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Control of metabolic syndrome with metformin in obese type 2 diabetes mellitus patients
Track 2. Clinical Research & Care in type 2 diabetes. Patients (n=806) were randomly assigned to receive placebo, glyburide 2.5 mg, metformin 500 mg, M/G 250 mg/1.25 mg, or M/G 500 mg/2.5 mg. Doses were titrated over an 8-week period based on glycemic response. Patients receiving M/G 250 mg/1.25 mg achieved a mean decrease of 1.66% in HbAlc compared with 1.34%, 0.90%, and 1.70% for glyburide, metformin, and M/G 500 mg/2.5 mg, respectively. These findings suggest a synergistic effect, with M/G tablets achieving glycemic control at lower doses than either glyburide or metformin as first-line treatment in type 2 diabetes.
P265 Metformin/Glyburide Tablets as First-Line Treatment in Type 2 Diabetes: Distribution of HbA~ Response JAIME A. DAVIDSON l, Alan Garber 2, Arshag D. Mooradian 3, Stephen Schneider 4, David Henry z. 1 Endocrine & Diabetes Association of Texas, Dallas, TX, United States of America; 2 Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ, United States of America; 3Division of Endocrinology, St Louis University School of Medicine, St Louis, MI, United States of America; 4 Robert Wood Johnson Medical School, Piscataway, NJ, United States of America The pathogenesis of type 2 diabetes involves both impaired insulin secretion and increased insulin resistance. Use of two oral antidiabetic agents with complementary mechanisms of action may result in a greater response than either drug alone. This multicenter study evaluated the efficacy of two metformin/glyburide (M/G) tablet dosages after 20 weeks of oral administration as first-line therapy. Patients (n=806) were randomly assigned to receive placebo, glyburide (2.5 mg), metformin (500 mg), or M/G tablets (250 mg/1.25 mg or 500 mg/2.5 mg). Doses were titrated over an 8-week period based on glycemic response. A greater percentage of patients in the M/G 250 mg/l.25 mg (66%) and M/G 500 mg/2.5 mg (72%) treatment groups achieved hemoglobin Arc levels of less than or equal to 7% compared with placebo (20%), glyburide (60%), and metformin (50%) at Week 20. HbAic%
Absolute <7.0 7.1-7.9 >8.0 Decrease <0.5 0.5-0.9 1.0-1.4 1.4-1.9 >2.0
Placebo n=147 n(%)
Gly 2.5 mg n=142 n(%)
Met500mg n=141 n(%)
M/G 25~1.25 n=149 n(%)
M/G 5(}0/2.5 n=152 n(%)
29 (20) 55 (37) 63 (43)
85 (60) 37 (26) 20 (14)
71 (50) 42 (30) 28 (20)
99 (66) 38 (26) 12 (8)
109 (72) 29 (19) 14 (9)
98 (67) 24 (16) 15 (10) 5 (3) 5 (3)
28 (20) 32 (23) 28 (20) 30 (21) 24 (17)
39 (27) 35 (25) 26 (18) 20 (14) 22 (16)
28 (19) 23 (15)
21 (14) 24 (16) 32 (21) 32 (21) 43 (28)
26 (17) 42 (28)
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the mean age:49.8+9.1 yrs) (Group II) and 10 subjects BMI>25kg/m 2 with impaired glucose tolerance (IGT) (4 male, 6 female; the mean age:41.3-4-11.1yrs) (Group III) to determine the effect of 12 weeks of treatment with metformin 2.5g/day on insulin resistance and lipid profiles. Before and after treatment sistolic and diastolic blood pressure, waist-hip ratio, serum total cholesterol, HDL-cholesterol, triglyceride, apoprotein A1, apoprotein B and the insulin resistance assessed by HOMA were determined in all participants. Results: After the metformin treatment the BMI was lower in Group I and III(p--0.007 and p--0.008, respectively), the serum HDL-cholesterol levels were higher in Group I (p=0.049) compared to the pretreatment values. As to the insulin resistance it was lower in Group 1 (p=0.019) but not quite significantly different in Group III (p=0.063). There was no difference between the sistolic and diastolic blood pressure, waist-hip ratio, serum total cholesterol, triglyceride, apoprotein A1 and apoprotein B levels before and after the treatment. Conclusions: There was not a significant change in BMI and insulin resistance of the diabetic group with BMI<25kg/m 2 after the metformin treatment compared to the pretreatment values. These findings support that metformin treatment has beneficial effects on BMI, especially by improving the sensitivity of peripheral tissue to insulin and decreases the insulin resistance in type 2 diabetes and IGT.
