Presentation on theme: "Diabetes Mellitus and Metabolic Syndrome"— Presentation transcript:
1 Diabetes Mellitus and Metabolic Syndrome By: Susan Yu-Gan, MD, FPCP
2 Definitionrefers to a group of common metabolic disorders that share the phenotype of hyperglycemia.Defect in metabolism of carbohydrates, fats and proteins due to relative/absolute deficiency in insulin secretion or actionResult in severe complications
4 DM Local Prevalence Rate Population = 80 MDM Prevalence:*FBS : 3.4 %** FBS : 6.6 %FBS/history : 4.6 %Filipino DM : M*FBS > 125 mg/dL **FBS ≥101 mg/dLMorales D et al. for the NNHeS Group. PSH-PLS Convention. Feb 2005.Sy R et al. PJIM. 2003; 41: 1.-6.
5 Numbers Of People With Diabetes: Regional Figures For 2007 And Estimates For 2025 AFR, Africa; EMM, Eastern Mediterranean; EUR, Europe; NA, North America;SAC, South and Central America; SEA, South -East Asia; WP, Western PacificInternational Diabetes Federation. Diabetes Atlas, 3rd edn. Brussels: IDF, 2006.5
6 The Epidemic of Type 2Rise in the prevalence and incidence of type 2 diabetes . Why?Increased awareness, more diagnosedNew ADA and WHO criteriaLonger life spanObesityGeographic variationsPotential huge economic burden - complications
8 Unique Features Of The Diabetes Epidemic In Asia The increase in type 2 diabetes in Asia developed:in a shorter timein a younger age groupin people with a much lower BMIin people with a high predisposition to insulin resistance at a lesser degree of obesity than people of European descentAsian Indians are more prone to diabetes because of increased insulin resistance, greater abdominal adiposity (i.e. higher waist circumference despite lower body mass index), lower adiponectin and higher high sensitive C-reactive protein levels. The primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity.Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2 diabetes: Indian scenario. Indian J Med Res 2007; 125: 217–30.Yoon KH et al. Lancet 2006; 368: 1681–8.8
9 Risk Factors for Type 2 Diabetes Patient CharacteristicsMedical HistoryClinical FindingsAge > 45 years oldFamily historyHypertensionOverweight/Obesity (BMI > 25 kg/m2)Coronary artery diseaseDyslipidemiaPhysical inactivityCerebrovascular accidentsRace-AsiansPrevious history of IFG/IGT/GDMDiscuss each oneADA. Screening for Type 2 Diabetes. Diabetes Care 2003; 26(Suppl1):s21-s24
10 Screening Recommendations Mass screening for type 2 diabetes in the general population is not recommended (Grade D, consensus)Testing for diabetes should be performed every 3 years in those over 45 years of age (Grade D, consensus)What’s grade D?Define FPGThe Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26 (Suppl 1) S5-20
11 Who Should Be Screened?All adults 45 y/o; and, if normal, at 3-yr intervalsYounger age and more frequently in those at riskObeseFirst degree relative with diabetesHigh risk ethnic groupHx of GDM or delivered baby > 9 lbs.Hypertension (BP140/90)Dyslipidemia (HDL 35 mg/dL and/or triglyceride 250 mg/dLPrevious IFG or IGTADA. Diabetes Care 2000: 23 (suppl 1);
12 Confirming the Diagnosis of Type 2 Diabetes mellitus Only possible through serum glucose measurement
13 Methods for Diagnosing DM FPG 126 mg/dL (after 8 hr fast)Random Plasma Glucose 200 mg/dL w/ classic diabetes symptomsPolyuria, polydipsia, unexplained wt lossOGTT value 200 mg/dL in the 2-h sampleConfirmed on at least 2 occasionsA1c not routine test for diagnosis (2006)ADA. Diabetes Care 2000:23(suppl.1);
14 Pre-Diabetes (IFG and IGT) Levels of GlycemiaNormalPre-Diabetes (IFG and IGT)Diabetes MellitusFPG<100 mg/dL (5.6 mmol/L)mg/dL ( mmol/L)> 126 mg/dL (7.0 mmol/L)2hPG< 140 mg/dL (7.8 mmol/L)mg/dL ( mmol/L)> 200 mg/dL (11.1 mmol/L)What does casual plasma glucose mean?Define all acronyms
15 Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG) IGT and IFG refer to a metabolic stage intermediate between normal glucose homeostasis and diabetesIGT: 2hPG mg/dL to 199 mg/dLIFG: FBG mg/dL to 125 mg/dLBoth are risk factors for future diabetes and cardiovascular diseaseRearrange slides .. the order doesn’t make sense to me…ADA. Standards of medical care in diabetes. Diabetes Care 2004; 27 (Suppl 1):S13-34
16 Etiologic Classification of Diabetes Mellitus Type 1 DiabetesType 2 DiabetesOther specific typesGestational Diabetes MellitusPut in beginning
17 Type 1 DiabetesResults from autoimmune destruction of pancreatic beta-cellsAbsolute insulin deficiencyPatients typically dependent on insulin for survivalPatients may present with ketoacidosis as initial sign of the disorderKetoacidosis statement is misleadingReport of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26(Suppl 1):s5-s20
18 Type 2 Diabetes Insulin resistance and relative insulin deficiency Patients may or may not need insulin treatment to surviveMay remain undiagnosed for many years, as hyperglycemia develops slowlyAssociated with strong genetic predispositionHeterogenousKetoacidosis statement is misleadingReport of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26(Suppl 1):s5-s20
19 Other Specific Types Genetic defects of B cell function Genetic defects in insulin actionDiseases of the exocrine pancreasEndocrinopathiesDrug - or chemical - inducedInfectionsUncommon forms of immune-mediated diabetesOther genetic syndromes sometimes associated with diabetesReport of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26(Suppl 1):s5-s20
20 Gestational Diabetes Mellitus (GDM) Any degree of glucose intolerance with onset or first recognition during pregnancyAssociated with increased perinatal morbidity and mortality6 weeks or more after pregnancy ends, the woman should be reclassifiedHigh risk for type 2 DM.Put in beginningReport of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26(Suppl 1):s5-s20
21 Diagnosis of GDM with a 100-g or 75-g Glucose Load mg/dLmmol/L100-g Glucose LoadFasting955.31 - h18010.02 - h1558.63 - h1407.875-g Glucose LoadReport of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2003; 26(Suppl 1):s5-s20
23 PANCREASThe pancreas is an elongated organ nestled next to the first part of the small intestine. The endocrine pancreas refers to those cells within the pancreas that synthesize and secrete hormones.The endocrine portion of the pancreas takes the form of many small clusters of cells called islets of Langerhans or, more simply, islets. Humans have roughly one million islets.
