2 2 2 1997 Hasan Ilkova 2-22 2 15 7 46.3 12.9 BMI 25.92 3.59 Kg/m 2 10.96 2.28mmol/l 2 21.17 3.01mmol/l 10.28 1.56% 2 2 Homa B p<0.05 Homa A p<0.05 r=0.521 p=0.013 15 6 5.97±0.59% 6.34±1.07mmol/l OGTT2 7.81±2.41mmol/l 8.63±4.43uU/ml OGTT2 19.85±5.33uU/ml 2-2 [ ] 2 1
Induction of long-term good glycermic control in newly diagnosed Type 2 diabetic patients by transient intensive insulin treatment Author: Zhu Fang Superviser: Mao Tengshu Ji Linong Department of endocrinology and metabolism, People s Hospital The graduated Institute, Peking University Health science Center Abstract Type 2 diabetes is a slowly progressive disease, in which the gradual deterioration of glucose tolerance is associated with the progressive decrease in -cell function. Human studies support the critical physiologic role of the first-phase of insulin secretion in the maintenance of postmeal glucose homeostasis. In the early stages of type 2 diabetes, first-phase insulin release is almost invariably lost. The deficiency of the first-phase of insulin secretion is associated with the progression from NGT to IGT and from IGT to DM. Some studies have found that the first-phase of insulin secretion hadn t improved significantly via the treatment including diet control and/or hypoglycemic agent or insulin. In 1997, Hasan Ilkova had found that the short-term intensive insulin treatment could lead to long-term good glycemic control without medication in some type 2 diabetes patients, but the mechanism underline it has not been explored. We hypothesized that the transient intensive insulin treatment can improve -cell function and restore the first-phase of insulin secretion via eliminating the glucose toxicity. To test this hypothesis, we evaluated -cell function and correlated factors by observing the variance of the first-phase of insulin response to intravenous glucose before and after transient intensive insulin treatment in newly diagnosed type 2 diabetic patients and followed up patients for their glycemic control level. Research design and methods: Twenty-two newly diagnosed type 2 diabetic patients(15 men and 7 women) with a mean±se age of 46.3 12.9 years and BMI of 25.92 3.59 Kg/m 2 participated in the study. Patients had fasting plasma glucose levels of 10.96 2.28 mmol/l, 2-h post-prandial glucose levels of 21.17 3.01 mmol/l, glycated hemoglobin levels of 10.28 1.56%.Patients were admitted to the hospital and treated with continuous subcutaneous insulin infusion (CSII) for 2 weeks. Before and after the treatment, they were carried out the intravenous glucose tolerance test. And they followed longitudinally while being treated with diet alone. Results: Two weeks after the treatment, the AUC 0-10 INS, the insulin peak, the increment of the insulin peak( INS), the 2
