MEDICAL GUIDELINES FOR CLINICAL PRACTICE FOR THE MANAGEMENT OF DIABETES MELLITUS: AACE Diabetes Mellitus Clinical Practice Guidelines Task Force Chairperson Helena W: Rodbard, MD. FACP, MACE Medial Breen Eadocrae and Stabe Cosette Past Besdent Arenan Atsocaton of Cineal Endontacloins ‘ast Pendent Aumneas Cllege of Endocnaclons Rocsale Misiaad Tash Force Members Lawrence Blonde, MD, FACP, FACE ‘Duet, Ochuet Dahees Chae Reartes Un, Secaoa ob Ealocsaolop. Dabeies, and Metabole Duseses ‘Asn Resdencs Progra Duectoc Deparaeat of ateal Meatase Nev Orlesss Lousiana | Susan S. Braithwaite, MD, FACP, FACE. | | | AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS (CuealPfertorof Medicine Caer of Non Calis Disioa of Endocrnaloge, Chapel ill, NC Elise M. Brest, MD, FACE Asstt Case Poser of Medico: Doon of Egonga sd Boe Diss: Moar Sa Scho of Medne ‘New You New Your Rhoda H. Cobia, MD, MACE. ‘Cimal Professor of Medicine: Dvsin of Endoensology, Deis and Bone Dueste: Monat Siam Sebool of Medicine "dure Past Predeat Aserecan Collegeof Eatocciony ast Presiden, Asmencan Arsoctaton of Cinseal Endoensolopns, New Vouk, New York Yehuda Handelsman, MD. FACP, FACE Medical Duecor Metab Insite of Aenea ‘Ser Sonic Constant Metabo Endorse Elucios Fontan, Tarzana Calera | Richard Hellman, MD, FACP. FACE (Clineat Pofessr of Medion, Uaneruty of Missoun-Kanea Cay Sebo! of Mediete President Amencan Assocation of Chines! Endocnaolopts Nor Kansas Con Miso | Paul S. Jellinger, MD, MACE | Professor of Mediese and Voluntary Fac Unser of Mama Scho! of Med, Dist Pendent, Ameneas Collegeof Eodocnslog® Past resem, Amoncia Associaton of Chase! Eadosncloasts, Hollywood, Floats Lois G. Jovanovic, MD, FACE (CEO & ChuetScistSc Ofc Sancum Duetes Resexeh Isnt Ade Profesce Biomaieculss Science sad Engines, nets of Calon: Saat Barbar Chea! Professor of Mediie, Universite of Somer Califor Keck School of Medicine Saat Barbara, CA Philip Levs, MD. FACE ‘Cleat Piofeetor af Medi, Umer of Anzona Collegeof Medicine aot Prendem American Collegeof Endoclps. Phoeni, Jeffrey I. Mechaniek, MD, FACP, FACE. FACN AssonteCacl Professor of Medicine and Duct of Metabolic Suppet Dain of Eadacologs ‘Dabcks ad Boor Dsesse Mont Snas Schaal cf Medica New Yaak New Va Farhad Zangeuch, MD, FACP, FACE Assstnt Cael Professor of Medsesne, Grenge Watansioa Uaiteuty Scho of Mediee, Washugton, DC “Endocrae, Diabetes and Osteoporons Clinic (DOC), Stein, Visas Medical Writer Christopher G. Parkin, MS Reviewers Lense E Braverman, MD, Saamel Darge'lacl MD, FACE, Vian A Fonseca MD. FACE. Maa M.Geajover MD, ACP. FACE Vugasa A LiVols MID. Feige Ovale MD FACE Herbert Resuager MD. FACE. Tala P Shank MD. FACE Joseph J Toue, MD. FACP.FACE, Dace L Tieace, MD. FACE Acknowledgments We wont ike secognze Elbo Seth. MD, FACE, ad Josep Vassalts, MD, for thew review ofthese guidelines ud hous comments ENDOCRINE PRACTICE Vol 13 (Suppl 1) May/June 2007Table 2.1. Risk Factors for Prediabetes and Diabetes Mellitus (1) Risk Factors Family history of diabetes Cardiovascular disease Overweight or obese state Sedentary lifestyle Latino/Hispanic, Non-Hispanic black, Asian American, Native American, or Pacific Islander ethnicity Previously identified impaired glucose tolerance or impaired fasting glucose Hypertension Increased levels of triglycerides, low concentrations of high-density lipoprotein cholesterol, or both History of gestational diabetes History of delivery of an infant with a birth weight >9 pounds Polycystic ovary syndrome Psychiatric illness ‘Table 2.2. Clinical Interpretations of Plasma Glucose Concentrations (2) Glucose Concentration, mg/dL. Clinical