Track 2. Clinical Research & Care S109 P462 Glucose Production during Fasting in Malaria and Healthy Subjects; The Potential Regulatory Role of Glycogenolysis FLEUR SPRANGERS 1, Huynh Van Thien l, Johannes A. Romijn 2, Mari~tte T. Ackermans 1, Hans P. Sauerwein i. 1 Department of Endocrinology and Metabolism, Academic Medical Centre, Amsterdam, Netherlands; 2Department of Internal Medicine, Leiden University Medical Centre, Leiden, Netherlands In the fed state, glycogen turnover is higher than in the fasted state, sug- gesting that glycogen content may regulate its own rate of breakdown to prevent glycogen accumulation. Whether during fasting glycogen turnover is lower to spare glycogen content is unknown. After 16 hrs fasting, non- severe Plasmodium falciparum malaria patients have a considerably lower glycogenolysis rates than healthy subjects (0.4 vs. 1.0 mg/kg/min), whereas glucose production is 25% higher (3 vs. 2.4 mg/kg/min). Purpose: If this lower glycogenolysis rate reflects a lower glycogen content, we would expect glucose production to decrease faster in malaria patients than in healthy subjects between 16 and 21 hrs of fasting, in order to restrain glycogenolysis. Methods: Malaria patients were studied on the day after admission and were treated with an artemisinine-derivate. Glucose production was measured with [6,6-2H2]-glucose infusion and gluconeogenesis with 2H20 ingestion. Results: Glucose production was 34% higher in malaria patients than in healthy volunteers after 16 hrs fast- ing (p< 0.001). Between 16 and 21 hrs of fasting: the decrease in glucose production represented a decrease in glycogenolysis as gluconeogenesis was constant; the decrease was 0.4 mg/kg/min in both malaria patients and in healthy subjects (resp. from 3.054-0.08 to 2.664-0.11 mg/kg/min (p=0.002) and from 2.274-0.12 to 1.874-0.13 mg/kg/min (p=0.00l)); glu- cose concentration was not different (resp. from 5.424-0.15 to 5.194-0.17 (n.s.) and from 5.094-0.12 to 4.854-0.11 mmol/1 (n.s.)); glucoregulatory hormones were not different but norepinephrine was lower in the malaria patients (0.584-0.09 vs. 0.94-0.13 nmol/1 ((p= 0.03)). Conclusion: During fasting, unlike in the fed state, glycogenolysis seems not to be preferentially dictated by glycogen content but driven by the necessity to maintain euglycaemia. P463 Frequency and Severity of Insulin Resistance in Type 2 Diabetes SABINE FISCHER, Carsta Koehler, Wolfgang Metzler, Markolf Hanefeld. Insulin resistance (IR) is an important pathogenetic mechanism which contributes to the glucose intolerance of type 2 diabetes. But the extent of IR varies in a wide range in type 2 diabetics. Up to now only scare information exists on frequency and severity of IR in unselected type 2 diabetes. We investigated in a representative group of consecutive type 2 diabetic patients the prevalence and the degree of IR in comparison to healthly controls. Material and methods: Ninety six type 2 diabetic patients (mean (SD): age 58.9 (6.2) years, BM127.4 (3.5) kg/m2, WHR 0.97 (0.07)) and 18 controls (age 53.9 (7.1) years, BMI 26.8 (5.1) kg/m2, WHR 0.87 (0.08)) we included. All probands were examined by euglycemic hyperinsulinemic clamp according to De Fronzo. The antidiabetic drug therapy of the diabetic patients was interrupted at the least 4 weeks before the beginning of the study. Basal blood glucose and insulin, triglycerides, total, HDL- and LDL-cholesterol and free fatty acids were measured. Results: We found a significant difference (p <0.001) in insulin sensitivity (Me) between diabetic patients (Mc 2.24 (1.18) mg (kg body weight • min • insulin)-I and controls (Mc 5.59 (2.40) mg (kg body weight • min • insulin)-l). The 25th and 75th percentile of the Mc (3.18... 