Presentazione sul tema: "Il Diabete di Tipo 2 Emanuele Bosi Università Vita-Salute San Raffaele"— Transcript della presentazione:
1 Il Diabete di Tipo 2 Emanuele Bosi Università Vita-Salute San Raffaele Corso di Endocrinologia e Malattie del RicambioUniversità Vita-Salute San RaffaeleA.A
2 Il Diabete Mellito di tipo 2 Forma di diabete ad esordio prevalentemente adulto, caratterizzata da insulino-resistenza ed insulino deficienza relativa.Normalmente non richiede terapia insulinicaEziologia ignota:- forte componente genetica (concordanza gemelli identici >90%) a localizzazione sconosciuta.- fattori di rischio: sovrappeso e obesità, sedentarietà, età, ipertensione arteriosa, dislipidemiaFenotipo fisiopatologico relativamente eterogeneoNon evolve mai in chetoacidosi; in casi estremi coma iperosmolarePer molti anni può decorrere in modo totalmente asintomaticoSi associa ad un aumentato rischio di morbosità e mortalità cardiovascolare anche per livelli glicemici modestamente elevati
5 Worldwide prevalence of diabetes in 2000 Number of persons< 5,0005,000–74,00075,000–349,000350,000–1,499,0001,500,000–4,999,000> 5,000,000No data availableTotal cases 150 million adultsAdapted from WHO Diabetes Programme Facts and Figures: Accessed 1 August, 2006.
6 Worldwide prevalence of diabetes in 2030 (projected) Number of persons< 5,0005,000–74,00075,000–349,000350,000–1,499,0001,500,000–4,999,000> 5,000,000No data availableTotal cases > 300 million adultsAdapted from WHO Diabetes Programme Facts and Figures: Accessed 1 August, 2006.
7 Prevalenza delle alterazioni del metabolismo dei carboidrati in Italia età come fattore di rischio Diabete di tipo 2 IGTAnni % %>>45 anni- noto- non-notoCremona Study
8 Pathophysiology and Natural History of Type 2 Diabetes
9 Abnormal Islet Function Determines the Development of IGT and T2DM in the Setting of Insulin ResistanceGenetics, age, lifestyle,environmental factorsInsulin resistanceNormal islet functionAbnormal islet functionThe development of impaired glucose homeostasis predisposing to T2DM is prompted by the occurrence of insulin resistance but then dependent on the loss of normal activity at the pancreatic islet.In healthy individuals, reductions in insulin sensitivity (insulin resistance) are offset by adaptations of insulin secretion from the -cell, resulting in normal glucose processing. Progression to impaired glucose tolerance and T2DM, on the other hand, results from a failure of this adaptive mechanism, leading to abnormal -cell function—inadequate or decreased insulin secretion causing impaired glucose uptake.1Furthermore, due to the diminished ability of muscle to store or oxidize glucose in patients with impaired glucose tolerance, lactate is released into the circulation, and inadequate insulin action in adipose tissue leads to increased glycerol and free fatty acid release. Free fatty acids provide energy for gluconeogenesis, and lactate and glycerol are gluconeogenic substrates. Thus, insulin resistance in the context of progressive islet dysfunction leads to increasingly excessive fasting and postprandial hepatic glucose production and, accordingly, hyperglycemia.Reference1. Ahren B, Pacini G. Islet adaptation to insulin resistance: mechanisms and implications for intervention. Diabetes Obes Metab. 2005;7(1):2–8.NGTIGT / T2DMT2DM = type 2 diabetes mellitus; NGT = normal glucose tolerance; IGT = impaired glucose toleranceAdapted from Ahren B, Pacini G. Diabetes Obes Metab. 2005;7(1):2–8.
10 Prediabetes (IFG/IGT) Natural history of type 2 diabetes: progressive deterioration of Islet Cell Function in the Setting of Insulin ResistancePrediabetes (IFG/IGT)DiagnosisInsulin ResistanceIslet DysfunctionNGTDiabetesAdapted from International Diabetes Center. Type 2 Diabetes BASICS. Minneapolis, MN:International Diabetes Center; 2000.