Interpretation Fasti <100 Within the reference range 100-125, Impaired fasting glucose/prediabetes mellitus 2126 Overt diabetes mellitus 2-hour postchallenge load (7: oral glucose tolerance test) <140 Within the reference range 140-199 Impaired glucose tolerance/prediabetes mellitus 2200 Overt diabetes mellitusAACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13{Suppl 1) 2007 11 Diagnostic Criteria for Diabetes Mellitus* (3) Diagnostic C Symtoms of dae (pla, polish. usexpained weight Fos) ps casual plasma goose concentration 2200 me Fasting plasma slucose concentration =126 me/dL 2-hour postchallenge glucose concentration 2200 mg/dL during a 75-¢ oral slucose tolerance test One ofthe 3 criteria listed is suficient ro establish the diagaosis of diabetes mills, These assessanente should be confirmed by repeated testing on a subsequent day inthe absence of unequivocal hyperglvcemia. Table 2.4. Risk Factors for Gestational Diabetes Mellitus Risk Factors >25 years of age Overweight or obese state Family history of diabetes mellitus (e, ina first depree relative) History of abnormal slucose metabolism History of poor obstetric outcome History of delivery of an infant with a birth weight >9 pounds History of polycystic ovary syndrome Latino/Hispanic, non-Hispanic black, Asian American, Native American, or Pacific Islander ethnicity Fasting (no energy intake for at least 8 hours) plasma glucose concentration >85 mg/dl or 2-hour postprandial elucose concentration >140 mg/dl. indicates need to perform a 75-2 oral cose tolerance tes) (4,5) Diagnostic Criteria for Gestational Diabetes Mellitus Using a 78-g Oral Glucose Tolerance Test*2) =e Plasma Glucose Concentration, State at Plasma Glucose Measurement mgadL Fasting 295 [hour postglucose administration S180 hour postelucose administration 3155 "Two or more of the listed venous plasma glucose concentrations must be met or exceeded for a positive diagnosis. The test should be performed after an overnight fas of 8 t0 14 hours and afer at east 3 days of tanesticted dit (ie, 22150 p earbohydeate per day) and ualinited physical aeviy12 AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13{Suppl 1) 2007 ‘Type 1 Diabetes Mellitus Accounts for only 5% to 10% of all diabetes mellitus cases Caused by an absotute deficiency of insulin secretion due to a cellular-mediated autoimmune destruction ‘of the pancreatic B-cells Viruses associated with initiation of B-cell destruction include congenital rubella, coxsackievirus B. cytomegalovirus, adenovirus, and mumps Markers of -cell destruction include islet cell autoantibodies, autoantibodies to insulin, autoantibodies stamic acid decarboxylase (GAD6S), and autoantibodies to the tyrosine phosphatases IA-2 and Rate of f-cell destruction varies —infants and children often experience rapid cell destruction; rate of destruction is usually slower in adults Individuals at increased risk can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islet cells and by genetic markers ‘Type 2 Diabetes Mellitus Accounts for 90% 10 95% of all diabetes mellitus cases Caused by a combination of complex metabolic disorders that result from coexisting defects of multiple ‘organ sites such as insulin resistance in muscle and adipose tissue. a progressive decline in pancreatic insulin secretion, unrestrained hepatic glucose production, and other hormonal deficiencies Before the appearance of clinical symptoms, a degree of hyperglycemia may be present, causing pathologic and functional changes in various target tissues ‘Most affected individuals are obese and, therefore, have variable