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Comparison of two insulin regimens in type-2 diabetes concerning metabolic control and body weight
Track 2. Clinical Research & Care increment between 0.00 b and 6.00 h a.m. was ~2 mmol/l, additional 4 to 8 LU. of insulin at 2.00 a.m. were given to prevent this dawn phenomenon. Consequently, the patients were controlled in their local centers. Recently, a total of 272 patients from 3 different centers (Ctr. A,B,C) were checked and those having complete data (n=70, age 54.7f1.37 years, diabetes duration 1 l.Of1.05 years) were evaluated by means of the paired t-test and the analysis of variance. The results are shown as mean&SE Results: At the end of the observation period (5f0.12 years), 96% of patients continued the CIT with 4 to 7 insulin boluses/d and selfmonitoring. The BMI and HbAlc decreased together with a reduction of insulin/d in the center C. See Table for details. cu. A
”
Parameter BMI[kg/m’]
Stan
End
29.8zt1.60
31.4f1.60
P
A A
13 13 13
HbAlc [%I Insulin [LUld]
8.4f0.59 48.8f5.83
9.2f0.43 48.1zk5.2
NS NS
B B
22 22
BMI[kg/m’] HbAlc (%]
31.2i1.49 9.3io.50
30.2f1.39 10.8f0.41
B
22
Insulin [l.U./d]
54.4f5.38
53.3zk5.05
0.05 co.01 NS
C C C
35
BMI[kg/m*] HbAIc [%I Insulin [I.U./d]
29.1f0.81
28.1ztO.86
10.4f0.51 37.2f3.09
7.6h0.23 28.6f1.50
35 35
Conclusions: In educated obese type 2 diabetic patients the CIT may result in reduction of insulin requirements and in reduction of body mass and HbAlc. The acceptance of CIT was 96%.
P318 Testing tbe Concept of Administering Thrice Daily Premixed Insulin Aspart in ‘Qpe 2 Diabetes JENS SANDAHL CHRISTIANSEN’, Niels Ejskjaer’, Merete Rasmussen2, Niels Kampz, Anders Lindholm*, Jens Otto Jorgensen ’ ’ Dept. Endocrinology M, Aarhus Univ Hospital, Aarhus, Denmark: ’ Clinical Development, Novo Nordisk A/S, Bagsvaerd, Denmark Purpose Biphasic insulin aspart 50 and 70 (BIAsp 50 and 70) consist of 50% and 70% soluble insulin aspart (IAsp) combined with 50% and 30% protamine-crystallised IAsp, respectively. These new premixed insulin aspart were administered in a thrice daily treatment regimen before each main meal as the sole treatment thereby testing the glycaemic control without administration of additional NPH-insulin. Methods 16 type 2 diabetic patients (n=8/50% male, n=8/50% female; age: 59.3f8.1 yrs; BMI 27.7f2.8 kg/m2; diabetes duration 12.3f4.9 yrs) were treated with twice daily biphasic human insulin(BHD20 or 30 during run-in and randomized to either BIAsp 70 TID (Dinner 70) for 4 weeks or 4 weeks treatment with BIAsp 70 at breakfast and lunch and BIAsp 50 at dinner (Dinner 50) in a cross-over design. The total daily insulin dose taken at the end of run-in was the same at the beginning of each treatment period but divided into three doses. Glycaemic control was assessed by fasting serum glucose, 24-hour glucose and insulin profiles at baseline (run-in) and after each of the two treatment periods. Results The average serum glucose concentration between 08.00 and 22.00 hours showed a significantly better control in Dinner 70 versus run-in (mean difference 1.60 nnnol/l, 95% C.I. [0.25-2.951, p-value < 0.05) but no difference in control in Dinner 50 versus run-in. The average serum glucose control between 22.00 and 08.00 hours did not differ between the treatments. However, fasting blood glucose was higher with Dinner 70 as well as 50 versus run-in with mean glucose values of 7.8 mmol/l (run-in), 10. 2 mmol/l (Dinner 70) and 10.7 mmolil (Dinner 50), (Dinner 70/run-in ratio 0.73,95% C.I. [0.63-0.841, p-value < 0.01; Dinner 50/run-in ratio 0.75, 95% C.I. [O&t-0.88], p-value < 0.01). No major hypoglycaemic episodes occurred during the trial. Conclusions The new treatment concept of thrice daily BIAsp 70 administration provides an improved daytime control to twice daily BHI. Post-prandial glucose control after lunch was significantly improved in
S61
both BIAsp treatment groups compared to BHI. For optimization of the nighttime control however, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin.
