中华内分泌代谢杂志
中華內分泌代謝雜誌
중화내분비대사잡지
CHINESE JOURNAL OF ENDOCRINOLOGY AND METABOLISM
2013年
12期
1026-1030
,共5页
谭惠文%王椿%余叶蓉%喻红玲%张祥迅
譚惠文%王椿%餘葉蓉%喻紅玲%張祥迅
담혜문%왕춘%여협용%유홍령%장상신
糖尿病%酮症%β细胞功能
糖尿病%酮癥%β細胞功能
당뇨병%동증%β세포공능
Diabetes mellitus%Ketosis%β-cell function
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β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,n=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,n=10)作为对照.检测患者入院时的血糖、HbA1C、血脂、游离脂肪酸和β-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(IVGTT)、正常血糖-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AUCins0-10min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β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-高胰岛素钳夹试验结果显示,OB-KPD组GDR值为(4.91±1.82)mg·kg-1·min-1,与Lean-KPD组GDR值[(6.26± 1.89) mg·kg-·min-1]接近,KPD两组间的平均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-1·min-1,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.IVGTT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AUCins0-10min[(183.86±31.1) mIU/L]和GIR值[(2.65± 1.53) mg·kg-1·min-1]略高于Lean-KPD组[AUCins0-10min(92.1±29.8) mIU/L,GIR (2.55±1.49)mg·kg-1·min-1,P＜0.05],但显著低于OB-DM组[AUCins0-10min(697.06±231.9) mIU/L,GIR (6.53±2.21)mg· kg-1·min-1,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β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β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β细胞衰竭与高血糖和高游离脂肪酸血症有关.
目的 探討酮癥傾嚮糖尿病(KPD)患者的臨床特徵、胰島素敏感性和β細胞功能.方法 納入2004年1月至2009年12月在四川大學華西醫院內分泌科以自髮性酮癥起病的初診糖尿病(KPD)患者31例,根據體重指數分為肥胖組(OB-KPD,n=22)和體重正常組(Lean-KPD,n=9),併選擇年齡、性彆匹配的肥胖的無酮癥傾嚮初診糖尿病(OB-DM,n=10)作為對照.檢測患者入院時的血糖、HbA1C、血脂、遊離脂肪痠和β-羥丁痠水平,併檢測自身抗體包括胰島細胞抗體(ICA)、胰島素抗體(IAA)和穀胺痠脫羧酶抗體(GAD-Ab)等指標.所有受試者接受標準餐/胰島素C肽釋放試驗、靜脈葡萄糖耐量試驗(IVGTT)、正常血糖-高胰島素鉗夾試驗(EHCT)以及高血糖鉗夾試驗(HCT),以EHCT穩態期平均葡萄糖清除率(GDR)反映胰島素敏感性,以IVGTT胰島素麯線下麵積AUCins0-10min評估早相胰島素分泌反應(AIR),以HCT穩態期平均胰島素水平(Ⅰ)和穩態期平均葡萄糖輸註速率(GIR)評價胰島β細胞最大分泌功能和胰島素在體內的生物學活性.結果 KPD患者起病時均存在嚴重的高血糖和高遊離脂肪痠血癥.正常血糖-高胰島素鉗夾試驗結果顯示,OB-KPD組GDR值為(4.91±1.82)mg·kg-1·min-1,與Lean-KPD組GDR值[(6.26± 1.89) mg·kg-·min-1]接近,KPD兩組間的平均GDR值差彆無統計學意義,但均顯著低于OB-DM組患者GDR水平[(6.78±1.69)mg· kg-1·min-1,P＜0.05],提示KPD患者胰島素的介導葡萄利用率顯著下降,存在明顯的胰島素牴抗.IVGTT和HCT結果顯示:KPD患者的胰島素早相分泌和最大分泌能力均嚴重受損,OB-KPD組患者胰島素分泌的麯線下麵AUCins0-10min[(183.86±31.1) mIU/L]和GIR值[(2.65± 1.53) mg·kg-1·min-1]略高于Lean-KPD組[AUCins0-10min(92.1±29.8) mIU/L,GIR (2.55±1.49)mg·kg-1·min-1,P＜0.05],但顯著低于OB-DM組[AUCins0-10min(697.06±231.9) mIU/L,GIR (6.53±2.21)mg· kg-1·min-1,P＜0.01].結論 KPD患者起病急性期存在嚴重的糖脂代謝紊亂和胰島素牴抗,併存在不同程度的β細胞功能受損.肥胖KPD患者外週胰島素牴抗更嚴重,超過體重指數與之接近的OB-DM組,但Lean-KPD患者β細胞功能受損程度更為突齣.KPD患者的嚴重外週胰島素牴抗和β細胞衰竭與高血糖和高遊離脂肪痠血癥有關.