11 Insulino resistenzaDefinizione: Ridotto effetto biologico dell’insulina per difetto a localizzazione post-recettorialeEziologia: indeterminataFattori di rischio:Genetici: elevata familiarità, geni non identificatiEtàSedentarietàAlimentazioneObesità e sovrappeso
12 Insulin resistance is a common feature of many human diseases Cardiovascular diseaseHypertensionDyslipidemiaINSULINRESISTANCELiver, muscle, adipocyteendotheliumPolycystic ovarysyndrome (PCOS)ObesityType 2diabetes
13 - + - + Esempi di insulino-resistenza: Effetti dell’Insulina sulla Captazione del 2-Deossi-Glucosionel Muscolo Scheletrico Umano246810*nmol/mg per minInsulina-+-+ControlliObesiGoodyear, Giorgino et al, J Clin Invest, 1995
14 Esempi di insulino-resistenza: Stimolazione dell’Attività di PI 3-Chinasi Associata a IRS-1 nel Muscolo Umano4000Controlli3000ObesiUnità Arbitrarie2000**100021530minuti di stimolazione con insulina 100 nMGoodyear, Giorgino et al, J Clin Invest, 1995
15 Obesità come fattore di rischio per diabete di tipo 2 242016Rischio Relativo1284<7171–75.976–8181.1–8686.1–9191.1–96.396.4Circonferenza addominale (cm)Carey et al., Am J Epidemiol, 1997
16 b-Cell Function Insulin Sensitivity b-Cell Function Declines While Insulin Sensitivity Remains Stable in Type 2 Diabetes8060b-Cell FunctionInsulin Sensitivity6040HOMA (%)40HOMA (%)2020246246Years from diagnosisYears from diagnosis10-year follow-up of the Belfast Diet Study: Data from 67 newly diagnosed subjects with type 2 diabetes mellitus (N=432) who required oral antihyperglycemic therapy or insulin due to secondary failure of diet therapy at 5–7 years.HOMA=Homeostasis Model Assessment; data expressed as percentages of values in lean nondiabetic reference population.Adapted from Levy J et al. Diabet Med. 1998;15:290–296.
17 Hypothetical Model for Postnatal Pancreatic ß-Cell Growth in Humans CJ Rhodes, Science, 2005
18 -cell function (%, HOMA) UKPDS: Loss of b-cell function is the major determinant of disease progression in T2DMSulphonylureaAt start of UKPDS, -cell function was already compromised-cell function deteriorates over time (~4%/year)Metformin100Diet8060-cell function (%, HOMA)Disease progression in type 2 diabetesAs UKPDS demonstrated, even with intensive therapy, target glycaemic levels are not maintained long-term. One of the main reasons for this is that type 2 diabetes is a progressive disease characterised by continued, worsening -cell failure. Indeed, at the time of diagnosis, -cell function is already markedly compromised (by approximately 50%), and, as the above slide shows, function continues to worsen, even in patients receiving pharmacological treatment. Furthermore, as the extrapolation on this slide demonstrates, -cell function may have been suboptimal for 10 years prior to diagnosis.As insulin secretagogues, the efficacy of sulphonylureas may be particularly affected by continued -cell failure because of their reliance on residual -cell function.The ideal long-term treatment for diabetes should therefore address continued -cell deterioration.ReferencesUKPDS 16. Diabetes 1995;44:1249–12584020Extrapolation of -cell function prior to UKPDS–10–8–6–4–2246UKPDSYears from diagnosisAdapted from: UKPDS 16. Diabetes 1995;44:1249–1258. HOMA: homeostasis model assessment. n=4209
19 Il volume b-cellulare è ridotto del 40% già in presenza di IFG Lo studio dei pancreasautoptici ha dimostrato cheil volume relativo b-cellularedei soggetti obesi con IFGe dei soggetti con diabetedi tipo 2 è rispettivamenteridotto del 40 e del 63%rispetto a quello dei soggettiobesi non-diabeticiButler AE, et al. Diabetes 52: , 2003