7.03 mg (kg body weight • rain • insulin)-l) value was calculated in the control group. The 25th percentile was regarded as the upper normal range of Mc. Following the diabetic patients were separated in 2 groups: Mc < 3.18 resp. Mc 3 3.18. According to this cut-off limit 26% of the diabetic patients had no insulin resistance. This group shown significantly higher HDL-cholesterol values (1.22 vs. 0.93 mmol/l; p--0.002), significantly lower insulin (23.9 vs. 36.2/zmol/1; p<0.001) and triglyceride 1.72 vs. 2.45 mmol/l; p---0.009) concentrations as the diabetic group with Mc < 3.18. No differences were found in BMI (26.9 vs. 27.6 kg/m2), WHR (0.96 vs.0.98), duration of diabetes (72.7 vs. 75.7 mounths), basal blood glucose (9.8 vs. 10.5 mmol/l) and LDL-cholesterol (3.72 vs. 3.78 mmol/l) between the two diabetic groups. In conclusion our results have shown that only 74% of the investigated type 2 diabetic patients exhibited IR. In 26% of the cases we found no insulin resistance (Me>3.18) in the diabetic study group. Our data indicate that type 2 diabetes is not simply synonymousfor insulin resistance. P464 Non-Pharmacological Primary Prevention of Type 2 Diabetes. Impaired Glucose Tolerance Conversion Rate in Spain BERNARDO COSTA, Angel Donado, Francisco Martin, M.Teresa Basora, J.Luis Pifiol. IGT Research Group; Reus-Altebrat Division, Catalan Health Institute, Reus, Tarragona, Spain To prospectively evaluate the progression to diabetes and regression to normal tolerance in a high-risk Spanish population with impaired glucose tolerance (IGT). From 1995 untill 1998 an IGT cohort was screened among subjects with at least one major risk factor for diabetes (obesity, a first-degree relative with diabetes, hyperglycaemic agents or previous unclassified glucose abnormalities). This study involved 10 primary health care centers (230,000 inhabitants) in Catalonia. During the follow-up period subjects underwent an individually designed educational programme on dietetics and cardiovascular health as well as an annual standardized oral glucose tolerance test to measure fasting (FPG) and 2h plasma glucose (2hPG). In January-2000, index and probability of diagnostic variation (Kaplan-Meier and Cox proportional hazards model; OR=Odds Ratio) were assessed. Among 580 screened subjects, 157 (27.1%) fullfilled the criteria of IGT (95%CI=23.5-30.7%) and 132 of them were evaluated: 57 male (43.2%), 61-4-11 y., 31.14-5 kg.m-2, 57 (43.2%) with one risk factor and 75 (56.8%) with two or more risk factors. The mean follow-up time was 25.4 months and the cumulative diagnostic incidence was: 33 (25%) normal glucose tolerance, 54 (40.9%) IGT and 45 (34.1%) diabetes. The corresponding annual rates were: 11.8% (regression index), 19.3% (persistent IGT) and 16.1% (progression index). The risk of persistent IGT up to 3 y. was 43.4% (33.5-53.3%) and the probability of reversion was 39.9% (27.2-52.6%). The two-year risk for developing diabetes was 22.3% (13.4-31.1%) suffering a dramatic increase during the third year: 68% (56-80%). Only previous glucose abnormality independently predicted diabetes progression [OR=1.43 (1.03-1.97); p<0.03] and 2hPG, not FPG, regression to normality [OR=0.57 (0.37-0.86); p<0.008)]. IGT conversion rate to diabetes is elevated on high-risk Spanish pop- ulation, increasing up to the second year despite non-pharmacological intervention. 2hPG would be able to select an IGT subpopulation subsidiary of a more agressive preventive measures (pharmacological intervention). P465 Effects of Smoking on Insulin Sensitivity, Insulin Clearance, and Time-Action Profile Following Regular Human Insulin STEPHAN D. WISE 1, Eng Seng Seah 1, Moriyoshi Yasuda l, Jeannine Fisher 2, Korbtham Sathirakul I, Paul R. Aftring 2. t Lilly-Nus Centrefor Clinical Pharmacology, National University of Singapore, Singapore; 2Eli Lilly and Company, Indianapolis, IN, UnitedStates of America Previous studies have shown relative insulin resistance in a smoking population. This has been ascribed to vascular changes impacting muscle.