목적 탐토동증경향당뇨병(KPD)환자적림상특정、이도소민감성화β세포공능.방법 납입2004년1월지2009년12월재사천대학화서의원내분비과이자발성동증기병적초진당뇨병(KPD)환자31례,근거체중지수분위비반조(OB-KPD,n=22)화체중정상조(Lean-KPD,n=9),병선택년령、성별필배적비반적무동증경향초진당뇨병(OB-DM,n=10)작위대조.검측환자입원시적혈당、HbA1C、혈지、유리지방산화β-간정산수평,병검측자신항체포괄이도세포항체(ICA)、이도소항체(IAA)화곡알산탈최매항체(GAD-Ab)등지표.소유수시자접수표준찬/이도소C태석방시험、정맥포도당내량시험(IVGTT)、정상혈당-고이도소겸협시험(EHCT)이급고혈당겸협시험(HCT),이EHCT은태기평균포도당청제솔(GDR)반영이도소민감성,이IVGTT이도소곡선하면적AUCins0-10min평고조상이도소분비반응(AIR),이HCT은태기평균이도소수평(Ⅰ)화은태기평균포도당수주속솔(GIR)평개이도β세포최대분비공능화이도소재체내적생물학활성.결과 KPD환자기병시균존재엄중적고혈당화고유리지방산혈증.정상혈당-고이도소겸협시험결과현시,OB-KPD조GDR치위(4.91±1.82)mg·kg-1·min-1,여Lean-KPD조GDR치[(6.26± 1.89) mg·kg-·min-1]접근,KPD량조간적평균GDR치차별무통계학의의,단균현저저우OB-DM조환자GDR수평[(6.78±1.69)mg· kg-1·min-1,P＜0.05],제시KPD환자이도소적개도포도이용솔현저하강,존재명현적이도소저항.IVGTT화HCT결과현시:KPD환자적이도소조상분비화최대분비능력균엄중수손,OB-KPD조환자이도소분비적곡선하면AUCins0-10min[(183.86±31.1) mIU/L]화GIR치[(2.65± 1.53) mg·kg-1·min-1]략고우Lean-KPD조[AUCins0-10min(92.1±29.8) mIU/L,GIR (2.55±1.49)mg·kg-1·min-1,P＜0.05],단현저저우OB-DM조[AUCins0-10min(697.06±231.9) mIU/L,GIR (6.53±2.21)mg· kg-1·min-1,P＜0.01].결론 KPD환자기병급성기존재엄중적당지대사문란화이도소저항,병존재불동정도적β세포공능수손.비반KPD환자외주이도소저항경엄중,초과체중지수여지접근적OB-DM조,단Lean-KPD환자β세포공능수손정도경위돌출.KPD환자적엄중외주이도소저항화β세포쇠갈여고혈당화고유리지방산혈증유관.
Objective To investigate the clinical characteristics,peripheral insulin sensitivity,and β-cell function in patients with ketosis-prone diabetes(KPD).Methods Thirty-one patients with newly diagnosed ketosisprone 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 ≥ 25 kg/m2,n =22) and Lean-KPD (BMI ＜ 23 kg/m2,n =9).10 patients with newly-onset type 2 diabetes free from ketosis (OB-DM:BMI ≥ 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 min) during IVGTT.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 1 · min-1 in subjects with OB-KPD,being lower than that in Lean-KPD patients[(6.26 ± 1.89) mg · kg 1 · min-1] and OB-DM group[(6.78-± 1.69) mg · kg 1 · min-1,P＜0.01].Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients.Area under the insulin curve [AUCins0-10min (183.86 ± 31.1) mIU/L] and GIR[(2.65 ±1.53) mg · kg-1 · min-1] in OB-KPD patients were lower than those in OB-DM group[(697.06-± 231.9) mIU/L,(6.53 ± 2.21)mg · kg 1 · min-1,P＜0.0 1],but slightly higher than the Lean-KPD group [AUCins0 10min (92.1 ±29.8) mUU/L,GIR (2.55 ± 1.49) mg · kg 1 · min-1,P＜0.05].Glucose disposal rate (GDR) was strongly associated with casual plasma glucose (r =-0.502,P＜0.01),HbA1C(r =-0.553,P＜0.0 1) and FFA eoneentrations (r=-0.504,P＜0.01) on admission.Conclusions Insulin resistance and β-cell dysfunction coexist in all KPD patients.OB-KPD patients exhibit more severe insulin resistance,while Lean-KPD patients have lower insulin secretion.KPD patients had severe hyperglycemia,hypertriglyceridemia,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 patients with KPD.