I'267 Systemic Reaction Due to Metformine J.P. ORY, D. Debieuvre, C. Merle, C. Lebrun, F. Vitrey, D. Bourscheid. Internal Medicine, Paul Morel Hospital, Vesoul Cedex, France Metformine adverse reactions usually results of metabolic phenomena. The lactic acidosis is rare, resulting of a wrong use of the drug, by inhibition of the Cori cycle. Some digestive intolerances, frequent at the beginning of the treatment, is disturbing but remain benign. Allergic reactions due to Metformine are not available in the literature. Our case report: Mr E, 68 years old, is hospitalized to stabilize his type 2 diabetes mellitus (HbAlc: 9.4%). As renal and hepatic functions are correct, a Metformine treatment (Stagid R) is started. Five hours after the first therapeutic oral dose, the patient presented a malaise with hypotension, tachycardia, gastrointestinal complains and a generalized urticarial eruption. With corticosteroid, antihistamine and adrenaline parenteral treatment, the patient's conditions improved within half an hour and the urticarial eruption cleared two hours later. Skin prick test was performed four month later. Skin prick test with Metformine embonate remained negative but skin prick test with a component of the Stagid R capsules, the polyethylene glycol 6 000 was positive. Polyethylene glycol (as macrogol, polyoxyethylene glycol or povidone) macromolecule is included in more than 400 different drugs in France, with molecular weight ranging from 200 to 20 000 Daltons. Fortunately, anaphylactic adverse reactions to polyethylene glycol remained exceptional.
These findings support the use of M/G tablets as first-line treatment in type 2 diabetes.
I)266 The Effect of Metformin on Insulin Resistance and Serum Lipid Profiles in Abnormal Glucose Homeostasis N. G(~RSOY, Y. i1~61, ~. |mamo~lu, E. Tuncel, E. Ertark. Aims: Metformin has been shown to improve insulin sensitivity and to decrease the insulin resistance, and to have beneficial effects on lipid profiles in obese and lean patients with type 2 diabetes mellitus. The aim of this study was to evaluate the effect of metformin on insulin resistance and serum lipid profiles in patients with abnormal glucose homeostasis. Materials and Methods: We studied l0 type 2 diabetic subjects with BMI>25kg/m2(4 male, 6 female; the mean age:49.8+8.8yrs) (Group l) and 10 type 2 diabetic subjects BMI<25kg/m2(8 male, 2 female;
P268 Control of Metabolic Syndrome with Metformin in Obese Type 2 Diabetes Mellitus Patients D.A. DE LUIS, L. Cuellar, C. Terroba, R. Aller, D. Bellido, G. Piedrola, A. Becerra, A. Villar, E. Romero. Institute of Endocrinology and Nutrition; Medicine School; Hospital Rio Hortega; University of Valladolid, Valladolid, Spain Objective: Obese patients with type 2 diabetes mellitus have often bad glycaemic control. Weight gain, hyperlipidemia and hypertension acompanics insulin therapy in these patients. The aim of our study was to evaluate the effect of metformin on these parameters in obese type 2 diabetic patients treated previously with other therapies. Methods: A prospective study was designed in a Tertiary Hospital in an urban area in Spain. A population of 39 non-insulin-dependent diabetic
$52
Poster Session I
outpatients were analyzed in a prospective way. All patients were treated with metformin during three months in a step up doseage schedule. Results: A decrease in basal glucose (24.8%) (173.14-29.8 mg/dl vs 134.84-21.4 mg/dl;p<0.001) and HbAlc levels (15.4%) (8.54-1.4% vs 7.2+1.1%;p<0.001) were achieved with a decrease in the number of hypoglycaemias, dose of insulin (33.644-15.5 UI/day vs 20.574-18.4 UI/day;p<0.005) (39%) and dose of sulfonylurea (107.54-119 mg/day vs 57.54-92 mg/day;p<0.001(46%). A total of (25.6%) patients stopped the previous treatment with a good control alone with metformin (HbAlc<6,5%). Cardiovascular risk factors improved with a significant decrease in LDL levels (12.9%) (147.34-33.7 mg/dl vs 128.84-28.6 mg/dl ;p <0.05), total