degrees of insulin resistance; affected individuals who are not obese may have an increased percentage of visceral fat, which can cause insulin resistance Other risk factors include increasing age and sedentary lifestyle ‘Occurs more frequently in women with previous gestational diabetes and in individuals with hypertension or dyslipidemia Associated with a strong genetic predisposition Gestational Diabetes Mellitus Defined as any degree of glucose intolerance identified during preenancy: definition applies regardless of the therapy used to treat the condition“ons nonsefer ‘unt O6-0F (eupidy) wonoatur ouisTNTs Ws> UH O6-OF Gopeump) wonsetar ardsy wasup Ws> unt O6-0F nsuy e-prdley SoeRTT Tp sant Sy] Pana, Zh 2002 (1 Iddns)er:200z 72e4g 420pUz (2) suopesudorg, ‘sou! wid “Tp UL,AACE Diabetes Mellitus Guidelines, Endocr Pract. 2007;13(Suppl 1) 2007 19 ‘Table 4.2. Examples of Pharmacologic Regimens for Treating Type 2 Diabetes Mellitus* [ Patients With Type 2 Diabetes Mellitus Naive to Pharmacologic Therapy i: Initiate monotherapy when HDA,, levels are 6%-7% Options include: Metformin (5.6) | Thiazolidinediones (7.8) | Secretazogues (9-12) Dipeptidyl-peptidase 4 inhibitors (13) ‘-Glucosidase inhibitors (14.15) | Monitor and titrate medication for 2-3 months. | Consider combination therapy if glycemic goals are not met at the end of 2-3 months Initiate combination therapy when HDA, levels are 7%-8% Options include: Seeretagozue + metformin (16,17) Secretagogve + thiazolidinedione (18,19) Secretazogue + c-slucosidase inhibitor (20) ‘Thiazolidinedione + metformin (21,22) Dipeptidyl- peptidase 4 inhibitor + metformin (23) Dipeptidyl-peptidase 4 inhibitor + thiazolidinedione (23) Seeretazogve + metformin + thiazolidinedione (24,25) Fixed-dose (single pill) therapy ‘Thiazolidinedione (pioglitazone) + metformin (26) ‘Thiazolidinedione (rosiglitazone) + metformin (27) ‘Thiazolidinedione (rosiglitazone) + secretagozve (elimepiride) (28) Thiazolidinedione (pioglitazone) + secretagogue (slimepiride) (29) Seeretagozue (glyburide) + metformin (30) Rapid-acting insulin analogs or premixed insulin analogs may be used in special situations (31) Inhaled insulin may be used as monotherapy or in combination with oral agents and long-acting insulin analogs Insulin-oral medications: all oral medications may be used in combination with insulin; therapy combinations should be selected based on the patient's self-monitoring of blood glucose profiles Initiate/imensify combination therapy using options listed above when HDA,, levels are 8%-10% to address fasting ‘and postprandial glucose levels, jate/intensify insulin therapy when HbA, levels are >10% Options include: Rapid-acting insulin analog or inhaled insulin with long-acting insulin analog or NPH (32.53) Premixed insulin analogs (31,34) Patients with Type 2 Diabetes Mellitus Currently Treated Pharmacologically ‘The therapeutic options for combination therapy listed for patients naive to therapy are appropriate for patients being treated pharmacologically Exenatide may be combined with oral therapy in patients who have not achieved glycemic goals, Approved exenatide + oral combinations: Exenatide + secretazozue (sulfonylurea) (36) Exenatide + metformin (37) Exenatide + secretagogue (sulfonylurea) + metformin (38) Exenatide + thiazolidinedione Pramlintide may be used in combination with prandial insulin, ‘Add insulin therapy in patients on maximum combination therapy (oral-oral.oral-exenatide) whose HDA, levels are 65%-8:5% 33) Consider initiating basal-bolus insulin therapy for patients with HbA, levels >8.5% Abbreviations: HbA, hemoglobin A: NPH, neutral protamine Hagedorn "The options listed afin no order of reference.