＂蜜月期＂胰岛功能对初发糖尿病合并酮症患者分型和预后的意义

The classification and prognostic implication of islet β cell function before and in remission period in newly diagnosed diabetic patients with ketosis

目的 观察进入＂蜜月期＂的初发糖尿病合并酮症患者的胰岛功能恢复情况及对糖尿病分型的意义.方法 初发糖尿病合并酮症患者住院胰岛素强化治疗后,对其中206例进入＂蜜月期＂患者随访36个月,依据是否需要长期胰岛素强化治疗分为2组,其中19例在＂蜜月期＂后必须应用强化胰岛素治疗才能良好控制血糖（A组）,界定为1型糖尿病；其他187例在＂蜜月期＂结束后不需要应用胰岛素强化治疗（B组）,界定为2型糖尿病.比较两组胰岛素强化治疗前后胰岛功能的变化、＂蜜月期＂持续时间,并分析其对糖尿病分型及预后治疗方案选择的意义.结果 胰岛素强化治疗前和治疗后A组胰岛素曲线下面积（ AUCI）、C肽曲线下面积（AUCC）及稳态模型评估法（HOMA）评价的胰岛β细胞基础功能（HOMA-β）和胰岛素抵抗指数（HOMA-IR）均明显低于B组[治疗前分别为（10.18±2.36）mIU·h·L-1比（20.28 ±6.89）mIU·h·L-1,（1.56 ±0.53） μg·h·L-1比（3.75±0.67） μg·h·L-1,3.68±1.08比18.20±6.59,1.22 ±0.49比3.06 ±1.54;治疗后分别为（29.86±8.65）mIU·h·L-1比（ 93.35 ±19.42） mIU·h·L-1,（3.99±0.79）μg·h·L-1比（12.54 ±3.83）μg·h·L-1,8.50±2.46比56.17±19.42,0.63±0.56比1.42 ±0.78],A组年龄、BMI、有糖尿病家族史比例更低,无合并高血压、高脂血症等代谢综合征情况.A组＂蜜月期＂持续时间明显短于B组[（7.9±5.2）个月比（20.9±9.9）个月].糖尿病相关抗体检测的阳性率不高,与临床结局符合率低.强化治疗后复查胰岛素释放试验：A组胰岛素、C肽释放高峰提前,出现在服葡萄糖水后0.5～1 h,但在口服葡萄糖刺激后的胰岛素、C肽释放最高峰不到基础值的2倍；而B组的胰岛素、C肽释放高峰出现在口服葡萄糖水后1h或2h,在口服葡萄糖刺激后的胰岛素、C肽释放最高峰是基础值的4～10倍.结论 进入＂蜜月期＂的初发糖尿病合并酮症患者中91％为2型糖尿病；强化胰岛素治疗前胰岛功能差、强化治疗后恢复不充分、＂蜜月期＂持续的时间短暂是1型糖尿病的标志.

Objective To observe β cell function in newly diagnosed diabetic patients with ketosis before and in remission period and evaluate its classification and predictive value.Methods A total of 206 patients newly diagnosed as diabetic ketosis who had been treated with intensive insulin therapy in our hospital and entered in the ＂honeymoon＂ after the withdraw of insulin therapy were followed for 36 months from onset of diabetes.They were divided into two groups of type 1 and type2 diabetes （ group A and B）,according to the dependence or independence on insulin treatment. The β cell function of the two groups before and in remission period was compared by oral glucose tolerance test （OGTF）.β cell function was measured with the AUC of insulin and C-peptide and homeostatic model assessment β-cell function （HOMA-β）,while homeostatic model assessment insulin resistant （HOMA-IR） for insulin resistant.The duration of the ＂honeymoon＂ and the change of insulin and C-peptide curve before and in ＂honeymoon＂ were also observed.Results The AUC of insulin and C-peptide,the HOMA-β and the HOMA-IR before and after the intensive insulin treatment were lower in group A than that in group B [ before the insulin treatment：（10.18 ±2.36）mIU · h · L-1 vs （20.28 ±6.89）mIU · h · L-1,（1.56 ±0.53） μg · h · L-1 vs （3.75 ±0.67） μg · h · L-1,3.68 ± 1.08 vs 18.20 ±6.59,1.22 ±0.49 vs 3.06 ± 1.54,respectively;after the insulin treatment：（29.86 ± 8.65 ） mIU · h · L-1 vs （93.35 ± 19.42 ） mIU · h · L-1,（ 3.99 ± 0.79 ）μg · h · L-1 vs （ 12.54 ±3.83） μg · h · L-1,8.50 ±2.46 vs 56.17 ± 19.42,0.63 ±0.56 vs 1.42 ±0.78,respectively ].The duration of the ＂honeymoon＂ in group A was significantly shorter than in group B [ （7.9 ±5.2） months vs （20.9 ± 9.9 ） months ].In oral glucose insulin and C-peptide release test,the peak of insulin and C-peptide releasing curve in group A was brought forward by a half to 1 hour after intensive treatment while delayed in group B by 1 or 2 hours.The releasing peak of insulin and C-peptide in group A was less than two folds of the basic value,while four to ten fold of the basic value in group B.The positive ratio of glutamic acid decarboxylase antibody,insulin autoantibody and insular cellular antibody in group A and group B were 21.2% vs 4.8%,18.1% vs 3.3%,9.2% vs 10.6%,respectively.Conclusions Of all the patients newly diagnosed as diabetes ketosis who had entered into the honeymoon after intensive insulin therapy,91% were type 2 diabetes.Inferior β cell function before insulin therapy,weaker remission after insulin therapy and shorter duration of remission period suggest the classification of type 1 diabetes.