Rev Panam Salud Publica 28(6), 2010 463

Treatment of type 2 diabetes in Latin America:a consensus statement by the medicalassociations of 17 Latin American countriesJuan Rosas Guzmn,1 Ruy Lyra,2 Carlos A. Aguilar-Salinas,3Saulo Cavalcanti,4 Felix Escao,5 Marcos Tambasia,6Elizabeth Duarte,7 and the ALAD Consensus Group1

Latin America faces unique challenges in the treatment of type 2 diabetes mellitus. The Aso-ciacin Latinoamericana de Diabetes (Latin American Diabetes Association, ALAD) broughttogether medical associations in 17 countries in Latin America to produce a consensus state-ment regarding the treatment of type 2 diabetes. The goal of the document is to provide prac-tical recommendations that will guide clinicians through a simple decision-making process formanaging patients. The cornerstone elements for therapeutic decision making are: severity ofhyperglycemia, clinical condition of the patient (stable or with metabolic decompensation), andbody mass index. The consensus includes a section devoted specifically to patients with obe-sity. Information is presented as highly-relevant clinical questions. The algorithm is based onthe scientific recommendations of the 2006 ALAD guidelines (a document prepared using anevidence-based approach) and data from recent randomized controlled studies.

Diabetes mellitus, type 2; obesity; consensus; practice guidelines as topic; Latin America.

ABSTRACT

Latin America is undergoing a re-markable epidemiological transforma-tion. Diabetes and other chronic, non-transmissible diseases are now theleading health problems. Despite the

large and growing number of diabetescases, this geographic area invests limitedfinancial resources in diabetes care. In-deed, diabetes prevalence in several LatinAmerican countries is among the highestin the world, e.g., Mexico at 14.4% (1). Inthe year 2000, the direct cost of diabetescare in Latin America and the Caribbeanwas approximately US$ 10 billion; mini-mal when compared to the indirect cost of about US$ 55 billion resulting fromdisease-related consequences. In 2000, the total diabetes-related annual cost inLatin America and the Caribbean wasUS$ 65 billionUS$ 15 billion in Mexico, US$ 2.6 billion in Central America, andUS$ 44.4 billion in South America.

In Latin America, families pay about40%60% of diabetes costs out-of-pocket.Most private health insurance planscover medical assistance, procedures,and hospitalization, but not medication(25). The burden of disease will be evengreater in the coming years because thepopulation has a large proportion ofyoung adults living in urban areas andengaged in unhealthy lifestyles. Thus,the impact of diabetes in Latin Americais growing fast and the national healthsystems are unprepared.

Latin America urgently needs to reor-ganize its health care services from a sys-tem designed to treat acute infectiousdisorders to one focused on behavior

Key words

Informe especial / Special report

Guzmn JR, Lyra R, Aguilar-Salinas CA, Cavalcanti S, Escao F, Tambasia M, et al. Treatment of type2 diabetes in Latin America: a consensus statement by the medical associations of 17 Latin Americancountries. Rev Panam Salud Publica. 2010;28(6):46371.

Suggested citation

1 Asociacin Latinoamericana de Diabetes, Celaya,Guanajuato, Mxico.

2 Federacin Panamericana de Endocrinologia, Per-nambuco, Brazil.

3 Sociedad Mexicana de Nutricin y Endocrinologa.Mxico City, Mexico. Send correspondence to CarlosAlberto Aguilar-Salinas, caguilarsalinas@yahoo.com.

4 Sociedade Brasileira de Diabetes, So Paulo, Brazil.5 Sociedad Dominicana de Endocrinologa, Santo

Domingo, Repblica Dominicana. 6 Sociedade Brasileira de Endocrinologia e Metabo-

logia, Rio de Janeiro, Brazil.7 Sociedad Boliviana de Endocrinologa, Metabo-

lismo y Nutricin, La Paz, Bolivia.

modification, long-term treatment ad-herence, and achievement of therapeuticgoals. Such restructuring should bebased on the best available clinical evi-dence, but existing international guide-lines should be adapted to reflect the dif-ferences and needs of each geographicarea. The unique challenges regardingtype 2 diabetes treatment in Latin Amer-ica are a result of the interactions amongthe areas socioeconomic factors, its vari-ety of cultures and traditions, and itslimited health resources. Consensus doc-uments and practice guidelines that arespecifically oriented toward the LatinAmerican environment are needed totrain and guide primary care physicians.

