摘要
目的探讨酮症倾向糖尿病(KPD)患者的临床特征、胰岛素敏感性和p细胞功能。方法纳入2004年1月至2009年12月在四川大学华西医院内分泌科以自发性酮症起病的初诊糖尿病(KPD)患者31例.根据体重指数分为肥胖组(OB—KPD,n=22)和体重正常组(Lean.KPD,X=9),并选择年龄、性别匹配的肥胖的无酮症倾向初诊糖尿病(OB—DM,X=10)作为对照。检测患者人院时的血糖、HbA、血脂、游离脂肪酸和B-羟丁酸水平,并检测自身抗体包括胰岛细胞抗体(ICA)、胰岛素抗体(IAA)和谷胺酸脱羧酶抗体(GAD—Ab)等指标。所有受试者接受标准餐/胰岛素c肽释放试验、静脉葡萄糖耐量试验(IVGlrr)、正常血糖一高胰岛素钳夹试验(EHCT)以及高血糖钳夹试验(HCT),以EHCT稳态期平均葡萄糖清除率(GDR)反映胰岛素敏感性,以IVGTT胰岛素曲线下面积AUCins。。。评估早相胰岛素分泌反应(AIR),以HCT稳态期平均胰岛素水平(I)和稳态期平均葡萄糖输注速率(GIR)评价胰岛岱细胞最大分泌功能和胰岛素在体内的生物学活性。结果KPD患者起病时均存在严重的高血糖和高游离脂肪酸血症。正常血糖一高胰岛素钳夹试验结果显示,OB—KPD组GDR值为(4.91±1.82)mg·kg一·min~,与Lean—KPD组GDR值『(6.26±1.89)mg·kg·rain。]接近,KPD两组问的平均GDR值差别无统计学意义,但均显著低于OB—DM组患者GDR水平[(6.78±1.69)mg·kg~·min~,P〈0.05],提示KPD患者胰岛素的介导葡萄利用率显著下降,存在明显的胰岛素抵抗。IvG’丌和HCT结果显示:KPD患者的胰岛素早相分泌和最大分泌能力均严重受损,OB—KPD组患者胰岛素分泌的曲线下面AUCins。。.。[(183.86±31.1)mlU/L]和GIR值[(2.654-1.53)mg·kg~·min-1]略高于Lean—KPD组[AUCinsf)_l()n。.(92.1±29.8)mlU/L,GIR(2.55±1.49)mg·kg·min,P〈0.05],但显著低于OB—DM组[AUCins0min(697.064-231.9)mlU/L,GIR(6.534-2.21)mg·kg~·min,P〈0.01]。结论KPD患者起病急性期存在严重的糖脂代谢紊乱和胰岛素抵抗,并存在不同程度的B细胞功能受损。肥胖KPD患者外周胰岛素抵抗更严重,超过体重指数与之接近的OB—DM组,但Lean—KPD患者p细胞功能受损程度更为突出。KPD患者的严重外周胰岛素抵抗和p细胞衰竭与高血糖和高游离脂肪酸血症有关。
Objective To investigate the clinical characteristics, peripheral insulin sensitivity, and 13-cell function in patients with ketosis-prone diabetes( KPD): Methods Thirty-one patients with newly diagnosed ketosis- prone diabetes were admitted to West China Hospital from January 2004 to December 2009. They were divided into 2 groups according to their body mass index (BMI) : OB-KPD ( BMI 〉i 25 kg/m2, n = 22 ) and Lean-KPD ( BMI 〈 23 kg/m~ , n = 9). lO patients with newly-onset type 2 diabetes free from ketosis ( OB-DM : BMI i〉 25 kg/m2 , n = 10) were enlisted as control. Detailed assessments of medical history and symptoms of hyperglycemia were performed. The islet cell antibody ( ICA ), insulin autoantibody ( IAA ), anti-glutamic acid decarboxylase antibody ( GAD-Ab ), fasting plasma glucose, serum insulin, C-peptide and free fat acids concentrations were measured. All of the subjects underwent oral and intravenous glucose tolerance tests, euglycemic-hyperinsulinemia and hyperglycemia clamp test, to evaluate the insulin secretion and insulin sensitivity respectively. Insulin sensitivity was determined by glucose disposal rate ( GDR ) of steady state during euglycemic clamp and acute insulin secretion was calculated by insulin area under curve( AUCins 0-10 rain ) during IVGTI'. Maximal insulin secretion was determined by glucose infusion rate (GIR) and serum insulin concentration of steady state during hyperglycemic clamp test. Results Age, sex, duration of diabetes were matched among groups. A family history of diabetes was strongly associated with those patients with obesity, compared with lean ketosis prone diabetes( 16/22 vs 1/9). GDR was (4.91 + 1.82) mg kg min tinsubjects with OB-KPD, being lower than that in Lean-KPD patients[ (6.26 + 1.89) mg kg-1 rain-1 and OB-DM group[ (6.78 + 1.69) mg kg-1 min-1 , P〈0. O1 . Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients. Area under the insulin curve [ AUCins0_r0mn( 183.86 + 31.1 ) mIU/L] and GIRl (2.65 -+ 1.53 ) mg ~ kg-1 rain-1 ] in OB-KPD patients were lower than those in OB-DM group [ (697.06 + 231.9 ) mlU/L, (6.53 s: 2.21 ) mg kg-1 min , P〈0. Ol I, but slightly higher than the Lean-KPD group [ AUCins0_~o,,,~,, ( 92.1 + 29.8) mIU/L, GIR (2.55 -+ 1.49 )mg ~ kg-] ~ rain ~, P〈O. 05 ]. Glucose disposal rate (GDR) was strongly associated with casual plasma glucose( r= -0. 502, P〈O. O1 ) , HbA^c( r = -0. 553, P〈0. O1 ) and FFA concentrations (r=-0. 504, P〈0.01 ) on admission. Conclusions Insulin resistance and [3-cell dysfunction coexist in all KPD patients. OB-KPD patients exhibit more severe insulin resistance, wtfile Lean-KPD patients have lower insulin secretion. KPD patients had severe hyperglycemia, hypertriglyeeridemia, and high plasma FFA levels on admission, suggesting that hyperglycemia and elevated FFA levels could result in serious insulin resistance, β-cell dysfunction, and diabetic ketosis in oatients with KPD.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2013年第12期1026-1030,共5页
Chinese Journal of Endocrinology and Metabolism
关键词
糖尿病
酮症
p细胞功能
Diabetes mellitus Ketosis β-cell function