P319 Comparison of Two Insulin Regimens in Type-2 Diabetes Concerning Metabolic Control and Body Weight B. WILLMS, R. Pabst, C. Nagel-Reuper, W. Schriiter, R. Liibben. DiabeteszentrumBad Lauterberg, Germany Problem: A common side-effect of conventional insulin treatment in type-2 diabetic patients is an increase of body weight, often accompanied by elevation of blood pressure as well as an increase of serum lipids. In this study we investigated, if intensive insulin therapy has advantages concerning body weight, blood glucose control, and serum lipids compared with conventional insulin therapy. Methods: In 100 Patients with type-2 diabetes, who were unsatisfactory controlled with diet and oral antidiabetics, insulin therapy was started in randomised order. Group 1: A fixed insulin combination of regular and NPH-insulin (30/70) given twice daily. Group 2: Injection of the insulinanalogon Lispro three times per day and one injection of NPH-insulin at bedtime. HBAt,, body weight, blood lipids and insulin doses were measured in 3-month intervalls. Results: After 6 months the following changes were observed: HBAt, in group 1 decreased from lo,88 to 8,45% (A HBA,, = -2,43, p < 0.0001); in group 2 from lo,47 to 7,618 (A HBAt, = -2.86, p < 0,OOOl). Body weight in group 1 increased from 82,0 to 87.7 kg (A weight gain = +5,7 kg, p < 0.0001). In group 2 there was an increase from 83,3 to 86.8 kg (A weight gain = +3,5 kg, p < 0,OOOl). The difference between both groups was significant (p = 0,004). Insulin requirements were comparable in both groups. Serum cholesterol was similar in both groups, LDL-cholesterol being slightly lower in group 2. Conclusion: After 6 months, patients using the intensified insulin regimen showed significant less weight gain and a greater decrease of HBA,,. In the intensified group, the changes of LDL- and HDL-cholesterol resulted into a better lipid profile.
P320 Combined Therapy of Diabetes Mellitos ‘Qpe~2 by Intermediate Acting Insulin and Acarbosis M. KOSELJ. Department of Diabetes and Endocrinology, Universiry Medical Centre Ljubljann, Slovenia The aim: The study tried to determine whether acarbosis could replace or decrease the dose of short acting insulin in patients with diabetes mellitus type 2, treated with short and intermediate acting insulin once or twice daily. Patients and methods: 23 patients with diabetes mellitus type 2 were included in the study. They were all treated with intermediate and short acting insulin once or twice daily, the total daily dose being lower than 80 IU. Duration of the study was 24 weeks. In the first 8 weeks we tried to regulate diabetes mellitus with insulin only. In the following 4 weeks acarbosis was added to therapy, in increasing dosages up to 300 mg daily. Simultaneously dosages of insulin were reduced. In weeks 12-24 21 patients were administered with combination of acarbosis and intermediate acting insulin, while other two patients received additional, but minimal dosages of short acting insulin. Blood glucose (BG), body weight and HbAlc were checked on monthly basis and hypoglycemias were registered. Three days before a check up patients performed the 10 point profile. Two patients were excluded from the study on account of serious adverse events due to treatment with acarbosis.
”
Parameter BMI[kg/m’]
Stan
End
29.8zt1.60
31.4f1.60
P
A A
13 13 13
HbAlc [%I Insulin [LUld]
8.4f0.59 48.8f5.83
9.2f0.43 48.1zk5.2
NS NS
B B
22 22
BMI[kg/m’] HbAlc (%]
31.2i1.49 9.3io.50
30.2f1.39 10.8f0.41
B
22
Insulin [l.U./d]
54.4f5.38
53.3zk5.05
0.05 co.01 NS
C C C
35
BMI[kg/m*] HbAIc [%I Insulin [I.U./d]
29.1f0.81
28.1ztO.86
10.4f0.51 37.2f3.09
7.6h0.23 28.6f1.50
35 35
Conclusions: In educated obese type 2 diabetic patients the CIT may result in reduction of insulin requirements and in reduction of body mass and HbAlc. The acceptance of CIT was 96%.