CONSENSUS METHODOLOGY

The Asociacin Latinoamericana deDiabetes (the Latin American DiabetesAssociation, ALAD) is committed tomedical education throughout LatinAmerica. In line with its commission,ALAD called upon leaders and represen-tatives from the endocrine and diabetesassociations of 17 countries in LatinAmerica to produce a consensus state-ment for the treatment of type 2 diabetesmellitus.

Participants received background in-formation prior to a face-to-face meeting.The participants were divided into threegroups; each group discussed and re-sponded to three of the nine questionsaddressed by the present report. Conclu-sions were presented by each group tothe audience, made up of the other twogroups; each recommendation was dis-cussed until unanimous agreement wasreached. A writing committee preparedthe summary, which was approved byall of the endorsing associations repre-sentatives. The final version of the docu-ment was prepared and approved by themembers of the writing committee.

The aim of the meeting was to createfeasible recommendations that could beput into practice quickly by the partici-pating countries. The algorithm wasbased on the scientific recommendationsof the 2006 ALAD guidelinesa docu-ment prepared using an evidence-basedapproach (6)and data from recent ran-domized controlled studies. The princi-pal conclusions of the document (e.g.,treatment goals) are in accordance withthe recommendations of the AmericanDiabetes Association of the United Statesof America.

CONSENSUS STRUCTURE

An algorithm to guide the treatment ofhyperglycemia was constructed thattakes into account the glycemic status ofthe patient. Special emphasis was placedon the most common clinical situations.Also included in this algorithm were thepossible clinical scenarios diabetes pa-tients may present and the necessary ac-tions to follow in each case. Addition-ally, two groups of patientsdividedaccording to the level of glycemic controland clinical conditionare included:

Group 1. Patients with blood glu-cose levels < 240 mg/dL (13.3 mmol/L),HbA1c < 9%, and clinically stable.

Group 2. Patients with blood glu-cose levels 240 mg/dL (13.3 mmol/L),HbA1c 9, and:

a. with few symptoms, no ketosis.b. catabolicsymptomatic, weight

loss, and ketosis-prone.

The cornerstone elements for ther-apeutic decision-making presented inthis document are: severity of hyper-glycemia, the clinical condition of thepatient (stable or with metabolic decom-pensation), and body mass index (BMI).The Consensus includes a section specif-ically aimed at patients with obesity.These patients constitute a therapeuticchallenge; primary care units do nothave the resources to manage such cases.Without a multidisciplinary approachand adequately informed medical per-sonnel, patients, and relatives, obese pa-tients with diabetes frequently continuegaining weight and do not achieve treat-ment goals. Counseling for behaviormodification is fundamental in thesecases. The section on obesity emphasizesthe importance of helping patients fol-low a healthy lifestyle before and duringthe escalation of pharmacological treat-ment. It is hoped that this resource bemade available in every primary carecenter.

THE CONSENSUS STATEMENT

The clinical recommendations for treat-ment of type 2 diabetes in Latin Americaare presented as clinical questions:

1. What are the treatment goals for thepatient with type 2 diabetes?Glycemic control is fundamental to

the management of diabetes. In type 2diabetes, the Kumamoto study (7)

and the United Kingdom ProspectiveDiabetes Study (UKPDS) (8, 9) demon-strated significant reductions in mi-crovascular and neuropathic complica-tions with intensive therapy. Similar tothe Diabetes Control and ComplicationsTrialEpidemiology of Diabetes Inter-ventions and Complications (DCCT-EDIC) studies findings (10), long-termfollow-up of the UKPDS cohort has re-cently demonstrated a legacy effect ofearly, intensive glycemic control onlong-term rates of microvascular compli-cations. This benefit continues, even ifthe differences in glycemic control be-tween the intensive and standard co-horts are lost after the end of the study(10, 11). In Latin America, fasting bloodglucose (venous or capillary) values arethe key elements used by physicians toevaluate their patients and guide deci-sions. However, in line with other scien-tific organizations (1214), glycosylatedhemoglobin (HbA1c) is recommended asthe optimal method to assess glycemiccontrol. As shown in Table 1, A1c levelscan be translated to mean plasma glu-cose concentrations, making it easier forpatients to understand the information.In several large, randomized, prospec-tive clinical trials, treatment regimensthat reduced A1C < 7% were associatedwith fewer long-term microvascularcomplications. Whereas many studiesand meta-analyses (1517) have shown adirect relationship between A1C and theincidence of cardiovascular events, thepotential of intensive glycemic control toreduce cardiovascular mortality hasbeen less clearly defined. Based on cur-rent clinical evidence (1821), an HbA1c< 7% is recommended as the most ap-propriate level for the majority of pa-tients. However, in certain situations thisobjective must be customized. For exam-ple, in young patients with no evidenceof complications and no major risk of hy-