cholesterol levels (224.64-126.9 mg/dl vs 205.3 4-34.5 mg/dl;p<0.01) (8.5%), triglycerides levels (139.84-57 mg/dl vs 120.14-42.7 mg/dl;p<0.001) (13.7%) without changes in HDL. Blood pressure improve, with a significant decrease in systolic (137.94-27 mmHg vs 130.74-20;p<0.01) (5%) and diastolic (854-10 mmHg vs 79.34-14 mmHg;p<0.01) (9.4%) pressure. No patient dropped out the treatment due to side effects and the weight was similar during the treatment. Conclusion: In summary, the addition of metformin improved glycaemic, lipid and blood pressure control in obese diabetic type 2 patients, with a low incidence of side effects.
P269 Metabolic Responses to the Maximal Exercise Test in Patients with ~,pe 2 Diabetes Treated with Metformin.Comparision with Healthy Controls M.R. CUNHA, M.E.R. Silva, E. Watanabe, I.C. Trombeta, H.A. Machado R.T. Fukui, M.R.S. Correia, R.E Santos, B.L. Wajchenberg, D.M. Rocha, C.E. Negr~o, M.J.M. Ursich. The exercise treadmill test is usually accomplished in diabetics patients to identify silent coronary arterial disease or to determine the ideal intensity of exercise to be practiced. Objetives: The effects of the metformin during exercise treadmill test were evaluate in patients with type 2 diabetes in good glucose control (Glycated hemoglobin =7,94- 0,3%) and compared with healthy volunteers matched in age and body mass index (BMI). Materials and Methods: Six women with type 2 diabetes(M), aged 44,8 4- 5,8 years, BMI of 28,6 4-3,4 kg/m 2 and seven control volunteers(C), aged 43,6 4- 6,1 years, BMI of 28,5 4- 2,7 kg/m2, exercised on a bicycle ergometer to detemination of the maximal oxygen uptake (VO 2 max). After 30 minutes of rest and venous puncture, blood was collected for measurements of glucose, insulin, glucagon, lactate, norepinephrine and free fatty acid(FFA) levels at times -60, 0 (beginning of the exercise), end of the exercise, and after 10 and 20 minutes of the recovery phase. Thirty minutes before the exercise a standard breakfast with 300 Kcal was offered to all the participants. The diabetics patients took Metformin with the meal (500 a 850 mg). Results: The VO 2 max in the metformin group and control group were comparable: 18,54-1,2 ml/kg/min and 20,5 4- 1,8 ml/kg/min, respectively. Blood glucose levels were higher in the metformin group at fasting (125,5 4-10,4 mg/dl vs 88,14- 5,5 mg/dl) and during all the times of the test (p <0,05). The plasma glucose levels increased in the exercise and remained high during recovery only in the metformin group (p<0,01). In the control group, the insulin levels increased after the meal (9,34-2,9 $36,7 4- 14,1 /zUI/ml; p<0,001) and decreased with exercise (36,7 4- 14,1 ,1.16,8 49,9 #Ul/ml; p<0,01), but they did not change in the metformin group. The plasma FFA levels decreased with exercise in both groups (M: 0,66 4-0,2850,46 4- 0,16 mEq/l x C: 0,64 4-0,2350,394-0,05 mEq/1; p< 0,05) but they rose in the metformin group at the recovery phase (0,46 4- 0,16 $0,57 4- 0,17mEq/1; p<0,05). The fasting lactate levels did not differ among the groups; increased with exercise (M: 13,2 4-5,4546,9 4- 6,3 x C: 10,94-0,9,1.63,14-25,7 mg/dl; p<0,05) and decreased at the recovery period, but this fall was slower in the metformin group. The fasting glucagon levels were greater in metformin group (M: 83,2 4-10,9 x C:
63,6 4-10,3 pg/ml), increased after the feeding and stayed high during the exercise and recovery period. The plasma norepinephrine was comparable in two groups, increased with exercise and decreased after finishing the procedure. Conclusion: The diabetics patients treated with Metformin presented altered metabolic response at the exercise treadmill test. The plasma glucose levels were higher in the diabetic patients associated with higher glucagon levels. There was no fall in plasma insulin levels during the test. In spite of the comparable increse of lactate levels, they remained more more elevated at the recovery phase in the metformin group.