P318 Testing tbe Concept of Administering Thrice Daily Premixed Insulin Aspart in ‘Qpe 2 Diabetes JENS SANDAHL CHRISTIANSEN’, Niels Ejskjaer’, Merete Rasmussen2, Niels Kampz, Anders Lindholm*, Jens Otto Jorgensen ’ ’ Dept. Endocrinology M, Aarhus Univ Hospital, Aarhus, Denmark: ’ Clinical Development, Novo Nordisk A/S, Bagsvaerd, Denmark Purpose Biphasic insulin aspart 50 and 70 (BIAsp 50 and 70) consist of 50% and 70% soluble insulin aspart (IAsp) combined with 50% and 30% protamine-crystallised IAsp, respectively. These new premixed insulin aspart were administered in a thrice daily treatment regimen before each main meal as the sole treatment thereby testing the glycaemic control without administration of additional NPH-insulin. Methods 16 type 2 diabetic patients (n=8/50% male, n=8/50% female; age: 59.3f8.1 yrs; BMI 27.7f2.8 kg/m2; diabetes duration 12.3f4.9 yrs) were treated with twice daily biphasic human insulin(BHD20 or 30 during run-in and randomized to either BIAsp 70 TID (Dinner 70) for 4 weeks or 4 weeks treatment with BIAsp 70 at breakfast and lunch and BIAsp 50 at dinner (Dinner 50) in a cross-over design. The total daily insulin dose taken at the end of run-in was the same at the beginning of each treatment period but divided into three doses. Glycaemic control was assessed by fasting serum glucose, 24-hour glucose and insulin profiles at baseline (run-in) and after each of the two treatment periods. Results The average serum glucose concentration between 08.00 and 22.00 hours showed a significantly better control in Dinner 70 versus run-in (mean difference 1.60 nnnol/l, 95% C.I. [0.25-2.951, p-value < 0.05) but no difference in control in Dinner 50 versus run-in. The average serum glucose control between 22.00 and 08.00 hours did not differ between the treatments. However, fasting blood glucose was higher with Dinner 70 as well as 50 versus run-in with mean glucose values of 7.8 mmol/l (run-in), 10. 2 mmol/l (Dinner 70) and 10.7 mmolil (Dinner 50), (Dinner 70/run-in ratio 0.73,95% C.I. [0.63-0.841, p-value < 0.01; Dinner 50/run-in ratio 0.75, 95% C.I. [O&t-0.88], p-value < 0.01). No major hypoglycaemic episodes occurred during the trial. Conclusions The new treatment concept of thrice daily BIAsp 70 administration provides an improved daytime control to twice daily BHI. Post-prandial glucose control after lunch was significantly improved in
S61
both BIAsp treatment groups compared to BHI. For optimization of the nighttime control however, the dinner dose needs adjustment or replacement by a premixed insulin with a larger proportion of basal insulin.
P319 Comparison of Two Insulin Regimens in Type-2 Diabetes Concerning Metabolic Control and Body Weight B. WILLMS, R. Pabst, C. Nagel-Reuper, W. Schriiter, R. Liibben. DiabeteszentrumBad Lauterberg, Germany Problem: A common side-effect of conventional insulin treatment in type-2 diabetic patients is an increase of body weight, often accompanied by elevation of blood pressure as well as an increase of serum lipids. In this study we investigated, if intensive insulin therapy has advantages concerning body weight, blood glucose control, and serum lipids compared with conventional insulin therapy. Methods: In 100 Patients with type-2 diabetes, who were unsatisfactory controlled with diet and oral antidiabetics, insulin therapy was started in randomised order. Group 1: A fixed insulin combination of regular and NPH-insulin (30/70) given twice daily. Group 2: Injection of the insulinanalogon Lispro three times per day and one injection of NPH-insulin at bedtime. HBAt,, body weight, blood lipids and insulin doses were measured in 3-month intervalls. Results: After 6 months the following changes were observed: HBAt, in group 1 decreased from lo,88 to 8,45% (A HBA,, = -2,43, p < 0.0001); in group 2 from lo,47 to 7,618 (A HBAt, = -2.86, p < 0,OOOl). Body weight in group 1 increased from 82,0 to 87.7 kg (A weight gain = +5,7 kg, p < 0.0001). In group 2 there was an increase from 83,3 to 86.8 kg (A weight gain = +3,5 kg, p < 0,OOOl). The difference between both groups was significant (p = 0,004). Insulin requirements were comparable in both groups. Serum cholesterol was similar in both groups, LDL-cholesterol being slightly lower in group 2. Conclusion: After 6 months, patients using the intensified insulin regimen showed significant less weight gain and a greater decrease of HBA,,. In the intensified group, the changes of LDL- and HDL-cholesterol resulted into a better lipid profile.
P320 Combined Therapy of Diabetes Mellitos ‘Qpe~2 by Intermediate Acting Insulin and Acarbosis M. KOSELJ. Department of Diabetes and Endocrinology, Universiry Medical Centre Ljubljann, Slovenia The aim: The study tried to determine whether acarbosis could replace or decrease the dose of short acting insulin in patients with diabetes mellitus type 2, treated with short and intermediate acting insulin once or twice daily. Patients and methods: 23 patients with diabetes mellitus type 2 were included in the study. They were all treated with intermediate and short acting insulin once or twice daily, the total daily dose being lower than 80 IU. Duration of the study was 24 weeks. In the first 8 weeks we tried to regulate diabetes mellitus with insulin only. In the following 4 weeks acarbosis was added to therapy, in increasing dosages up to 300 mg daily. Simultaneously dosages of insulin were reduced. In weeks 12-24 21 patients were administered with combination of acarbosis and intermediate acting insulin, while other two patients received additional, but minimal dosages of short acting insulin. Blood glucose (BG), body weight and HbAlc were checked on monthly basis and hypoglycemias were registered. Three days before a check up patients performed the 10 point profile. Two patients were excluded from the study on account of serious adverse events due to treatment with acarbosis.