24 PANCREASPancreatic islets house three major cell types, each of which produces a different endocrine product:Alpha Cells (A cells)secrete the hormone glucagon.Beta Cells (B cells)produce insulin and are the most abundant of the islet cells.Delta Cells (D cells)secrete the hormone somatostatin which is also produced by a number of other endocrine cells in the body.
25 PANCREASInterestingly, the different cell types within an islet are not randomly distributed - beta cells occupy the central portion of the islet and are surrounded by a "ring" of alpha and delta cells. Aside from the insulin, glucagon and somatostatin, a number of other "minor" hormones have been identified as products of pancreatic islets cells.
26 Insulin Structure of Insulin Insulin is a rather small protein, with a molecular weight of about 6000 Daltons.It is composed of two amino acid chains held together by disulfide bonds. When this two amino acid chains are split apart, the functional activity of insulin is lost.The amino acid sequence is highly conserved among vertebrates, and insulin from one mammal almost certainly is biologically active in another.
28 INSULIN BIOCHEMISTRY Proinsulin- inactive chain of 86 a.a. C Peptide- connecting peptide of 31 a.a.Insulin – remaining 51 a.a. made up of chains A and B
29 INSULIN SECRETION Pancreas secrets 40-50 units insulin/day Basal insulin conc. in fasting state 10 U/mLFood ingestion, insulin conc.8-10 min. initial increase30-45 min peakmin. returns to baseline values.
31 INSULIN Control of Insulin Secretion Insulin is secreted primarily in response to elevated blood concentrations of glucoseSome neural stimuli (e.g. site and taste of food) and increased blood concentrations of other fuel molecules, including amino acids and fatty acids, also promote insulin secretion.Glucose is transported into the B cell by facilitated diffusion through a glucose transporter; elevated concentrations of glucose in extracellular fluid lead to elevated concentrations of glucose within the B cell.
32 INSULIN Insulin Control of Insulin Secretion + - Parasympathetic Nervous SystemGlucose StimulusD i g e s t i v ehormones-Sympathetic nervous symtem-Sympathetic Nervous systemSomastatinGrowth hormone ACTHGlucagonInsulin+-
33 INSULIN Control of Insulin Secretion Elevated concentrations of glucose within the B cell ultimately leads to membrane depolarization and an influx of extra cellular calcium.The resulting increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules.An increased level of glucose within B cells also appears to activate calcium-independent pathways that participate in insulin secretion.
35 INSULIN Physiologic Effects of Insulin Insulin is a key player in the control of intermediary metabolism.Insulin has profound effects on:Carbohydrate metabolismLipid metabolismSignificant influences on protein and mineralmetabolismConsequently, derangements in insulin signaling have widespread and devastating effects on many organs and tissues.
36 INSULIN The Insulin Receptor and Mechanism of Action Like the receptors for other protein hormones, the receptor for insulin is embedded in the plasma membrane.The insulin receptor is composed of two alpha subunits and two beta subunits linked by disulfide bonds.The alpha chains are entirely extra cellular and house insulin binding domains, while the linked beta chains penetrate through the plasma membrane.
37 INSULIN Insulin and Carbohydrate Metabolism Insulin facilitates entry of glucose into muscle, adipose and several other tissues.The only mechanism by which cells can take up glucose is by facilitated diffusion through a family of hexose transporters of many tissues - muscle being a prime exampleThe major transporter used for uptake of glucose called GLUT4 is made available in the plasma membrane through the action of insulin.Binding of insulin to receptors on such cells leads rapidly to fusion of those vesicles with the plasma membrane and insertion of the glucose transporters, thereby giving the cell an ability to efficiently take up glucose.
38 INSULIN Insulin and Carbohydrate Metabolism It should be noted here that there are some tissues that do not require insulin for efficient uptake of glucose: important examples are brain and the liver.This is because these cells don't use GLUT4 for importing glucose, but rather, another transporter that is not insulin-dependent.Insulin stimulates the liver to store glucose in the form of glycogen. A large fraction of glucose absorbed from the small intestine is immediately taken up by hepatocytes, which convert it into the storage polymer glycogen.When the supply of glucose is abundant, insulin “tells" the liver to bank as much of it as possible for use later.
42 INSULIN Insulin and Lipid Metabolism When the liver is saturated with glycogen, any additional glucose taken up by hepatocytes is shunted into pathways leading to synthesis of fatty acids, which are exported from the liver as lipoproteins.The lipoproteins are ripped apart in the circulation, providing free fatty acids for use in other tissues, including adipocytes, which use them to synthesize triglyceride.Insulin inhibits breakdown of fat in adipose tissue by inhibiting the intracellular lipase that hydrolyzes triglycerides to release fatty acids.
43 INSULIN Other Notable Effects of Insulin Insulin also stimulates the uptake of amino acids, again contributing to its overall anabolic effect.Insulin also increases the permeability of many cells to potassium, magnesium and phosphate ions.The effect on potassium is clinically important. Insulin activates Na/K ATPase in many cells, causing a flux of potassium into cells.