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TABLE 1. Relationship between blood glucoselevels and Hemoglobin A1c (HbA1c)

Mean blood glucose levels HbA1cmg/dL mmol/L (%)345 19.5 12310 17.5 11275 15.5 10240 13.5 9205 11.5 8170 9.5 7135 7.5 6

poglycemia, an HbA1c value < 6.5% maybe considered.

In addition, this Consensus highlightsplasma lipid and blood pressure goals asprominent objectives of diabetes man-

agement (Table 2). Several controlledstudies and meta-analyses have shownthe benefits of lipid lowering therapiesin patients with diabetes. The same istrue for antihypertensive therapy. The

review of the supporting evidence is be-yond the scope of this document.

Finally, the panel recommended theinclusion of microalbuminuria as a treat-ment target. The concentration of mi-croalbuminuria should be measured an-nually in all type 2 diabetes patients andin type 1 diabetes patients with diseaseduration 5 years. Microalbuminuriashould be treated by achieving bloodpressure targets; the use of angiotensin-converting enzyme (ACE) inhibitors in-hibitors and angiotensin II receptorblockers have been shown to delay theprogression to macroalbuminuria.

Figure 1 demonstrates the modifica-tions advocated for ALADs 2006 type 2diabetes mellitus treatment algorithm(6). Non-pharmacological recommenda-tions are summarized in Table 3. Drugscurrently used in diabetic care, includingmean and maximum doses are described

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TABLE 2. Proposed treatment goals for patients with type 2 diabetes in Latin America, 2010

Parameter Targets Unit

Fasting blood glucose 70120 mg/dL (3.8 6.6 mmol/L)2-hour post-prandial glucose < 140 mg/dL (7.7 mmol/L)Hemoglobin A1C < 7 %LDLa cholesterol < 100 m/dL (2.6 mmol/L)

< 70b mg/dl (1.8 mmol/l) HDLc cholesterol (both genders) > 40 mg/dL (1.05 mmol/L)Triglycerides < 150 mg/dL (1.68 mmol/L)Microalbuminuria < 30 mcg/g creatinine (spot sample)

< 30 mg/day (24-hour urine sample)Blood pressure 130/80 mm/HgBody mass index > 19 < 25 kg/m2

aLow density lipoproteins.bWith cardiovascular disease or at high risk (defined as the presence of one or more cardiovascular risk factors).c High density lipoproteins.

FIGURE 1. Latin American Diabetes Association recommendations for the management of hyperglycemia in patients with type 2 diabetes, 2010

Start lifestyle change (LSC) + Metformin (MET)If MET is contraindicated, or not tolerated, consider any of the following antidiabetic medications: tiazolidinedione (TZD), DPP-4 inhibitors (DPP-4 INH), sulfonylurea (SU) (especially if body mass index (BMI) < 27 kg/m2), meglitinides (especially in presence of high postprandial blood glucose), acarbose (if postprandial blood glucose is high, but fasting glucose is < 180mg/dL and/or HbA1c < 7.5%)

ObeseIncrease weight controlUncontrolled

Clinically stable with no ketoacidosis

Clinically unstableProne to ketoacidosisWeight loss

HbA1c 9%

HbA1c 7 a < 9%

Reinforce lifestyleMET at maximum dose

Adjust dose and reassess therapy

Good controlWeight increaseProne to hypoglycemia episodes

UncontrollabilityWeight loss

Add insulin:NPH (1 nightly dose), orGlargine (1 dose, sometimes 2) or Detemir (12 doses daily)