P270 Evaluation of the Response during Moderate Exercise in Patients with 1~pe 2 Diabetes Treated with Mefformin.Comparision with Healthy Controls M.R. CUNHA, M.E.R. Silva, E. Watanabe, I.C. Trombeta, H.A. Machado, R.T. Fukui, M.R.S. Correia, R.E Santos, B.L. Wajchenberg, D.M. Rocha, C.E. Negr~o, M.J.M. Ursich. The physical activity is fundamental for the control of the diabetes and in the preventing the cardiovascular complications. There are few studies evaluating the metabolic responses during prolonged physical exercise in diabetic patients treated with Metformin. ObJetives. The effects of the Metformin during physical exercise of moderate intensity (50-55% of the maximal oxygen uptake - VO2 max) in type 2 diabetics in good control (Glycated hemoglobin = 7,9 -4- 0,3%) were compared with healthy controls matched in age and body mass index (BMI). Materials and Methods: Six women with type 2 diabetes (M), aged 44,8 4- 5,8 years, BMI of 28,6 4-3,4 kg/m z and seven control volunteers (C), aged 43,6 4- 6,1 years, BMI of 28,5 4- 2,7 kg/m2, exercised in bicycle ergometer at 50 - 55% of the VO 2 max for 45 minutes. After 30 minutes of rest and venous puncture, blood was collected for determinations of glucose, insulin, glucagon, lactate, norepinephrine and free fatty acids (FFA) at the times -60, 0 (beginning of the exercise), +15, +30, +45, +60 and +90 rain. Thirty minutes before the exercise a standard breakfast with 300 Kcal was offered to all the participants. The diabetics patients took Mefformin with the meal (500 -850 mg). Results: The metformin and control groups trained at VO 2 of 9,1 ml/kg/min and at 10,3 ml/kg/min respectively (N.S). Fasting glycemia was higher in the Metformin group (134,24-32,4 mg/dl) compared with controls (82,4 4-13,6 mg/dl) and during all the procedure (p <0,05). The fasting insulin levels (M: 11,4 4-3,6 x C: 9,3 4- 4,4 #Ul/ml) was comparable in both groups. After the meal, there was a trend to increase in plasma glucose (M: 134,2 4-32,4 $149,3 4-36,4 mg/dl x C: 82,4 +13,6 $ 109,14-23,1 mg/dl) and serum insulin levels (M: 11,4 4-3,6 $23,4 -4- 18,4 #Ul/ml x C: 9,3 4- 4,4 $29,44-14/.tU1/ml), significant only in the control group. They did not change during exercise in both groups. The FFA levels decreased at time +30, significant only in the healthy volunteers (p<0,05). The fasting lactate levels did not differ among the groups (M: 18,2 4-7,8 mg/dl x C: 10,8 4-4,0 mg/dl); increased with exercise in the diabetic patients and controls (p<0,05), but it remained high in the metformin group up to the end of the recovery. The glucagon plasma levels were similar in both groups and they did not change with exercise. The norepinephrine response was the same among the studied groups. Condusion: The Metformin is a safe drug during exercise in diabetics patients with good control, because it does no cause hipoglycemia. However the lactate levels remained high even after 45 minutes of the end of the physical exercise.