44 What happens to glucose in the body? EXTERNAL DIETDIGESTIONGLUCOSEGlycolysisENERGYGlycogenSTORAGELipogenesisFATSGlycogenesisGlycogenolysisPyruvates+LactatesAmino acidsGlycerolINTERNALGluconeogenesis(Liver)
45 What happens between meals? Blood GlucoseLiver mobilizes glycogen storesBreak down of Glycogen=GLYCOGENOLYSISGlucoseBlood streamN.B. The liver is the only organ able to liberate glucose from its glycogen stores
47 Insulin and Glucagon Regulate Normal Glucose Homeostasis (α cell)Fasting stateFed statePancreasInsulin(β cell)Insulin and Glucagon Regulate Normal Glucose HomeostasisNormal glucose homeostasis is maintained in large part through a feedback relationship between insulin, glucagon, and circulating glucose.1Fasting StateIn the fasting state, pancreatic alpha (α) cells release glucagon.1,2 Glucagon release is triggered by a fall in the plasma glucose level.1 Concomitantly, the pancreatic beta (β) cells secrete less insulin.Glucagon directs the liver to break down stored glycogen into glucose (glycogenolysis).1 The liver also generates new glucose (gluconeogenesis) during fasting. The end result is that the liver releases glucose into the bloodstream, thereby raising the plasma glucose level and maintaining homeostasis.Fed StateIn the fed state, meal-derived glucose enters the bloodstream, and the β cells detect the rise in glucose level and respond by promptly releasing insulin.1Insulin signals other tissues in the body to take in glucose to be used as energy or stored for later use.1 Insulin also signals the liver to decrease glucose production, thus suppressing hepatic glucose production. The net result is the lowering of the plasma glucose level.In the fed state, release of glucagon is suppressed, which also contributes to a decrease in glucose production.1Normal functioning of this feedback loop helps maintain glucose homeostasis.Purpose:To explain how normal physiology works in order to set the foundation for understanding the physiologic defects in type 2 diabetes. This slide demonstrates the key regulatory roles of insulin and glucagon on glucose homeostasis in both the fasting and fed states.Take-away:Glucose homeostasis under normal conditions is well regulated.Glucose outputGlucose uptakeLiverBlood glucoseMuscleAdipose tissuePorte D Jr, Kahn SE. Clin Invest Med. 1995;18:247–254.Adapted with permission from Kahn CR, Saltiel AR. In: Kahn CR et al, eds. Joslin’s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:145–168.References1. Porte D Jr, Kahn SE. The key role of islet dysfunction in type II diabetes mellitus. Clin Invest Med ;18:247–254.2. Unger RH. Glucagon and the insulin: glucagon ratio in diabetes and other catabolic illnesses. Diabetes ;20:834–838.
48 Major Pathophysiologic Defects in Type 2 Diabetes Hepatic glucoseoutputInsulin resistanceGlucose uptakeGlucagon(α cell)Insulin(β cell)LiverHyperglycemiaIslet-cell DysfunctionMuscleAdipose tissuePancreasMajor Pathophysiologic Defects in Type 2 DiabetesThis diagram depicts the impact of type 2 diabetes on the feedback loop that regulates glucose homeostasis.In type 2 diabetes, insulin resistance is increased and insulin secretion is impaired.1Most patients with type 2 diabetes have insulin resistance. Normally, pancreatic β cells increase insulin secretion to compensate for insulin resistance. However, when β-cell function is impaired, hyperglycemia develops.1By the time diabetes is diagnosed, β-cell function has already decreased substantially and continues to decline over time.1Once insulin secretion is impaired, an imbalance between insulin and glucagon can develop. Elevated glucagon levels lead to an increase in hepatic glucose production, which leads to an increase in blood glucose.1Likewise, with decreased secretion of insulin, less glucose is taken up by muscle and adipose tissue.2Purpose:To explain the 3 core defects of type 2 diabetes.Take-away:Insulin resistance, β-cell dysfunction, and elevated hepatic glucose production each contribute to hyperglycemia in type 2 diabetes.Adapted with permission from Kahn CR, Saltiel AR. In: Kahn CR et al, eds. Joslin’s Diabetes Mellitus. 14th ed. Lippincott Williams & Wilkins; 2005:145–168; Del Prato S, Marchetti P. Horm Metab Res. 2004;36:775–781; Porte D Jr, Kahn SE. Clin Invest Med. 1995;18:247–254.References1. Del Prato S, Marchetti P. Beta- and alpha-cell dysfunction in type 2 diabetes. Horm Metab Res. 2004;36:775–781.2. Porte D Jr, Kahn SE. The key role of islet dysfunction in type 2 diabetes mellitus. Clin Invest Med. 1995;18:247–254.
50 The Incretin AxisPeptides released by the gut throughout the day and increased in response to meals — participate in normal glucoregulationGLP-1 and GIP are the dominant incretinsBoth stimulate insulin release from β-cells and GLP-1 inhibits glucagon release from -cellsThe incretin axis is abnormal in patients with T2DMReduced release of GLP-1Reduced response to GIPDrucker DJ. Diabetes Care. 2003: ; Ahren B. Curr Diab Rep. 2003;3: ; Drucker DJ Gastroenterology. 2002;122: ; Dunning BE, et al. Diabetologia. 2005;48:ADA 2006 Late Breaking Clinical Presentation (Stein).