20 Determinants of progressive loss of b-cell function and mass GlucotoxicityLipotoxicitySecretory defectsInflammationIslet amyloid depositionIncretin failurealpha-cell dysfunction
21 Determinants of progressive loss of b-cell function and mass Glucotoxicity reversible, tend to resolve afterLipotoxicity normalization of glucose by any meanSecretory defectsInflammationIslet amyloid depositionIncretin failurealpha-cell dysfunction
22 Determinants of progressive loss of b-cell function and mass GlucotoxicityLipotoxicitySecretory defects: early, selective for glucoseInflammationIslet amyloid depositionIncretin failurealpha-cell dysfunction
23 Perdita della Fase Precoce della Secrezione Insulinica nel Diabete Tipo 2 ControlloDiabete di Tipo 21201008060402020 gglucosio1201008060402020 g glucosioIRI plasmatica (µU/ml)IRI plasmatica (µU/ml)––Tempo (minuti)Tempo (minuti)Ward WK, et al. Diabetes Care 1984;7:491–502.
24 Determinants of progressive loss of b-cell function and mass GlucotoxicityLipotoxicitySecretory defectsInflammation: mediated by IL-1b, IL-6, TNF-aIslet amyloid depositionIncretin failurealpha-cell dysfunction
25 Interleukin-1–Receptor Antagonist in Type 2 Diabetes Mellitus Larsen CM et Al NEJM 356: , 2007
26 Determinants of progressive loss of b-cell function and mass GlucotoxicityLipotoxicitySecretory defectsInflammationIslet amyloid deposition: IAPP (Amylin)Incretin failurealpha-cell dysfunction
27 Morfologia del pancreas endocrino nel normale, nell’obeso non diabetico enel diabetico di tipo 2Nell’obeso non-diabetico ilnumero delle isole è aumentatoe le isole tendono ad esserepiù grandi, principalmente perun aumento delle b-celluleNel diabetico di tipo 2, il numerodelle isole è diminuito, c’è unariduzione marcata delle b-cellulee compaiono depositi di amiloide(in viola) che occupano buonaparte dell’isolaRhodes C. Science 307: , 2005
30 Human islet amyloid polypeptide (IAPP) Human islet amyloid polypeptide (IAPP). The amyloidogenic region of IAPP is responsible for providing a toxic conformational structure within the islets.
31 Determinants of progressive loss of b-cell function and mass GlucotoxicityLipotoxicitySecretory defectsInflammationIslet amyloid depositionIncretin failure Incretins: GIP, GLP-1alpha-cell dysfunction
32 The Glucoregulatory Role of GLP-1 Promotes satiety and reduces appetiteDISCUSSIONBy decreasing β-cell workload and improving β-cell response, GLP-1 is an important regulator of glucose homeostasis.Upon food ingestion, GLP-1 is secreted into the circulation.GLP-1 increases β-cell response by enhancing glucose-dependent insulin secretion.BACKGROUNDGLP-1 is secreted from L cells of the small intestine.GLP-1 decreases β-cell workload, hence the demand for insulin secretion, by:Regulating the rate of gastric emptying such that meal nutrients are delivered to the small intestine and, in turn, absorbed into the circulation more smoothly, reducing peak nutrient absorption and insulin demand (β-cell workload)Decreasing postprandial glucagon secretion from pancreatic alpha cells, which helps to maintain the counterregulatory balance between insulin and glucagonReducing postprandial glucagon secretion, GLP-1 has an indirect benefit on β-cell workload, since decreased glucagon secretion will produce decreased postprandial hepatic glucose outputHaving effects on the central nervous system, resulting in increased satiety (sensation of satisfaction with food intake) and a reduction of food intakeEffect on Beta cell: Drucker DJ. Diabetes. 