How to Prevent Progressivity of Type 2 Diabetes, Insulin Resistance and Prediabetes : Clinical Consequences and Therapy

How to Prevent the Progressivity of Type 2 Diabetes, Insulin Resistance and Prediabetes : Clinical Consequences and TherapySlamet SuyonoDiabetes and Lipid Center University of IndonesiaJakartaUNS Solo 8 Sept 20071SlametS2Scope of the talkPrevention of the Progressivity of Type 2 DiabetesPrevention of the Progression of Insulin ResistancePrevention of the Progression of Prediabetes to Type 2 Diabetes

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0UKPDS :Natural Progressive Deterioration of b-Cell FunctionYears from DiagnosisLebovitz H. Diabetes Review 1999;7:139-53Beta Cell Function (%)-12 10 -6 -2 0 2 6 10 14 Th/ExpectationFacts4Current Treatment is UnsatisfactoryCurrent Treatments do not address the pathophysiologic defect of Type 2 DM : Insulin resistance and Insulin secretionAdapted from Type 2 Diabetes BASICS. International Diabetes Center; 2000.Pancreatic Islet Function Deteriorates over Time, Causing Disease ProgressionDiagnosisInsulinGlucosePrediabetes(IFG/IGT)NGTDiabetes Macrovascular changes Microvascular changes Inadequate-cell functionPostprandial glucoseFasting glucoseInsulin resistanceInsulin secretionProgressive Decreaseof -cell function Why ?5In healthy individuals, plasma insulin levels increase in response to any increase in demand (eg, insulin resistance caused by obesity) and euglycemia is maintained. Early in the progression to type 2 diabetes (T2DM) plasma insulin levels also increase, but this -cell compensation is inadequate, allowing at first mild fasting (impaired fasting glucose) or postprandial (Impaired Glucose Tolerance) hyperglycemia.Thus, insulin secretion (shown in the middle graph in lavender) must always be considered in the context of the prevailing degree of insulin resistance (shown in yellow).In many (but certainly not all) individuals with prediabetes, -cell function continues to decline and diabetes may be diagnosed. Both structural (decreased -cell mass) and functional (impaired glucose-sensing) abnormalities underlie the progressive decline in apparent -cell function and progressive hyperglycemia in T2DM.1 Complications, including macrovascular changes (usually associated with components of the metabolic syndrome in addition to hyperglycemia) and microvascular changes, more closely related to glucose levels per se, begin well in advance of overt diabetes, as Normal Glucose Tolerance gives way to prediabetes and then to T2DM.

ReferenceRickheim P, Flader J, Carstensen AK. Type 2 Diabetes BASICS. 2nd ed. Minneapolis, Minn: International Diabetes Center; 2000.-Cell Volume Is Significantly Decreased in Obese IFG and T2DM PatientsIFG = impaired fasting glucose; NGT = normal glucose tolerance;; T2DM = type 2 diabetes mellitus*P 9%) at baseline.

Garber A, Sankoh S, Mohideen P, Bruce S. Glyburide/metformin tablets versus metformin plus rosiglitazone in type 2 diabetes patients uncontrolled by metformin: attaining glycaemic goals. Diabetes 2003;52 (Suppl. 1):A119.

Improved Compliance Following Switch to Combination TabletsData from a retrospective analysisMelikian et al, Clin Ther 2002;24:460-7Adherence rate (%)Met + glibco-admin7187406080100p