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Explore the recovery of β-cell function in type 2 diabetic patients through continuous subcutaneous insulin infusion treatment. Investigate the potential of inducing remission and improving insulin resistance and β-cell function with long-term insulin therapy.
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Recovery of the β–cell function both in new and long-standing type 2 diabetic patients through long-term treatment with continuous subcutaneous insulin infusion Soo B Choi, Miae Kown, and Yun H noh Department of Internal Medicine and Biochemistry, School of Medicine, Konkuk University, Chungju 380-701, South Korea
Diabetes • Progressive loss of capacity to maintain glucose homeostasis • Treatment Goal • Previous concept • To slow diabetic complications • To slow the progressive loss of beta cell function • New concept • With proper treatment • The capacity can be restored or • Even Cured Holman RR. Diabetes Res Clin Pract 1998,40 (Suppl),S21
Intensive insulin treatment in type 2 diabetes • Early insulin: an important therapeutic strategy • Diabetes Care. 2005 Jan;28(1):220-1 • Intensive insulin treatment in type 2 diabetes • Diabetes Technol Ther. 2005 Oct;7(5):818-22 • Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study • Diabetes Res Clin Pract. 1995 May;28(2):103-17 • Treating the spectrum of type 2 diabetes: emphasis on insulin pump therapy • Diabetes Educ. 2006 Jan-Feb;32(1 Suppl):39S-46S • Long-term results of the Kumamoto Study on optimal diabetes control in type 2 diabetic patients • Diabetes Care. 2000 Apr;23 Suppl 2:B21-9
Induction of Long-term Normoglycemia in Type 2 DM by Intensive Insulin Therapy • Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function • Li et al: Diabetes Care. 2004 Nov. • Short-term intensive insulin therapy in newly diagnosed type 2 diabetes • Ryan et al: Diabetes Care. 2004 May. • Induction of long-term normoglycemia without medication in Korean type 2 diabetes patients after continuous subcutaneous insulin infusion therapy. • Park S, Choi SB: Diabetes Metab Res Rev 2003 May • After 2 weeks of CSII treatment • FPG 13.6 ± 4.5 mM 6.3 ± 1.3 mM • PPG 18.7 ± 6.1 mM 8.6 ± 2.3 mM • HbA1c 10.1 ± 2.2 % 8.7 ± 1.9 % • After CSII stop only exercise and diet therapy was applied • Acute insulin response (AIR), Area under the curve of insulin during IV-GTT, HOMA -B was improved
Objectives • Report • Cases of DM remission by Long-Term CSII • Analyze • Duration of treatment until remission • Change in insulin requirement during CSII • Improvement of insulin resistance and β cell function after long-term CSII
Subjects • Among the diabetic patients admitted to Diabetes Center at Konkuk University Hospital between 1996- 2005, • Patients who achieved fasting and postprandial euglycemia with only diet and exercise therapy
Remission • Maintenance of normoglycemia • Without any pharmaceutical interventions • For more than 2 months
HbA1c 8.3 ±2.9 5.9 ± 0.7 (p <0.05)
126 FPG & PP2 (mg/dl) FPG PP2 200 248 ± 153 209 ± 96 108 ± 19 126 ± 21 (p<0.05) (p<0.05)
58.5 ±40.8 0(p <0.001) Total Daily Dose of Insulin
Duration before CSIIDuration of CSIIDuration of Remission after CSIINewly Diagnosed Diabetic Patients CSII No Mx CSII No Medication No Mx CSII CSII No Mx CSII No Mx
Duration before CSIIDuration of CSIIDuration of Remission after CSIILong-standing Diabetic Patients OHA No Mx CSII OHA CSII No Mx OHA No Medication CSII No medication CSII No Mx OHA CSII OHA CSII
Duration of CSII vsDuration of Diabetes Duration of CSII (Months) R = 0.76 P = <0.01 Duration of Diabetes (Months)
Estimation of Insulin Resistance andβ Cell Function Based on C-peptide • HOMA-IR = fasting insulin x fasting glucose / 22.5 • C-peptide-IR = fasting C-peptide x fasting glucose • HOMA-β = 20x insulin / (glucose-3.5) • C-peptide-β = C-peptide / (glucose-3.5)
C-peptide-IR (Fasting) 318 ± 169 187 ± 50 (p<0.05)
C-peptide-β (Fasting) 0.347 ± 0.340 0.812 ± 0.333 (p<0.05)
C-peptide-β (Post-Prandial) 0.618 ± 0.607 1.665 ± 1.382 (p=0.065)
24.9 ±4.2 24.7 ± 3.5 (p >0.05) BMI (kg/m2) 25
Total Daily Insulin Dose and Mean Plasma Glucose M/16: Start CSII 3 days after diagnosis (%) (ng/ml) (mg/dl) C-peptide Glucose HbA1c (U/day) (U/day) (mg/ml) (mg/ml) 1st admission (2002.4.3-5.17) 2nd admission (2002.7.21-8.26) Time(days)
Summary • Remission of Diabetes • Newly diagnosed diabetic patient (n=5) • Long standing diabetic patient (n=6) • With long-term CSII • Insulin resistance is improved • Β cell function is improved • Duration of treatment until the remission seemed to be correlated with the duration of diabetes
Limitation and Future Plan • Retrospective data of remitted cases • Cannot estimate • Remission rate • Remission predictive factors → Large Scale of Prospective Cohort Study
Indication of CSII • Previous concept • T1DM • T2DM • Treatment failure with OHA and/or insulin • Labile DM • Pregnancy • After kidney transplantation • New concept • T2DM (newly diagnosed and long-standing) • Prevention of DM progression and DM complication • Improvement of β cell function and insulin resistance • CUREof diabetes