1998;47:Effect on Alpha cell: Larsson H, et al. Acta Physiol Scand. 1997;160:Effects on Liver: Larsson H, et al. Acta Physiol Scand. 1997;160:Effects on Stomach: Nauck MA, et al. Diabetologia. 1996;39:Effects on CNS: Flint A, et al. J Clin Invest. 1998;101:Alpha cells:↓ Postprandial glucagon secretionLiver: ↓ Glucagon reduces hepatic glucose outputBeta cells: Enhances glucose-dependent insulin secretionStomach: Helps regulate gastric emptyingAdapted from Flint A, et al. J Clin Invest. 1998;101: ; Adapted from Larsson H, et al. Acta Physiol Scand. 1997;160: ; Adapted from Nauck MA, et al. Diabetologia. 1996;39: ; Adapted from Drucker DJ. Diabetes. 1998;47:
33 GLP-1 stimulates b-cell regeneration and mass in animal models KeyRed arrows indicate effect of GLP-1b-cell neogenesisb-cellGLP-1 stimulates -cell regeneration and massStudies have demonstrated that GLP-1 plays an important role in maintaining -cells. In animal studies, GLP-1 increases -cell mass through the stimulation of -cell neogenesis, growth and proliferation. Proliferation results from differentiation and division of existing -cells, while neogenesis occurs through differentiation of insulin-secreting cells from precursor cells in the pancreatic ductal epithelium (Bulotta et al. 2002).Additionally, a recent study using freshly isolated human islets reported a reduction in the number of apoptotic -cells following 5 days of in vitro treatment with GLP-1 (Farilla et al. 2003). These observations of increased -cell mass and decreased apoptosis are of particular interest in the treatment of type 2 diabetes as progressive -cell dysfunction is one of the main pathophysiologies of the disease.ReferencesBulotta et al. J Mol Endocrinol 2002;29:347–360Farilla et al. Endocrinology 2003;144:5149–5158b-cell proliferationb-cell apoptosisb-cell hypertrophyb-cell regeneration and increased massFarilla et al. Endocrinology 2003;144:5149–5158. Bulotta et al. J Mol Endocrinol 2002;29:347–360.
34 Reduced GLP-1 secretion in type 2 diabetes 20GLP-1 (pM)*******15Normal10IGTT2D patientsMixed Meal560120180240Time (min)Source: Adapted from Toft-Nielsen et al. ( 2001): J Clin Endocrinol Metab 86:
36 Type 2 diabetes is NOT a mild disease StrokeDiabetic retinopathy1.2- to 1.8-fold increase in stroke3Leading causeof blindnessin working-ageadults1Cardiovascular disease75% diabetic patientsdie from CV events4DiabeticnephropathyDiabetic neuropathyLeading cause ofend-stage renal disease2Leading cause of non-traumatic lower extremity amputations51Fong DS, et al. Diabetes Care 2003;26 (Suppl. 1):S99–S102. 2Molitch ME, et al. Diabetes Care 2003;26 (Suppl. 1):S94–S98.3Kannel WB, et al. Am Heart J 1990;120:672–676. 4Gray RP & Yudkin JS. In Textbook of Diabetes 1997.5Mayfield JA, et al. Diabetes Care 2003;26 (Suppl. 1):S78–S79.
37 Serious complications of type 2 diabetes are present at diagnosis Retinopathy 21Abnormal ECG 18Absent foot pulses ( 2) and/or ischaemic feet 14Impaired reflexes and/or decreased vibration sense 7Angina 3Intermittent claudication 3Myocardial infarction 2Stroke/transient ischaemic attackPrevalence (%)**Some patients had more than one complication at time of diagnosisAdapted from UKPDS VIII. Diabetologia 1991;34:877–890.
38 Type 2 diabetes increases the risk of CVD Males with diabetesFemales with diabetesAny CV eventStrokeIntermittent claudication†Cardiac failure†CHD†‡MI‡Angina pectorisSudden death*N/ACoronary mortality††123456Age-adjusted risk ratio (1 = risk for individuals without diabetes)*P < 0.1; †P < 0.05; ‡P < 0.01; §P < 0.001Adapted from Kannel WB, et al. Am Heart J 1990;120:672–676.
