR levels did not change. CPR/IRI molar ratios, considered an indirect estimation of HIC, rose significantly after weight loss. CONCLUSIONS: Our data suggest that hyperinsulinemia seen in obese children and adolescents is caused by decreased HIC. The cause for this decrease remains unknown, but it is reversible upon weight loss.     

Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children

OBJECTIVE: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6-9 years) of both sexes and its possible influence on the androgenic status. DESIGN: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90(th) percentile and a control group of age- and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17beta-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. RESULTS: The obese group presented significantly elevated levels of insulin (P=0.001) and insulin/glucose ratio (P=0.0012) compared with the control group. SHBG (P=0.0001) and testosterone (P=0.0169) levels were significantly lower than those in the non-obese group. We did not find any difference in the free androgen index (FAI). Fasting insulin (r=-0.4512; P<0.001), BMI (r=-0.3185; P<0.05) and testosterone (r=-0.3705; P<0.01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P=0.0171). CONCLUSIONS: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.     

Insulin Resistance Rather than Hyperinsulinemia More Closely Associated with Essential Hypertension

In order to clarify which of the two, insulin resistance or hyperinsulinemia, are more contributable to non obese and non diabetic hypertension, insulin sensitivity test was performed. By multiple regression analysis, mean, systolic, and diastolic blood pressure were inversely correlated with glucose clearance. During insulin sensitivity test, plasma catecholamines levels and FENa were not changed by insulin infusion.

In the present study, it is demonstrated that insulin has no hypertensive effect under the mild hyperinsulinemia (45–55μU/ml). We conclude that insulin resistance rather than hyperinsulinemia may be more closely associated with non obese and non diabetic hypertension.