P265 Metformin/Glyburide Tablets as First-Line Treatment in Type 2 Diabetes: Distribution of HbA~ Response JAIME A. DAVIDSON l, Alan Garber 2, Arshag D. Mooradian 3, Stephen Schneider 4, David Henry z. 1 Endocrine & Diabetes Association of Texas, Dallas, TX, United States of America; 2 Pharmaceutical Research Institute, Bristol-Myers Squibb, Princeton, NJ, United States of America; 3Division of Endocrinology, St Louis University School of Medicine, St Louis, MI, United States of America; 4 Robert Wood Johnson Medical School, Piscataway, NJ, United States of America The pathogenesis of type 2 diabetes involves both impaired insulin secretion and increased insulin resistance. Use of two oral antidiabetic agents with complementary mechanisms of action may result in a greater response than either drug alone. This multicenter study evaluated the efficacy of two metformin/glyburide (M/G) tablet dosages after 20 weeks of oral administration as first-line therapy. Patients (n=806) were randomly assigned to receive placebo, glyburide (2.5 mg), metformin (500 mg), or M/G tablets (250 mg/1.25 mg or 500 mg/2.5 mg). Doses were titrated over an 8-week period based on glycemic response. A greater percentage of patients in the M/G 250 mg/l.25 mg (66%) and M/G 500 mg/2.5 mg (72%) treatment groups achieved hemoglobin Arc levels of less than or equal to 7% compared with placebo (20%), glyburide (60%), and metformin (50%) at Week 20. HbAic%
Absolute <7.0 7.1-7.9 >8.0 Decrease <0.5 0.5-0.9 1.0-1.4 1.4-1.9 >2.0
Placebo n=147 n(%)
Gly 2.5 mg n=142 n(%)
Met500mg n=141 n(%)
M/G 25~1.25 n=149 n(%)
M/G 5(}0/2.5 n=152 n(%)
29 (20) 55 (37) 63 (43)
85 (60) 37 (26) 20 (14)
71 (50) 42 (30) 28 (20)
99 (66) 38 (26) 12 (8)
109 (72) 29 (19) 14 (9)
98 (67) 24 (16) 15 (10) 5 (3) 5 (3)
28 (20) 32 (23) 28 (20) 30 (21) 24 (17)
39 (27) 35 (25) 26 (18) 20 (14) 22 (16)
28 (19) 23 (15)
21 (14) 24 (16) 32 (21) 32 (21) 43 (28)
26 (17) 42 (28)
$51
the mean age:49.8+9.1 yrs) (Group II) and 10 subjects BMI>25kg/m 2 with impaired glucose tolerance (IGT) (4 male, 6 female; the mean age:41.3-4-11.1yrs) (Group III) to determine the effect of 12 weeks of treatment with metformin 2.5g/day on insulin resistance and lipid profiles. Before and after treatment sistolic and diastolic blood pressure, waist-hip ratio, serum total cholesterol, HDL-cholesterol, triglyceride, apoprotein A1, apoprotein B and the insulin resistance assessed by HOMA were determined in all participants. Results: After the metformin treatment the BMI was lower in Group I and III(p--0.007 and p--0.008, respectively), the serum HDL-cholesterol levels were higher in Group I (p=0.049) compared to the pretreatment values. As to the insulin resistance it was lower in Group 1 (p=0.019) but not quite significantly different in Group III (p=0.063). There was no difference between the sistolic and diastolic blood pressure, waist-hip ratio, serum total cholesterol, triglyceride, apoprotein A1 and apoprotein B levels before and after the treatment. Conclusions: There was not a significant change in BMI and insulin resistance of the diabetic group with BMI<25kg/m 2 after the metformin treatment compared to the pretreatment values. These findings support that metformin treatment has beneficial effects on BMI, especially by improving the sensitivity of peripheral tissue to insulin and decreases the insulin resistance in type 2 diabetes and IGT.