39 Relative cost of diabetes 120$104100$9280$65Direct and indirect costs(US$ billion)60$4440$3020StrokeDepressionArthritisDiabetesCancerUS data from 1990–1993Adapted from Accessed 1 August, 2006.
40 Aggressive Glycemic Control in T2DM Reduces Risk of Complications Risk Reduction With 1% Decline in Updated HbA1cP <.0001P =.035P =.021P <.0001P <.000114%12%16%19%21%1537%43%30UKPDS 35: Risk Reduction in Diabetes-Related Complications(Updated HbA1c)[Note: be sure to include brief discussion linking this study with clinical data from UKPDS 33 (Lancet 1998; see p.409, 2nd column)]In the UKPDS, each 1% decrease in updated* HbA1c reduced the risk** of microvascular complications by 37%, peripheral vascular disease (PVD) by 43%, MI by 14%, stroke by 12%, heart failure by 16%, and cataract extraction by 19%, as shown on the slide. The investigators did not identify a cutoff point for HbA1c associated with the onset of risk for complications. Thus, a target value for HbA1c was not suggested, although the authors noted that HbA1c levels nearer to normal are obviously preferable.These data indicate that there is a quantitative relation between the risk of complications of diabetes and glycemia over time. The risk was shown to be lowest in patients with HbA1c concentrations <6%.*Updated = HbA1c measured over time as an updated mean of annual measurements.**As assessed by Cox regression models. Potential confounding risk factors included in all Cox models were sex, age, ethnic group, smoking (current/ever/never) at time of diagnosis of diabetes, and baseline HDL-C and LDL-C, triglyceride, presence of albuminuria ( > 50 mg/L measured in a single morning urine sample) measured after 3 months‘dietary treatment, and systolic blood pressure represented by the mean of measures at 2 and 9 months after diagnosis.Stratton IM et al. BMJ. 2000;321:45Micro-vascular diseasePVD*MIStrokeHeart failureCataract extractionDeath related to diabetesPVD = Peripheral Vascular Disease; MI = Myocardial Infarction*UKPDS 35: Prospective observational analysis of UKPDS patients (n = 4585, incidence analysis; n = 3642, relative risk analysis). Median 10.0 years of follow up.Adapted from Stratton IM, et al. BMJ. 2000;321:
41 Absolute cost savings associated with improved glycaemic control Mean reduction in diabetes-related costs for improved vs. unimproved type 2 diabetes patients1994199519961997–100–200–300–400–500Cost per patient per year ($US)–600–700–$685–800–$772–$821–900–1000–$950Patients whose HbA1c decreased 1% between 1992 and 1993and sustained the decline through 1994 were considered to be improved (n = 732); all others were classified as unimproved (n = 4,012)Adapted from Wagner EH, et al. JAMA 2001;285:182–189.
43 < 6.0%* (individual goal) Current Treatment Goals for Glycemic Control: Towards Reducing Risk of ComplicationsADAACEIDFHbA1c< 6.0%* (individual goal)< 7.0%* (general goal)≤ 6.5%†< 6.5%*Preprandial capillary plasma glucose90–130 mg/dL(5.0–7.2 mmol/L)< 110 mg/dL(< 6.0 mmol/L)Peak postprandial capillary plasma glucose‡< 180 mg/dL(< 10.0 mmol/L)< 140 mg/dL(< 7.7 mmol/L)< 145 mg/dL(< 8.0 mmol/L)ADA = American Diabetes Association; ACE = American College of Endocrinology; IDF = International Diabetes Federation*Referenced to a non-diabetic range of 4.0%–6.0% using a DCCT-based assay; †Upper limit of normal = 6.0%‡Measurements should be made 1–2 hours after the beginning of the mealAdapted from American Diabetes Association. Diabetes Care. 2005;28(supp 1):S4-S36. International Diabetes Federation. Global Guideline for Type 2 Diabetes. Brussels: International Diabetes Federation, American Association of Clinical Endocrinologists and the American College of Endocrinology. Endocrine Practice. 2002;8(suppl 1): 5-11.