51 Demonstrated Effects of the Incretin Hormones GLP-1 and GIP Is released from L cells in ileum and colonStimulates insulin response from β cells in a glucose-dependent mannerInhibits gastric emptyingReduces food intake and body weightInhibits glucagon secretion from α cells in a glucose-dependent mannerEffect on β-cell turnover in preclinical modelsIs released from K cells in duodenumStimulates insulin response from β cells in a glucose-dependent mannerHas minimal effects on gastric emptyingHas no significant effects on satiety or body weightDoes not appear to inhibit glucagon secretion from α cellsEffect on β-cell turnover in preclinical modelsDemonstrated Effects of the Incretin Hormones GLP-1 and GIPGLP-1 and GIP are the currently identified incretin hormones.An incretin is a hormone with the following characteristics1,2:- It is released from the intestine in response to ingestion of food, particularly glucose.- The circulating concentration of the hormone must be sufficiently high to stimulate the release of insulin.- The release of insulin in response to physiological levels of the hormone occurs only when glucose levels are elevated (glucose-dependent).GIP and GLP-1 are hormones that fulfill these 3 characteristics, qualifying them as incretins.2In the fasting state, GIP and GLP-1 circulate at very low levels. Their levels rapidly increase after food ingestion and play a role in the release of insulin.3,4GLP-1 stimulates insulin response from β cells in a glucose-dependent manner and suppresses glucagon secretion from α cells in a glucose-dependent manner. GIP also potentiates insulin release from β cells in a glucose-dependent manner.5 Other effects of GLP-1 and GIP are summarized on the slide.Purpose:To describe the 2 main incretins, GLP-1 and GIP.Take-away:Both GLP-1 and GIP play key roles in glucose homeostasis. GLP-1 and GIP both stimulate insulin secretion in a glucose-dependent manner, and GLP-1 also inhibits glucagon secretion in a glucose-dependent manner.Meier JJ et al. Best Pract Res Clin Endocrinol Metab. 2004;18:587–606; Drucker DJ. Diabetes Care. 2003;26:2929–2940. Farilla L et al. Endocrinology. 2003;144:5149–5158.References1. Creutzfeldt W. The [pre-] history of the incretin concept. Regul Pept. 2005;128:87–91.2. Creutzfeldt W. The entero-insular axis in type 2 diabetes – incretins as therapeutic agents. Exp Clin Endocrinol Diabetes. 2001;109(suppl 2):S288-S303.3. Gautier JF, Fetita S, Sobngwi E, Salaün-Martin C. Biological actions of the incretins GIP and GLP-1 and therapeutic perspectives in patients with type 2 diabetes. Diabetes Metab. 2005;31:233–242.4. Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans. Am J Physiol Endocrinol Metab. 2004;287:E199–E206.5. Meier JJ, Nauck MA. Glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide. Best Pract Res Clin Endocrinol Metab. 2004;18:587–606.
52 Role of Incretins in Glucose Homeostasis Ingestion of foodβ cellsα cellsRelease of gut hormones — incretins*PancreasGlucose-dependent Insulin from β cells(GLP-1 and GIP)Glucose uptake by musclesGlucose dependent Glucagon from α cells(GLP-1)GI tractActiveGLP-1 & GIPDPP-4 enzymeInactive GIPInactive GLP-1*Incretins are also released throughout the day at basal levels.Glucose production by liverBlood glucose in fasting and postprandial statesRole of Incretins in Glucose HomeostasisAfter food is ingested, GIP is released from K cells in the proximal gut (duodenum), and GLP-1 is released from L cells in the distal gut (ileum and colon).1–3 Under normal circumstances, DPP-4 rapidly degrades these incretins to their inactive forms after their release into the circulation.1,2Actions of GLP-1 and GIP include stimulating insulin response in pancreatic β cells (GLP-1 and GIP) and suppressing glucagon production (GLP-1) in pancreatic α cells when the glucose level is elevated.2,3 The subsequent increase in glucose uptake in muscles3,4 and reduced glucose output from the liver2 help maintain glucose homeostasis.Thus, the incretins GLP-1 and GIP are important glucoregulatory hormones that positively affect glucose homeostasis by physiologically helping to regulate insulin in a glucose-dependent manner.2,3 GLP-1 also helps to regulate glucagon secretion in a glucose-dependent manner.2,5Purpose:To demonstrate how the incretin pathway is part of the normal physiology of glucose homeostasis.Take-away:After food ingestion, incretins stimulate insulin release from β cells and suppress glucagon release from α cells in a glucose-dependent manner, resulting in downstream effects that regulate glucose homeostasis. The activity of the incretins is limited by the DPP-4 enzyme.Adapted from Kieffer TJ, Habener JF. Endocr Rev. 1999;20:876–913; Ahrén B. Curr Diab Rep. 2003;2:365–372; Drucker DJ. Diabetes Care. 2003;26:2929–2940; Holst JJ. Diabetes Metab Res Rev. 2002;18:430–441.References1. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999;20:876–913.2. Ahrén B. Gut peptides and type 2 diabetes mellitus treatment. Curr Diab Rep. 2003;3:365–372.3. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care. 2003;26:2929–2940.4. Holst JJ. Therapy of type 2 diabetes mellitus based on the actions of glucagon-like peptide-1. Diabetes Metab Res Rev. 2002;18:430–441.5. Nauck MA, Kleine N, Ørskov C, Holst JJ, Wilms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993;36:741–744.
53 Fate of GlucoseIf energy is needed immediately, glucose is metabolized to produce energy via glycolysis.If more glucose is available than what the cells need immediately for energy, the extra glucose is converted to glycogen via a process called glycogenesis. Glycogenesis occurs primarily in liver cells and, to a limited extent, in muscle cells.When glucose is not immediately required for energy and the storage capacity for glycogen is reached in the liver and muscle, additional glucose can be oxidized or converted to fat.
57 Natural History Of Disease Progression Macrovascular complicationsMicrovascular complicationsb-cell functionInsulinresistanceBloodglucoseThere is a temporal relationship between insulin resistance, insulin secretion, and the development of diabetes.In the early stages of pathogenesis, as insulin resistance rises, there is a compensatory increase in insulin secretion and the individual remains normoglycaemic.1In the long term, if the -cells begin to fail, insulin secretion falls, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) develop, and hyperglycaemia reaches levels defined as type 2 diabetes.1 However, diabetes is not always diagnosed until many years later.Development of diabetes is associated with the development of serious complications that begin before type 2 diabetes is diagnosed.2 The risk of complications increases as the disease progresses.3There are two potential approaches to delaying the progression of the disease and its associated complications: firstly, prevention interventions at the stage of IGT/IFG, and secondly, treatment interventions to delay disease progression following diagnosis.DeFronzo RA. Med Clin N Am 2004; 88:787–835.Hu FB, et al. Diabetes Care 2002; 25:1129–34.Stratton IM, et al. UKPDS 35. BMJ 2000; 32:405–412.–10PreventionTreatment10YearsDiagnosisIGT/IFGType 2 diabetesDeFronzo RA. Med Clin N Am 2004; 88:787–835.