I'267 Systemic Reaction Due to Metformine J.P. ORY, D. Debieuvre, C. Merle, C. Lebrun, F. Vitrey, D. Bourscheid. Internal Medicine, Paul Morel Hospital, Vesoul Cedex, France Metformine adverse reactions usually results of metabolic phenomena. The lactic acidosis is rare, resulting of a wrong use of the drug, by inhibition of the Cori cycle. Some digestive intolerances, frequent at the beginning of the treatment, is disturbing but remain benign. Allergic reactions due to Metformine are not available in the literature. Our case report: Mr E, 68 years old, is hospitalized to stabilize his type 2 diabetes mellitus (HbAlc: 9.4%). As renal and hepatic functions are correct, a Metformine treatment (Stagid R) is started. Five hours after the first therapeutic oral dose, the patient presented a malaise with hypotension, tachycardia, gastrointestinal complains and a generalized urticarial eruption. With corticosteroid, antihistamine and adrenaline parenteral treatment, the patient's conditions improved within half an hour and the urticarial eruption cleared two hours later. Skin prick test was performed four month later. Skin prick test with Metformine embonate remained negative but skin prick test with a component of the Stagid R capsules, the polyethylene glycol 6 000 was positive. Polyethylene glycol (as macrogol, polyoxyethylene glycol or povidone) macromolecule is included in more than 400 different drugs in France, with molecular weight ranging from 200 to 20 000 Daltons. Fortunately, anaphylactic adverse reactions to polyethylene glycol remained exceptional.
These findings support the use of M/G tablets as first-line treatment in type 2 diabetes.
I)266 The Effect of Metformin on Insulin Resistance and Serum Lipid Profiles in Abnormal Glucose Homeostasis N. G(~RSOY, Y. i1~61, ~. |mamo~lu, E. Tuncel, E. Ertark. Aims: Metformin has been shown to improve insulin sensitivity and to decrease the insulin resistance, and to have beneficial effects on lipid profiles in obese and lean patients with type 2 diabetes mellitus. The aim of this study was to evaluate the effect of metformin on insulin resistance and serum lipid profiles in patients with abnormal glucose homeostasis. Materials and Methods: We studied l0 type 2 diabetic subjects with BMI>25kg/m2(4 male, 6 female; the mean age:49.8+8.8yrs) (Group l) and 10 type 2 diabetic subjects BMI<25kg/m2(8 male, 2 female;
P268 Control of Metabolic Syndrome with Metformin in Obese Type 2 Diabetes Mellitus Patients D.A. DE LUIS, L. Cuellar, C. Terroba, R. Aller, D. Bellido, G. Piedrola, A. Becerra, A. Villar, E. Romero. Institute of Endocrinology and Nutrition; Medicine School; Hospital Rio Hortega; University of Valladolid, Valladolid, Spain Objective: Obese patients with type 2 diabetes mellitus have often bad glycaemic control. Weight gain, hyperlipidemia and hypertension acompanics insulin therapy in these patients. The aim of our study was to evaluate the effect of metformin on these parameters in obese type 2 diabetic patients treated previously with other therapies. Methods: A prospective study was designed in a Tertiary Hospital in an urban area in Spain. A population of 39 non-insulin-dependent diabetic
$52
Poster Session I
outpatients were analyzed in a prospective way. All patients were treated with metformin during three months in a step up doseage schedule. Results: A decrease in basal glucose (24.8%) (173.14-29.8 mg/dl vs 134.84-21.4 mg/dl;p<0.001) and HbAlc levels (15.4%) (8.54-1.4% vs 7.2+1.1%;p<0.001) were achieved with a decrease in the number of hypoglycaemias, dose of insulin (33.644-15.5 UI/day vs 20.574-18.4 UI/day;p<0.005) (39%) and dose of sulfonylurea (107.54-119 mg/day vs 57.54-92 mg/day;p<0.001(46%). A total of (25.6%) patients stopped the previous treatment with a good control alone with metformin (HbAlc<6,5%). Cardiovascular risk factors improved with a significant decrease in LDL levels (12.9%) (147.34-33.7 mg/dl vs 128.84-28.6 mg/dl ;p <0.05), total cholesterol levels (224.64-126.9 mg/dl vs 205.3 4-34.5 mg/dl;p<0.01) (8.5%), triglycerides levels (139.84-57 mg/dl vs 120.14-42.7 mg/dl;p<0.001) (13.7%) without changes in HDL. Blood pressure improve, with a significant decrease in systolic (137.94-27 mmHg vs 130.74-20;p<0.01) (5%) and diastolic (854-10 mmHg vs 79.34-14 mmHg;p<0.01) (9.4%) pressure. No patient dropped out the treatment due to side effects and the weight was similar during the treatment. Conclusion: In summary, the addition of metformin improved glycaemic, lipid and blood pressure control in obese diabetic type 2 patients, with a low incidence of side effects.