44 Two Thirds of People with Type 2 Diabetes are Not at Goal1 HbA1c Level% Patients<7.0%37.07.0%–8.0%25.8>8.0%37.2>9.0%20.2>10.0%12.41NHANES 1999–2000 DataT2DM represents ~90%–95% of casesAdapted from Adapted from Saydah SH, et al. JAMA. 2004;291:
45 6.2% – upper limit of normal range UKPDS: type 2 diabetes is progressively worsening independently on current therapies9Conventional*GlibenclamideChlorpropamideMetformin8InsulinMedian HbA1c (%)UKPDS clearly showed the need for new diabetes treatmentsIn UKPDS, the yearly median HbA1c in patients receiving conventional treatment increased steadily throughout the trial. Indeed, within 2 years of diagnosis, this group had a median HbA1c above the recommended target level of < 7.0%. In contrast, median HbA1c fell during the first year in patients receiving intensive treatment (glibenclamide, chloropropamide, metformin or insulin) but gradually increased subsequently and only remained within the recommended treatment target for the first 3–6 years of treatment (depending on assigned treatment). During the remaining years of follow-up, median HbA1c continued to rise steadily above treatment targets. This failure of existing treatments, even when used intensively in highly motivated patients highlights the need for new treatments in the management of type 2 diabetes.UKPDS methodologyUKPDS recruited 5102 patients with newly diagnosed type 2 diabetes.Conventional therapy aimed to maintain fasting plasma glucose (FPG) at < 15 mmol/l (270 mg/dl) using diet alone initially. However, sulphonylureas, insulin or metformin could be added if target FPG was not met.Patients assigned to intensive therapy had a target FPG < 6 mmol/l (108 mg/dl) and, in insulin-treated patients, a pre-meal FPG of 4–7 mmol/l (72–126 mg/dl). Non-overweight patients were randomised to insulin or sulphonylurea monotherapy initially. Overweight patients receiving intensive treatment could also be randomised to metformin. These agents could be combined if necessary to maintain target FPG during the trial.The data in this figure are from overweight patients (UKPDS 34). The HbA1c findings in non-overweight patients were similar; regardless of treatment, median HbA1c exceeded the recommended treatment targets within 8 years of therapy (UKPDS 33).ReferencesUKPDS 34. Lancet 1998;352:854–865UKPDS 33. Lancet 1998;352:837–8537Recommended treatment target ≤ 7.0†66.2% – upper limit of normal range246810Years from randomisationAdapted from: UKPDS 34. Lancet 1998:352:854–865. *Using diet initially then sulphonylureas, insulin and/or metformin if FPG > 15 mmol/l; †ADA clinical practice recommendations. n=5102
46 Determinants of type 2 diabetes and anti-diabetic agents Insulin resistance Metformin, TZDs, insulinLoss of b-cell functionGlucotoxicity Any anti-diabeticLipotoxicity Any anti-diabeticSecretory defects Sulfonylureas, Glinides, insulinInflammation TZDs (mild), anti-IL1b (exp)Islet amyloid deposition None (?TZDs)Incretin failure Incretin mimetics, analogues, DPP-4 inhibitorsalpha-cell dysfunction Idem, insulin
47 Major Adverse Events of Current Treatments for T2DM Limit Efficacy MetforminGI effects (nausea, diarrhea), lactic acidosis (rare)SUsHypoglycemia, weight gain, hyperinsulinemia*GlinidesTZDsWeight gain, edema, fractures, ?CHFα-Glucosidase inhibitorsGI effects (flatulence, diarrhea)Incretin mimetics (injection)GI effects (nausea, vomiting, diarrhea)
48 Standard Approach to the Management of T2DM: Treatment Intensification Lifestyle ChangesInsulinOral + Insulin+Oral Combination+Oral MonotherapyDiet and Exercise