58 Glucose Homeostasis Pancreas The presence of glucose in the bloodstream will entice the beta cells of the pancreas to produce a hormone called insulin.Pancreas
59 Insulin Action in Normal Tissues (Cellular Level) (GLUT 4)Glucose transport proteinsInsulin receptorsCell
60 Insulin Action in Normal Tissues (Cellular Level) (GLUT 4)Glucose transport proteinsInsulin receptorsCell
61 Insulin Action in Normal Tissues (Cellular Level) (GLUT 4)Glucose transport proteinsInsulin receptorsCell
62 Insulin Action in Normal Tissues (Cellular Level) (GLUT 4)Glucose transport proteinsInsulin receptorsCell
65 Insulin Resistance Cell Cell (GLUT 4) Glucose transport proteins Insulin receptorsCellInsulin receptors(GLUT 4)Glucose transport proteinsCellIn the case, the signal transmitted by the insulin IS MUCH WEAKER than the ones transmitted in the normal cells.
66 Insulin Resistance Cell Insulin receptors As a result, only a few glucose could enter the cell. Less Glucose ULITIZATION.Consequently, both blood glucose and insulin levels are elevated.Cell
67 POST-Receptor Level Early stage - normal to IGT INSULIN RESISTANCE Phase: Disease Progression Stage :POST-Receptor Level Early stage - normal to IGTReceptor Level Hyperinsulinemia- IGT to T2DAs a result, only a few glucose could enter the cell. Less Glucose ULITIZATION.Consequently, both blood glucose and insulin levels are elevated.
68 INSULIN RESISTANCE Phase: Disease Progression Stage : Pre- Receptor Level Latter Part Stage - Beta-cell Dysfuntion (Pancreatic exhaustion)As a result, only a few glucose could enter the cell. Less Glucose ULITIZATION.Consequently, both blood glucose and insulin levels are elevated.
70 ADA and IDF Guidelines: Treatment Goals for HbA1c, FPG, and PPG ParameterNormal LevelADA GoalIDF GoalFPG, mg/dL (mmol/L)<110 (<6.1)90–130 (5.0–7.2)<110 (<6.1)PPG, mg/dL (mmol/L)<140 (<7.8)<180(<10.0)<145(<8.1)HbA1c4%–6%<7%*<6.5%ADA and IDF Guidelines: Treatment Goals for HbA1c, FPG, and PPGThe table presents guidelines from the American Diabetes Association (ADA) and the International Diabetes Federation (IDF).1,2The ADA and IDF recommend slightly different treatment goals of FPG, PPG, and HbA1c levels.1,2 Both organizations emphasize the importance of good glycemic control.The ADA suggest that the goal of treatment in the management of diabetes should be an HbA1c value less than 7%.1 IDF suggests an HbA1c goal of less than 6.5%.2The ADA target of FPG levels of 90 to 130 mg/dL (5.0–7.2 mmol/L) is based on the estimate of the range of average glucose values that would be associated with a low risk of hypoglycemia and HbA1c less than 7%.1 IDF recommends a target FPG level of less than 110 mg/dL (<6.1 mmol/L).2The ADA recommend reducing average PPG values (2-hour oral glucose tolerance testing [OGTT]) to less than 180 mg/dL (10.0 mmol/L),1 whereas IDF suggests a target PPG level of less than 145 mg/dL (<8.1 mmol/L).2Purpose:To provide a reminder of current ADA and IDF guidelines for treating type 2 diabetes.Take-away:It is important to target all 3 treatment goals for glucose control HbA1c, FPG, and PPG).*The HbA1c goal of an individual patient is to achieve an HbA1c as close to normal (<6%) as possible without significant hypoglycemia.ADA=American Diabetes Association; IDF=International Diabetes Federation.ADA. Diabetes Care. 2007;30(suppl 1):S4–S41; International Diabetes Federation. 2005:1–79.References1. American Diabetes Association. Standards of Medical Care in Diabetes–2007. Diabetes Care. 2007;30(suppl 1): S4–S41.2. International Diabetes Federation. Global Guidelines for Type 2 Diabetes.2005:1-79. Available at Accessed on August 2005.
71 Therapy for Type 2 DM Lifestyle changes Pharmacologic Diet ExerciseStop smokingGlycemic controlPrevent complicationsPrevent disease progressionPharmacologicGlycemic controlPrevent complicationsPrevent disease progressionTreat co-morbid conditionsMinimal side effects
72 Nutrient Composition of the Therapeutic Lifestyle Change (TLC) Diet Recommended IntakeCarbohydrate50% to 60% of total calories; mostly from food rich in complex carbohydratesFiber20-30 g/dayProteinApproximately 15% of total caloriesCholesterol<200 mg/dayTotal CaloriesBalance energy intake and expenditure; should include at least moderate physical activityExecutive Summary of the Third Report of the National Cholesterol Education Program(NCEP) Expert Panel Detection, Evaluation, and Treatment of High Blood Cholesterolin Adults (Adult Treatment Panel III). JAMA. 2001;285:
73 Primary Sites Of Action Of Oral Anti-diabetic Agents ThiazolidinedionesBiguanidesMuscleAdipose tissueLiverDPP-4 inhibitorsDPP-4PancreasStomachInsulinGlucoseThiazolidinediones (e.g. rosiglitazone) decrease insulin resistance in adipose tissue, skeletal muscle and liver. In addition, they may have a beneficial effect on -cell function. They are direct insulin sensitizers that act as agonists for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARg). PPARg increases the transcription of certain insulin-sensitive genes, thereby improving insulin sensitivity.Biguanides such as metformin primarily suppress hepatic glucose output. In addition, they enhance insulin sensitivity and stimulate insulin-mediated glucose disposal. They do not stimulate insulin secretion.Sulphonylureas and meglitinides both lower fasting blood glucose concentrations, primarily by stimulating insulin secretion from the pancreas.Alpha-glucosidase inhibitors such as acarbose delay digestion and absorption of carbohydrates in the gastrointestinal tract. They inhibit the enzyme a-glucosidase, responsible for the metabolism of complex carbohydrates into absorbable monosaccharides.Glucagon-like peptide 1 (GLP-1) analogues mimic GLP-1, a gastrointestinal hormone that increases insulin secretion from the pancreas and inhibits glucagon release.Dipeptidyl peptidase 4 (DPP-4) inhibitors block the DPP-4 enzyme which would otherwise inactivate GLP-1.Kobayashi M. Diabetes Obes Metab 1999; 1(Suppl. 1):S32–S40. Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309–329. Pratley RE & Salsali A. Curr Med Res Opin 2007; 23:919–931. Todd JF & Bloom SR. Diabet Med 2007; 24:223–232.GLP-1a-glucosidase inhibitorsSulphonylureas and meglitinidesGLP-1 analoguesGutAdapted from Kobayashi M. Diabetes Obes Metab 1999; 1(Suppl. 1):S32–S40. Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309–329. Pratley RE & Salsali A. Curr Med Res Opin 2007; 23:919–931. Todd JF & Bloom SR. Diabet Med 2007; 24:223–232.