P269 Metabolic Responses to the Maximal Exercise Test in Patients with ~,pe 2 Diabetes Treated with Metformin.Comparision with Healthy Controls M.R. CUNHA, M.E.R. Silva, E. Watanabe, I.C. Trombeta, H.A. Machado R.T. Fukui, M.R.S. Correia, R.E Santos, B.L. Wajchenberg, D.M. Rocha, C.E. Negr~o, M.J.M. Ursich. The exercise treadmill test is usually accomplished in diabetics patients to identify silent coronary arterial disease or to determine the ideal intensity of exercise to be practiced. Objetives: The effects of the metformin during exercise treadmill test were evaluate in patients with type 2 diabetes in good glucose control (Glycated hemoglobin =7,94- 0,3%) and compared with healthy volunteers matched in age and body mass index (BMI). Materials and Methods: Six women with type 2 diabetes(M), aged 44,8 4- 5,8 years, BMI of 28,6 4-3,4 kg/m 2 and seven control volunteers(C), aged 43,6 4- 6,1 years, BMI of 28,5 4- 2,7 kg/m2, exercised on a bicycle ergometer to detemination of the maximal oxygen uptake (VO 2 max). After 30 minutes of rest and venous puncture, blood was collected for measurements of glucose, insulin, glucagon, lactate, norepinephrine and free fatty acid(FFA) levels at times -60, 0 (beginning of the exercise), end of the exercise, and after 10 and 20 minutes of the recovery phase. Thirty minutes before the exercise a standard breakfast with 300 Kcal was offered to all the participants. The diabetics patients took Metformin with the meal (500 a 850 mg). Results: The VO 2 max in the metformin group and control group were comparable: 18,54-1,2 ml/kg/min and 20,5 4- 1,8 ml/kg/min, respectively. Blood glucose levels were higher in the metformin group at fasting (125,5 4-10,4 mg/dl vs 88,14- 5,5 mg/dl) and during all the times of the test (p <0,05). The plasma glucose levels increased in the exercise and remained high during recovery only in the metformin group (p<0,01). In the control group, the insulin levels increased after the meal (9,34-2,9 $36,7 4- 14,1 /zUI/ml; p<0,001) and decreased with exercise (36,7 4- 14,1 ,1.16,8 49,9 #Ul/ml; p<0,01), but they did not change in the metformin group. The plasma FFA levels decreased with exercise in both groups (M: 0,66 4-0,2850,46 4- 0,16 mEq/l x C: 0,64 4-0,2350,394-0,05 mEq/1; p< 0,05) but they rose in the metformin group at the recovery phase (0,46 4- 0,16 $0,57 4- 0,17mEq/1; p<0,05). The fasting lactate levels did not differ among the groups; increased with exercise (M: 13,2 4-5,4546,9 4- 6,3 x C: 10,94-0,9,1.63,14-25,7 mg/dl; p<0,05) and decreased at the recovery period, but this fall was slower in the metformin group. The fasting glucagon levels were greater in metformin group (M: 83,2 4-10,9 x C:
63,6 4-10,3 pg/ml), increased after the feeding and stayed high during the exercise and recovery period. The plasma norepinephrine was comparable in two groups, increased with exercise and decreased after finishing the procedure. Conclusion: The diabetics patients treated with Metformin presented altered metabolic response at the exercise treadmill test. The plasma glucose levels were higher in the diabetic patients associated with higher glucagon levels. There was no fall in plasma insulin levels during the test. In spite of the comparable increse of lactate levels, they remained more more elevated at the recovery phase in the metformin group.
