2006 diabetes vietnam compressed 12+

Fatty liver Liver Insulin resistance increased glucose output Fat Poisoning Fat Poisoning Fat + Inactivity Fatty muscles Muscle Insulin resistance Fat Poisoning Fat Poisoning Fat Poisoning Fat Poisoning Beta cell failure Inadequate insulin To counter Insulin resistance Hyperglycaemia Sugar Poisoning Sugar Poisoning Beta-cell failure • Ectopic deposition of fat in the islet cells leads to Beta-cell failure Burned-out Pancreas INSULIN RESISTANCE TIME 11 5 7.1 Plasma Glucose Impaired glucose tolerance Ausdiab 10.6 % population 1.3 million Australians NIDDM FPG >7; 2hr >11 INSULIN Beta cell failure Insulin resistance combined with beta-cell dysfunction 6.1 Treat B-cell failure & Insulin resistance Multi-target treatment Multi-target treatment Central obesity Vascular-thrombotic Complications β-Cell Preservation Insulin Resistance Micro-vascular Complications Insulin Secretion + INSULIN + INSULIN +/or Glitazones DIET+ EXERCISE DIET+ EXERCISE Management of Diabetes Twice Daily Twice Daily Sulphonylurea Sulphonylurea Metformin Metformin + WT loss Drugs + WT loss Drugs Reductil Acomplia Once Daily Once Daily Sulphonylurea Sulphonylurea Amaryl 0 0.5 1 1.5 2 2.5 3 100 10 1 0 2.5 5 10 20 Glimepiride Concentration ( µ mol/L) Glucose (mmol/L) Insulin secretion* ( µ U/islet/45min) Del Guerra et al. Acta Diabetol 2000;37:139. *Isolated human pancreatic islets Amaryl: Physiologic Insulin Secretion Dependent on Glucose Concentration Responsiveness of Sulfonylureas to Changing Glucose Concentrations Insulin secretion (% of cell content) Design: • Incubation of human islets for 24 h with different sulfonylureas • Glucose stimulus for 45min 3.3mM glucose (dark shade) and 16.7mM (light shade) * P < .01 † P < .05 * Del Guerra et al. submitted to EASD 2001. ns Gp = Glimepiride; Gb = glibenclamide; Chl = Chlorpropamide 0 1 2 3 4 5 6 Control Gp 10?M Gb 10?M Chl 600?M [...]... obesity Macro-vascular •Lipids •Thrombosis •Inflammation Value of weight loss • Risk of type 2 diabetes greatly reduced by substantive weight loss • Weight loss can achieve reversion to normal glucose tolerance • Diabetes Prevention Program showed lifestyle intervention (diet + exercise) reduced the incidence of diabetes by 58% (vs controls) Reward system • Endocannabinoid system involved in incentive... combination + basal insulin uptitration HbA1c (%) 10 9 8 7 6 Duration of diabetes OAD + multiple daily insulin injections Proactive management of glycaemia: early combination approach Diet OAD monotherapy 10 OAD combinations HbA1c (%) OADs uptitration 9 OAD + basal insulin OAD + multiple daily insulin injections 8 7 6 Duration of diabetes Steno 2 trial • 8 yr study of 160 diabetics + microalbuminuria... insulin sensitivity …ineglucos tolerant, insulin -resistant offspring of patients with type 2 diabetes. ” Volk et al.Diabetologia 2000;43(suppl 1):A39 Glycaemic goals • • • • Fasting plasma glucose . Complications Insulin Secretion + INSULIN + INSULIN +/or Glitazones DIET+ EXERCISE DIET+ EXERCISE Management of Diabetes Twice Daily Twice Daily Sulphonylurea Sulphonylurea Metformin Metformin + WT loss Drugs +. Day With Once-Daily Glimepiride Amaryl 8am 12 noon 6pm 10pm 2 am 24 Hours Patients with type 2 diabetes 0.43 episodes/1000 person-years vs 5.8 episodes/1000 person- years glimepiride fewer. Glipizide Glimepiride Phase III clinical data showed a trend toward weight neutrality Bugos et al. Diabetes Res Clin Pract 2000;50 (suppl 1). *Meta-analysis of data from 4 studies Mean Change in