74 Insulin Secretagogues: Basic Characteristics Mechanism of action:Increase basal and postprandial insulin secretionTherapeutic efficacy:Decreases HbA1c 1%-2%*Recommended dosing:Sulfonylureas: 1-2x dailyRepaglinide, nateglinide: 3x dailyAdverse effects:Weight gain, hypoglycemiaThe Insulin Secretagogues: Basic Characteristics of the Meglitinides and the SulfonylureasThe insulin secretagogues, which include the meglitinides and the sulfonylureas, lower plasma glucose by augmenting insulin secretion by the pancreatic beta-cells and are thus only effective if functioning pancreatic beta-cells are present. During treatment with the insulin secretagogues, a reduction of glycosylated hemoglobin (HbA1c) by approximately 1.0% to 2.1% may be expected. The sulfonylureas may be given once or twice daily, while repaglinide, the only agent in the meglitinides group currently available in the United States, is given three times daily. Weight gain is the most notable side effect; allergy occurs rarely. The main risk accompanying sulfonylurea treatment is the potential for hypoglycemia.Amaryl PI. Hoechst Marion Roussel, August 1997; DiaBeta PI. Hoechst Marion Roussel, September 1997; Glucotrol PI. Pfizer, September 1993; Glynase PI. Pharmacia & Upjohn, January 1999; Micronase PI. Pharmacia & Upjohn, February 1999; Prandin PI. Novo Nordisk, October 1998.*Results vary according to clinical trial design, individual patient characteristics, and data analyses.Amaryl PI. Hoechst Marion Roussel, August 1997; DiaBeta PI. Hoechst Marion Roussel, September 1997; Glucotrol PI. Pfizer, September 1993; Glynase PI. Pharmacia & Upjohn, February 1999; Micronase PI. Pharmacia & Upjohn, January 1999; Prandin PI. Novo Nordisk, October 1998.
85 Thiazolidinediones Insulin sensitizer Slight decrease Decreased Hepatic (Inc LFT in Troglitazone)Drug interactions (few)Weight gain ? Edema ?SafetyDurableEffectiveness over timeIncreasedWeightModerate to lateOnset of actionGenerally positiveLipidsNo effectHypoglycaemiaDecreasedSerum insulinSlight decreaseHepatic glucose outputInsulin sensitivityInsulin sensitizerAction
86 Indications for Insulin in Type 2 Diabetes Hyperglycemia despite maximum doses of oral agentsDecompensation due to intercurrent events e.g., infection, acute injury, or other stressDevelopment of severe hyperglycemia with ketonemia and/or ketonuriaUncontrolled weight loss
87 Indications for Insulin in Type 2 Diabetes Perioperative in patients undergoing surgeryPregnancyRenal or hepatic diseaseAllergy or other serious reaction to oral agents
88 Algorithm for the Metabolic Management of Type 2 Diabetes Tier 1: Well-validated core therapiesLifestyle + Metformin+Basal insulinSulfonylureaSTEP 2Lifestyle + Metformin+Intensive insulinSTEP 3At diagnosis:Lifestyle+MetforminSTEP 1Tier 2: Less well-validated therapiesLifestyle + Metformin+ GLP-I agonistsNo hypoglycemiaWeight lossNausea/vomiting+ PioglitazoneOedema/CHFBone lossLifestyle + Metformin+ Pioglitazone+ Sulfonylurea+ Basal Insulin
89 Type 2 diabetes is associated with serious complications StrokeDiabetic Retinopathy2- to 4-fold increase incardiovascular mortality and stroke5Leading causeof blindnessin adults1,2Cardiovascular Disease8/10 individuals with diabetes die from CV events6Serious microvascular and macrovascular complications of type 2 diabetes have a devastating effect on quality of life and impose a heavy burden on healthcare systems.Diabetic retinopathy: present in 21% of people at the time type 2 diabetes is diagnosed,1 diabetic retinopathy is the leading cause of new blindness among adults aged 20–74 years.2Diabetic nephropathy: present in 18% of people diagnosed with diabetes;3 diabetes is a leading cause of end-stage renal disease.4Stroke: diabetes is associated with a 2- to 4-fold increase in cardiovascular mortality and stroke.5Cardiovascular disease: 75% of individuals with type 2 diabetes die from cardiovascular causes.6Diabetic neuropathy: present in 12% of people at diagnosis,1 diabetic neuropathy affects approximately 70% of people with diabetes7 and is a leading cause of non-traumatic lower extremity amputations.8In the UKPDS, 50% of individuals with diabetes already had complications at diagnosis.9 Early detection and treatment of diabetes is essential in order to reduce the impact of its serious complications.1UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672– Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, Blackwell Sciences. 7King’s Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79. 9UKPDS Group. Diabetologia 1991; 34:877–890.DiabeticNephropathyDiabetic NeuropathyLeading cause ofend-stage renal disease3,4Leading cause of non-traumatic lower extremity amputations7,81UK Prospective Diabetes Study Group. Diabetes Res 1990; 13:1–11. 2Fong DS, et al. Diabetes Care 2003; 26 (Suppl. 1):S99–S102. 3The Hypertension in Diabetes Study Group. J Hypertens 1993; 11:309–317. 4Molitch ME, et al. Diabetes Care 2003; 26 (Suppl. 1):S94–S98. 5Kannel WB, et al. Am Heart J 1990; 120:672–676. 6Gray RP & Yudkin JS. Cardiovascular disease in diabetes mellitus. In Textbook of Diabetes 2nd Edition, Blackwell Sciences. 7King’s Fund. Counting the cost. The real impact of non-insulin dependent diabetes. London: British Diabetic Association, Mayfield JA, et al. Diabetes Care 2003; 26 (Suppl. 1):S78–S79.