P270 Evaluation of the Response during Moderate Exercise in Patients with 1~pe 2 Diabetes Treated with Mefformin.Comparision with Healthy Controls M.R. CUNHA, M.E.R. Silva, E. Watanabe, I.C. Trombeta, H.A. Machado, R.T. Fukui, M.R.S. Correia, R.E Santos, B.L. Wajchenberg, D.M. Rocha, C.E. Negr~o, M.J.M. Ursich. The physical activity is fundamental for the control of the diabetes and in the preventing the cardiovascular complications. There are few studies evaluating the metabolic responses during prolonged physical exercise in diabetic patients treated with Metformin. ObJetives. The effects of the Metformin during physical exercise of moderate intensity (50-55% of the maximal oxygen uptake - VO2 max) in type 2 diabetics in good control (Glycated hemoglobin = 7,9 -4- 0,3%) were compared with healthy controls matched in age and body mass index (BMI). Materials and Methods: Six women with type 2 diabetes (M), aged 44,8 4- 5,8 years, BMI of 28,6 4-3,4 kg/m z and seven control volunteers (C), aged 43,6 4- 6,1 years, BMI of 28,5 4- 2,7 kg/m2, exercised in bicycle ergometer at 50 - 55% of the VO 2 max for 45 minutes. After 30 minutes of rest and venous puncture, blood was collected for determinations of glucose, insulin, glucagon, lactate, norepinephrine and free fatty acids (FFA) at the times -60, 0 (beginning of the exercise), +15, +30, +45, +60 and +90 rain. Thirty minutes before the exercise a standard breakfast with 300 Kcal was offered to all the participants. The diabetics patients took Mefformin with the meal (500 -850 mg). Results: The metformin and control groups trained at VO 2 of 9,1 ml/kg/min and at 10,3 ml/kg/min respectively (N.S). Fasting glycemia was higher in the Metformin group (134,24-32,4 mg/dl) compared with controls (82,4 4-13,6 mg/dl) and during all the procedure (p <0,05). The fasting insulin levels (M: 11,4 4-3,6 x C: 9,3 4- 4,4 #Ul/ml) was comparable in both groups. After the meal, there was a trend to increase in plasma glucose (M: 134,2 4-32,4 $149,3 4-36,4 mg/dl x C: 82,4 +13,6 $ 109,14-23,1 mg/dl) and serum insulin levels (M: 11,4 4-3,6 $23,4 -4- 18,4 #Ul/ml x C: 9,3 4- 4,4 $29,44-14/.tU1/ml), significant only in the control group. They did not change during exercise in both groups. The FFA levels decreased at time +30, significant only in the healthy volunteers (p<0,05). The fasting lactate levels did not differ among the groups (M: 18,2 4-7,8 mg/dl x C: 10,8 4-4,0 mg/dl); increased with exercise in the diabetic patients and controls (p<0,05), but it remained high in the metformin group up to the end of the recovery. The glucagon plasma levels were similar in both groups and they did not change with exercise. The norepinephrine response was the same among the studied groups. Condusion: The Metformin is a safe drug during exercise in diabetics patients with good control, because it does no cause hipoglycemia. However the lactate levels remained high even after 45 minutes of the end of the physical exercise.