total amount ratio of insulin and glucose, the ratio of INS/ G and Homa B were significantly increased, p<0.05. Homa A was also significantly decreased, p<0.05. The insulin peak before and after the treatment has the positive correlation, r=0.521 p=0.013. Fifteen patients were followed up for an average of 6 months with mean HbA 1 c of 5.97±0.59%, fasting plasma glucose levels of 6.34±1.07 mmol/l, 2-h OGTT plasma glucose levels of 7.81±2.41 mmol/l, fasting insulin levels of 8.63±4.43 uu/ml and 2-h OGTT insulin levels of 19.85±5.33 uu/ml. Short-term intensive insulin treatment can effectively induced long-term good glycemic control without medication by improving the -cell function as well as decreasing the insulin resistance and restoring the first-phase of insulin secretion via eliminating the glucose toxicity, the patient may be brought back in time along the natural history of type 2 diabetes to a stage where non-pharmacological therapeutic measures are still quite efficacious, suggesting that the transient intensive insulin treatment might be used as primary approach in the management newly diagnosed type 2 diabetes patients. [key words]: type 2 diabetes, insulin, the first-phase secretion, 3
intensive treatment 2 1.35 2 2 [1] 2 1 2 3 2 [2 3] 2 Kosaka et al OGTT [4] [5] [6] [7] Lispro [8] 1997 Hasan 13 2 2 5 2 [9] 2 2 - - - 4
2,,,,, 1.35 2 1995 20 4.0% 2025 5.4% 3 WHO 42% 5 1 7 2 170% 8 4 2 2 8 [10] 2 1. 2. 3. 4. 2 2 [11,12] 2 [13,14] 95% [15,16] 2 4 [17,18] 2 2 [ ] [19] [20] 10 2 ATP ATP/ADP ATP K + Ca 2+ Ca 2+ <5% >95% ATP [21] 2+ Na + /Ca 2+ Ca 2+ Ca 2+ A Ca 2+ C 5
I GLP-1 [22] GLP-1 GLP-1 c-amp c-amp A [23] [24-29] 5-15 120 [30-37] 70% [31,38] [37,39-41] I I [42,43] 10% [44] [45,46] [44,45,47,48] 3 PC3 PC2 H [44,45] PC3 32 33 PC2 H C [2 ] 2 HomaA ISI HomaB [49-51] 1. 2 CAPN10 HDL [10] 6
7 2 2 IGT 2 [52] IGT 2 2 IGT 2 2 2 Pima --- 30-40 [13,53-55] --- [56] 2 1
1. 2 [2 ] 2 [57] [58] 1 2 5.6mmol/l 6.4mmol/l [52] mrna 8
9 mrna [59] ZDF [60,61] GK 2 2 2 1
1. - -2 Ca 2+ -ATP -3-2 6- c-myc Ca 2+ -ATP-2B - 2 6-12- -2 - -1 Weir and Bonner-Weir [57],Jonas et al [62], and Laybutt et al [63,64]. 10
[2 ] 2 1 2 [1] [65-70] 2 20-40% [71] I 90% 2 [72] [73-79] 2 I [80-82] I [83-90] [91] PC3 PC2 H PC3 PC2 H 32 33 [44,45,92] ATP 6 2 6 ATP/ADP ATP K + [21] [93] [25,94-96] 11
Na + Ca 2+ Ca 2+ Ca 2+ [97] 2-6- C c-myc p21 p27 2. 2 [98-100] A CPT-1 A [98-102] A C A Ca 2+ -ATPase Ca 2+ [98,102-106] A K [93] Ca 2+ A 2 A A CPT-1 [107] A A ATP CPT-1 A [98,102,107-109] 12
mtdna3243 A-G [110-10113] MtDNA16189 T-C 2 [114] SUR SUR 24 2 [115] SUR 2 [116] MODY MODY 1997 MODY [117] MODY1 20 HNF-4α [118] MODY2 7 GCK [119] MODY3 12 HNF-1α [120] MODY4 13 [121] MODY5 17 HNF-1 [122] NeuroD1/BETA2 Joslin NEUROD1 E2A E47 E-box [123] GLUT2 2 2 35-40% [124-130] [131,132] [133,134] [126,135-137] [125,138,139] [140,141] [142-144] [145,146] 2 I 4 [147] [148] [149-157] 2 [98] A [158] CAPN10 I II RAD TNF- CAPN10 2 [159,160] 13
[ ] 1940 Haist et al [161] 50 Dohlan Lukens [162] Leahy [163] 5.5mmol/l [164] Kosaka [4] 4.4mmol/l 7.8mmol/l 7.8mmol/l [165] 3 (uu/ml) 20 15 10 5 60 140 220 300 (mg/dl) 3. 2 13.9mmol/l 16.7mmol/l [166,167] [124,168] [24,25, 45, 124, 157, 168-170] - [171] 4 [172] 14
8 (mg/kg.min) 4 20 40 60 80 100 Basal Basal (uu/ml) 4. ( 2 ) [173] 2 [174] 2 [175] 2 [176,177] 70% [171] Ca 2+ [178] 2 [179] [180] Gerich IGT [181] OGTT 30 2 Steiner [182] Pima Indians 2 [183] [184-186] [187,188] [171] DCCT UKPDS 2 [189] 15
2. 5 [190] C 2 Na + -K + ATPase 5. (NADPH) [191] Na + /K + ATPase Schiff amadori [192] [193,194] [195] PKC 2 PKC I IV C 16