91 Biology of Microvascular Complications HyperglycemiaEyeKidneyNervesRetinopathyCataractGlaucomaNephropathyMicroalbuminuriaGross albuminuriaNeuropathyPeripheralAutonomicBlindnessKidney failureAmputationDeath and/or disability
92 Biology of Macrovascular Complications Metabolic injury to large vesselsHeartBrainExtremitiesCardiovascular diseaseAcute coronary syndromeMyocardial infarction (MI)Congestive heart failureCerebrovascular diseaseTransient ischemic attackStrokeCognitive impairmentPeripheral vascular syndromeUlcersGangreneAmputations
93 Impact of Type 2 Diabetes on Macrovascular Disease Largest cause of morbidity and mortalityRisk of CVD increased 2- to 4-foldHigher case fatality vs non diabetic individualsReduced survival post–MI, post–CABG, and particularly post–PTCARisk of stroke and peripheral vascular disease substantially increasedIn addition to the 2- to 4-fold increased risk of CVD, type 2 diabetes is associated with a higher case fatality post–myocardial infarction (MI) and a poorer outcome after interventional procedures. People with diabetes experience high rates of out-of-hospital mortality. This argues for aggressive primary prevention.Betteridge DJ. Diabetic dyslipidaemias. Acta Diabetol. 1999;36:S25-S29.Nesto R. CHD: a major burden in type 2 diabetes. Acta Diabetol. 2001;38:S3-S8.Betteridge DJ. Acta Diabetol. 1999;36:S25-S29. Nesto R. Acta Diabetol. 2001;38:S3-S8.93
94 Diabetic Macroangiopathy AtherosclerosisAtherosclerosis begins to appear in most diabetics whatever their age, within a few year of onset of diabetes.The susceptibility of diabetics to atherosclerosis is due to several factors:HyperlipidemiaHDL Levels are reduced in type 2 diabeticsDiabetics have increased platelet adhesiveness and response to aggregative agents.Most type 2 diabetic patients are obese and hypertensive which further contributes to Atherosclerosis
95 CLINICAL PRESENTATION OF MACROANGIOPATHY StrokeEstimated relative risk of stroke in diabetes mellitus:2 – 8%Mainly due to the atherosclerosis of the cerebral vessels leading to the rupture and ischemia of the cerebral tissue.Coronary Heart Diseases√ Ischaemic heart diseaseType 2 diabetics develop CHD at a young ageThe 5-Years risk of ischaemic events is doubledWorse outcome post –MI
97 PATHOPHYSIOLOGY OF THE DIABETIC FOOT atherosclerosisOf the leg vesselsInfection(contributes to tissue necrosis)Peripheralneuropathyclaudicationulcerationgangrenerest painIschemia (Often bilateral)Sensory deficitAutonomic dysfunction
98 Diabetic NeuropathyNumbness, tingling or pain in the toes, feet, legs, hands, arms and fingersWasting of muscles of feet or handsIndigestion, nausea or vomitingDiarrhea or constipationDizziness or faintness due to a drop in postural blood pressueProblems with urinationErectile dysfunction (impotence) or vaginal drynessWeakness
100 INFECTIONS Hyperglycemia favors Development of infection Urinary tract InfectionSkin infectionRespiratory tractinfectionTreatment of infectionAnd improved blood glucoseControl
101 DIABETIC RETINOPATHYOne of the most threatening aspects of DM’s the development of visual impairmentEpidemiologyLeading cause of blindness in Western countriesRetinopathy is the most common complication of diabetes.Risk factors are: duration of diabetes, poor BG control, highBlood pressure, hypercholesterolemia, proteinuria.
102 DIABETIC RETINOPATHY Symptoms Reduction in visual acuity Reduction in visual fieldsReduction in vision of colors
103 DIABETIC NEPHROPATHYA major cause of end-stage renal disease and dialysis.The kidneys are usually the most severely damaged organs in diabeticsDiabetic nephropathy with proteinuria is a common serious complication affecting Type 1 and Type 2 diabetes.Affect 25% of the diabetics
107 Measurements Albumin to creatinine ratio 24 hour urine collection Timed collection (4 H or overnight)Screen for with reagent strips
108 False Positives Short time hyperglycemia Exercise Acute febrile illnessUTIMarked hypertensionCHF
109 Microvascular Complications of Diabetes Stages of diabetic nephropathy(Adapted from Mogensen 1999)StageUAERate(μg/min)BloodPressureGlomerularFiltration rate(GFR)HistologicalChanges1Hyperfiltration0 – 20NormalIncreased by20 – 50 %IncreasedGlomerular sizeNormoalbuminuriaBasementMembrane (BM)thickening2Microalbuminuria21 – 200Normal orelevatedStill high, butdeclines withproteinuriaBM thickeningMesangialexpansion3Proteinuria>200ElevatedDecline~10ml/min/yrPronouncedabnormalities4End-stage renal FailureHypertension<10ml/minAdvancedglomerulopathy
110 Risk Factors DM Nephropathy Poor glycemic control and insulin resistance Hypertension Albuminuria Smoking High dietary intake of protein Hyperlipidemia
111 Microvascular Complications of Diabetes Diabetic Nephropathy: Therapeutic StrategiesMicroalbuminuria predicts cardiovascular morbidity and mortality as well as renal diseaseTreatment should delay or prevent the progression of microalbuminuria to proteinuriaTrials have shown that therapeutic strategies should include:- intensive glycaemic control- aggressive control of blood pressure (ACE inhibitors)