‘aevasip [euar aroA3s apes sitaned 103 paptatintoray ION, seat (iis gaxstUpy poos mnomEn 10 IEW sosrERUPY. 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Considerations for Oral Therapy in Patients ‘Type 2 Diabetes Mellitus (83) Prima Possible Adverse Drug Class Mechanisms Effects Monitoring? Comments | Sulfoaslureas | Stimulates ineulin | Hypoglycemia Fasting plasma ‘Response plateaus afer half lense Waaght gain shucose at? ‘axinnim dose weeks Glipitide and glimepizide HbA, 3¢ 3 mouthe ‘may be preferred in eldedy patients Biguanides hibits hepatic | Dose-elated ‘Serum creatinine at | Less associated weight gain ‘lucoue oupet iambea (osually | initiation than wich eulfonslureas and selfimiting in| Fasting plasma thiazolidisediones: weight 7.10 days) slocose at 2 Joss may oseur: helps Limit Lactie acidosis in eck ‘weight gain in combinatioa therapy patients with HuA,.a13 mouths | Mazinum effective dorage is 2 g/d | reoal Contrsindications | compromise | Seruas creatinine >1.5 | ‘mg/d (men). >1-4 mg/d (women) | Congestive bear faire ‘drug therapy Hepatic disease Aleohol abuse @Ghocesidase | Delays Dose-relaed PPG 3 inidarion “Administer with fist bite of Inhibitors carbohydrate aches, HA), at 3 months each meal absorption to abdonical pain, Use slow titration to avoid ecreace Aarleace ‘pastointerinal adverse effects postprandial ly for ? weeks Byperplycemia then 25 rove daily for 2 weeks: then 25 mg three times daly for 8 ‘weeks: maximum dosage is 100 mg three times daily) Must use glucose if hhypogltcemia occurs Thiazolidine- | Eshances insulin | Edema AST and ALT s | Decrease in glicose may not Sionee sensitiviny Weight gain baseline bbe apparent for 4 weeks Congestive heat | Monitor for signs of | Maninnam efficacy of dore may not be | failure aid overload observed for +6 moaths Contrsindicstions: | CALT>2.5 times the upper lint of normal Hepatic disease [Alcohol abuse NYHA clate Il or IV Glinides ‘Simulates insulin | Hypoglycemia Fasting plasma ‘Commonly used for basal ‘eration ‘glucose at 2 weeks | bolus dosing schedules HBA,, 303 mouthe PPG lt initiation DPP-STalubivers | Restores GLP.1 | Not clinially PG at initiation Reduce dosage in pateats and GIP levels ipificant Fasting plasma with renal insufficiency ‘plucose at 2 weeks | No weight gain or markedly HBA), at 3 mouths ‘reduced incidence of hypoglycemia Abbeeviation: ALT, alanise minotransferase; AST, aspartate aminotrasferase: DPP-tinubitors,dipeptids-pepidase $inubitors GIP, glove ‘epeadent instinouopre polypeptide, GLP. glucagon-like pepude 1, HLA, hewoalobsa A, PPG, postprandial slucon, NYHA, New York Heat ‘Atsociation cardiac diate sd fuoctonl capacity ‘all measueceass should be perfoned atte tine aoted afer station of therapy and theceafies ae diceted bythe patente physician,auozentaord + sonqnqur p osepnded-jApndadig UrULOF|euI + TONGnyur p asepndad-[Apndadiq unUIOpaut + suOzI|SISON uO + SuOZTTIONG unuopatt + spruypsedoy ‘asoqawoe + vamjAuos[ng auozenaord + vamyauogjng SuOTEN|TISor + vaMjAUOSTNS TtOpaT + eaMpxUOFING deroyL woREUTquto; Cr) 60 38'0 apneuexg (6) 95°0 OF EVO epnururerg Sojquisaluy wyASUNTON, (<2) 80 srouqnyut p esepyded-jApndodiq (OPT LS) £1990 SIOWQNUT SSLPISOoNTH-D CFS IT UST ‘SauOIpaurpHozenyL, @sssopoeNTT | Cammopjami) aprrensig_ | @S01D Sz 60 svamyAuoging Advsatpouoyy % ‘wononpay Ty urqopzourayy Advasoyy 30.1q SMUTPIA S2OqUIG WIAA SwAHEY UT sjasoT *ly urqo]Zourayy uo sarduaayy [8.1Q Jo 9aJJq “9p FIQUL 24% L002 (t Iddng)¢e4!200% 39e4g 420pUZ ‘seuyepiny snweW Se¥eqer gov