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 , 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 Jan;28(1):220-1 Intensive insulin treatment in type 2 diabetes –Diabetes Technol Ther Oct;7(5): Intensive insulin therapy prevents the progression of dia betic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomiz ed prospective 6-year study –Diabetes Res Clin Pract May;28(2): Treating the spectrum of type 2 diabetes: emphasis on insulin pump therapy –Diabetes Educ 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 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 Nov. Short-term intensive insulin therapy in newly diagnosed type 2 diabetes –Ryan et al: Diabetes Care 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 , 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

Overview Sex Age Initial BMI (kg/m 2 ) Therapy before CSII Duration (months) HbA1c (%)FPG (mg/dl)PP2 (mg/dl) before CSII of CSII remiss ion before CSII at present before CSII at present before CSII at present M1625.2None M NPH M4230.8None F2120.6None F5629.7None F4920.3OHA F5629.6OHA M5420.5None F6123.0OHA M5120.8OHA F6425.5OHA

HbA1c 8.3 ± ± 0.7 (p <0.05)

FPG & PP2 209 ± ± ± ± 21 (p<0.05) (mg/dl) FPG PP

Total Daily Dose of Insulin 58.5 ±40.80 (p <0.001)

Duration before CSII Duration of CSII Duration of Remission after CSII Newly Diagnosed Diabetic Patients CSII No Medication No Mx

Duration before CSII Duration of CSII Duration of Remission after CSII Long-standing Diabetic Patients OHA CSII OHA No medication No Medication No Mx CSII No Mx No Mx

Duration of CSII vs Duration of Diabetes (Months) Duration of Diabetes Duration of CSII R = 0.76 P = <0.01

Estimation of Insulin Resistance and β 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 ± ± 50 (p<0.05)

C-peptide-β (Fasting) ± ± (p<0.05)

C-peptide-β (Post-Prandial) ± ± (p=0.065)

BMI (kg/m 2 ) ± ± 3.5 (p >0.05)

Total Daily Insulin Dose and Mean Plasma Glucose M/16: Start CSII 3 days after diagnosis Time(days) (U/day)(mg/ml) 2 nd admission ( ) (U/day) (mg/ml) 1 st admission ( ) HbA1c (%) FPG (mg/dl) PP2 (mg/dl) C-peptide (ng/ml) FastingPostprandial Before CSII months after CSII Stop HbA1c (%) Glucose (mg/dl) C-peptide (ng/ml)

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 CURE of diabetes