112 Treatment Recommendations for Diabetic Patients with Albuminuria/Nephropathy In the treatment of albuminuria/nephropathy, both ACE inhibitors and ARBs can b used:In hypertensive and non-hypertensive T1 DM: ACE-inhibitors are the initial agents of choiceIn hypertensive and non-hypertensive T2 DM: ARBs are the initial agents of choiceThe new 2002 ADA Guidelines reflect the existing and more recent clinical study data in patients with type 1 and type 2 diabetes, which demonstrate the benefit of ACE-inhibitors and ARBs over other antihypertensive therapy in delaying the progression from microalbuminuria to clinical albuminuria and slowing the decline in glomerular filtration rate (GFR) in patients with albuminuria.In hypertensive and non-hypertensive type 1 diabetic patients, ACE-inhibitors are the initial agents of choice.In hypertensive and non-hypertensive type 2 diabetic patients, ARBs have been shown to reduce the rate of progression of albuminuria and clinical nephropathy and are the initial agents of choice in these patients.Diabetes Care. 2002;25(1):S33
113 Strategies for Preventing Complications of Diabetes Control blood glucoseHbA1c below 7%FBS below 110 mg%RBS below 160 mg%Control blood pressureBelow 130/80Control lipidsLDL below 100 mg%HDL above 45 for males and 55 for femalesTriglycerides below 150 mg%Weight lossStop smoking
114 Summary of Recommendations for Adults With Diabetes Glycemic ControlA1C<7.0%*Preprandial plasma glucosemg/dL ( mmol/L)Postprandial plasma glucose†<180 mg/dL (<10.0 mmol/L)Blood pressure<130/80 mmHgLipids‡LDL<100 mg/dL (<2.6 mmol/L)Triglycerides<150 mg/dL (<1.7 mmol/L)HDL>40 mg/dL (1.1 mmol/L)§*Nondiabetic range of % using DCCT-based assay†PPG made 1-4 h after beginning of meal‡NCEP/ATP III guidelines: for TG>200 mg/dL, use non-HDL cholesterol = TC-HDL§For women, HDL goal >50 mg/dLDiabetes Care 2004; 27(Suppl1):S15-S35
115 What is the Metabolic Syndrome A group of metabolic risk factors in one person. Central obesityAtherogenic dyslipidemia - mainly high triglycerides and low HDL cholesterolInsulin resistance or glucose intoleranceProthrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor [–1] in the blood)Raised blood pressure (130/85 mmHg or higher)Proinflammatory state (e.g., elevated high-sensitivity C-reactive protein in the blood)
116 (Waist circumference) Women < 50 mg/dL (1.2 mmol/L) Metabolic SyndromeClinical Identification - Any 3 of the followingAbdominal ObesityMen > 40 inches (>102 cm)Women > 35 inches (>88 cm)(Waist circumference)HIGH Triglycerides≥ 150 mg/dL(≥ 1.7 mmol/L)LOW HDL-CMen < 40 mg/dL (1.0 mmol/L)Women < 50 mg/dL (1.2 mmol/L)SLIDE 4: NCEP Guidelines, defines metabolic syndrome as 3 out of 5 of the ff parameters (read).Fasting Glucose≥100 mg/dL≥ 5.5 mmol/LHypertension≥ 130 / ≥ 85 mmHgNCEP-ATP III – JAMA 2001
117 New IDF Definition of Metabolic Syndrome Waist circumference Plus 2 of the ff:(cm)Europids FBS >5.6 (100mg/dL)>94 male>80 female TRIG >1.7 (150mg/dL)South Asians>90 male HDL < 0.9 (<40mg/dL) M>80 female <1.1 (<50mg/dL) FChinese>90 male BP >130 systolic>80 female >85 diastolicJapanese>85 male>90 female
118 Risk Factors Among Filipinos Prevalence (%)Low HDLObesity (BMI>30)Obesity (WHR 1/0.85)SmokingHypertriglyceridemiaHypertensionDM * *4** **6.6 ***Metabolic Syndrome (NCEP)*FBS > 125 mg/dL ** FBS or history *** FBS ≥101 mg/dLMorales D et al. for the NNHeS Group. PSH-PLS Convention. Feb 2005.Sy R et al. PJIM. 2003; 41: 1.-6.
119 Risk Factors for Metabolic Syndrome genetic predispositionexcess body fat (abdominal obesity)sedentary lifestylephysical inactivityFord ES et al. JAMA. 2002; 287:
120 While the pathogenesis of the metabolic syndrome and each of its components is complex and not well understood, central obesity and insulin resistance are acknowledged as important causative factors.
121 IDF Consensus 2004 Recommendations for Treatment Primary InterventionIDF recommends that primary management for the MS is healthy lifestyle promotion. This includes :* moderate calorie restriction ( to achieve a 5-10% loss of BW in the 1st year )* moderate increase in physical activity* change in dietary composition
122 IDF Consensus 2004 Recommendations for Treatment Secondary intervention* In people for whom lifestyle change is not enough and who are considered to be at high risk for CVD, drug therapy may be required to treat the metabolic syndrome.* However, specific pharmacological agents are not yet available.* It is currently necessary instead to treat the individual components of the metabolic syndrome.
123 Atherogenic dyslipidemia Primary aims for therapy : IDF recommended treatment of the individual components of the metabolic syndrome.Atherogenic dyslipidemiaPrimary aims for therapy :* Lower Tg* Raise HDL* Reduce LDLOptions :* Fibrates* Statins
124 Elevated blood pressure IDF recommended treatment of the individual components of the metabolic syndrome.Elevated blood pressureIn patients with established diabetes, anti-HPN therapy should be introduced at BP ≥130/≥80 mmHg.Options :* ACEI and ARB. Effect of lowering of BP per se more important than the drug itself?* No particular agents have been identified as being preferable for HPN patients with MS.
125 Insulin resistance and hyperglycemia IDF recommended treatment of the individual components of the metabolic syndrome.Insulin resistance and hyperglycemiaThere is growing interest in the possibility that drugs that reduce IR will delay the onset of type 2 DM and will reduce the CVD risk when the MS is present.
126 Cardiovascular Risk Factors and Therapies ↑ LDL cholesterol↓ HDL cholesterol↑ Triglycerides↑ Blood Pressure↑ Blood Glucose↑ Waist Circumference↓ Insulin Sensitivity↑ Thrombotic riskLipid ModifiersNCEP-ATP III / IDF criteria for the metabolic syndromeAnti-hypertensivesAnti-diabetic agentsWeight Loss Agents + Diet and exerciseInsulin sensitizersAnti-platelet agents