49 Historical Algorithm of Therapy for Type 2 Diabetes Inadequate nonpharmacologic therapyOral agent2 Oral agents3 Oral agentsIt has been common practice to reserve insulin therapy until relatively late in the treatment plan for patients with type 2 diabetes. Typically, it is introduced after patients have failed to achieve glycaemic control with diet and with combination therapy using 2 or 3 oral hypoglycaemic agents of escalating dosages1,2Based on the time associated with various oral agent alterations (eg, titration and combination therapy), patients are often out of control for lengthy periods and thus increase the risk of complications related to chronic hyperglycaemia1Add insulinAdapted from Mudaliar S et al. In: Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY: Appleton and Lange; 2003:1. Mudaliar S, Henry R. The oral antidiabetic agents. In: Porte D, Jr, Sherwin RS, Baron A. Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY: Appleton and Lange; 2003:2. Riddle MC. Tactics for type II diabetes. Endocrinol Metab Clin North Am. 1997;26:
50 Possible Alternative Algorithm of Therapy for Type 2 Diabetes Inadequate nonpharmacologic therapySevere symptomsSevere hyperglycaemiaKetosisPregnancyOral agent2 Oral agents3 Oral agentsClinicians may consider this proposed algorithm for the treatment of patients with type 2 diabetes. In this algorithm, insulin can be integrated into a patient’s regimen at various stages of the diseaseAdd Insulin Earlier in the Algorithm
51 Beta-cell function (%) Approximate time (years) The Number of Medications Taken Usually Increases With Duration of DiseaseDiabetes diagnosedMonotherapyfailureRequiring insulin10080MonotherapyDual-drugregimensMultidrugcomboinsulinInsulin-basedregimens60Beta-cell function (%)40IGT201015–25Approximate time (years)IGT=impaired glucose tolerance.UKPDS 16. Diabetes. 1995;44:1249–1258.Turner RC et al. JAMA. 1999;281:2005–2012; Warren RE. Diabetes Res Clin Pract. 2004;65:S3–S8; Lebovitz HE. Med Clin N Am. 2004;88:847–863.
53 Management of Hyperglycemia in Type 2 Diabetes: ADA/EASD Consensus Algorithm for the Initiation and Adjustment of TherapyDiagnosisStep 1Lifestyle Intervention + MetforminNoYes*A1C≥7%Add Basal Insulin#(most effective)Add Sulfonylurea(least expensive)Add Glitazone(no hypoglycemia)Step 2NoYes*A1C≥7%Intensify Insulin#Add GlitazoneAdd Basal Insulin#Add SulfonylureaStep 3Add Basal or Intensify Insulin#Intensive Insulin + Metformin ± GlitazoneNoYes*A1C≥7%Nathan DM et al, Diabetes Care, 2006; Diabetologia 2006
54 Nel DMT2 sono elevati sia i livelli di glicemia a digiuno sia i post-prandiali Diabete non controllato (HbA1c ~8%)300Iperglicemiapost-prandiale:HbA1c ~+1%200Iperglicemia aDigiuno:HbA1c ~+2%Glicemia plasmatica (mg/dl)100HbA1c normale~5%Nei soggetti con DMT2 sia i livelli di glicemia a digiuno che post-prandiali sono significativamente più elevati rispetto ai soggetti sani.In un soggetto con HbA1c di 8%, circa il 2% è determinato dall’ipeglicemia a digiuno (basale) e un ulteriore 1% e determinato dall’iperglicemia post-prandialeL’iperglicemia a digiuno è determinata da un’eccessiva produzione epatica di glucosioRiddle M. Diabetes Care 1990;13:676–86.DeFronzo R. Diabetes 1988;37:667–87.CPC06.0012.0018.0024.0006.00Momenti della giornata (ore)C=colazione; P=pranzo; C=cena.Adapted from Riddle M. Diabetes Care 1990;13:67686.
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