LSC + Insulina

NPH once or twice dailyPremixed twice daily

Glargine or Determir 12 doses daily, usually combined with oral drugs or with 3 doses of fast-acting insulin or ultra fast analogue

LSC + Intensive controla

Multiple dose: 34 insulin dosesInsulin pump

LSC + Combination therapy:MET + SUMET + TZDMET + DPP-4 INHTZD + SUTZD + DPP-4 INHMET + INCRETIN ANALOGUE

Fasting glucose 126 mg/dL (7 mmol/L) to < 240 mg/dL (13.3 mmol/L) and/or HBA1c < 9%Fasting glucose 240 mg/dL (13.3 mmol/L) and/or HBA1c 9%

a Handled or advised by a specialist.

in Table 4. The pharmacological charac-teristics of insulin preparation and in-sulin analogues are included in Table 5.

2. How should a clinically-stable patientwith type 2 diabetes with mean fastingglycemia < 240 mg/dL (13.3 mmol/L),and HbA1c < 9 % be managed?Most individuals with type 2 diabetes

show few clinical signs or symptoms atonset. This is why many patients are di-agnosed late. If the patient is clinically sta-ble, has few symptoms, no ketosis, fastingblood glucose between 126 mg/dL (7mmol/L) and 240 mg/dL (13.3 mmol/L)and/or HbA1c < 9%, the cornerstone oftreatment is the initiation of a healthylifestyle with adequate nutrition, regularexercise, and cessation of smoking, if ap-plicable. Alcohol consumption should belimited to 1 drink/day for adult womenand 2 drinks/day for adult men.

In addition, Metformin (500 mg 3 /day) should be started in all patients,and can be gradually increased to 2.5 g/day, as needed, to achieve the treatmentgoal in a 3-month period. Besides itstherapeutic effects, Metformin has beenshown to decrease cardiovascular com-plications in retrospective (22, 23) andprospective analyses (8, 9) and has theadvantage of being easily accessible forvirtually all populations. Metformindose should be reduced in patients withan estimated glomerular filtration rate(eGFR) < 60 mL/min. The drug is con-traindicated if the eGFR is < 30 mL/min.The eGFR can be estimated by using theCockcroft-Gault formula (24) or theMRDS equation used in the Diet in RenalDisease Studyrecommended by theNational Kidney Disease Education Pro-gram (United States, 25). Likewise, Met-formin is contraindicated in patientswith alcoholism, severe chronic obstruc-tive pulmonary disease (COPD), and/ordecompensated heart, respiratory, orliver failure (26).

If Metformin is contraindicated, or incase of gastrointestinal intolerance, thefollowing options may be considered formonotherapy (27):

(a) Sulfonylureas: These are among themost effective oral drugs, with ro-bust clinical experience and low cost.However, the risk of hypoglycemia(especially with first generation, long-acting sulfonylureas) and weight gainshould be considered (28). The effi-cacy of sulfonylureas over the long-

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TABLE 3. Lifestyle recommendations to prevent and treat type 2 diabetes mellitus in LatinAmerica, 2010

A. Education is the most important factor in the treatment of diabetes mellitus. Patients and their familiesshould receive well-defined information to educate and empower them to make the right choicesconcerning lifestyle.

B. Aerobic physical activities should be performed for at least 30 minutes, 5 days/week, according to eachpatients characteristics. Anaerobic activities could be considered as complementary.

C. Nutritional medical therapy should be customized according to the baseline body mass index and physicalactivity level of each patient. Macronutrient content of the diet should be adjusted to 50%60%carbohydrates; 20%30% fat with less than 7% saturated fat; and 10%20% protein (minimum 1 g/kg ofideal weight per day)

D. Natural fiber intake should be 2030 g/day. E. Daily salt intake should be < 5 g in patients with diabetes and < 3 g in patients with associated

hypertension.F. Diet should consider availability and patient preference, while minimizing the use of processed foods. G. Alcohol consumption should be discouraged. H. Tobacco should not be allowed.

TABLE 4. Medications currently approved to treat type 2 diabetes, 2010

Mean daily Maximum dailyClass Drugs doses doses

Biguanide Metformin 850 mga 2 550 mgSulfonylureas Chlorpropamide 250 mgb 500 mg

Glibenclamide 5 mga 20 mgGlipizide 5 mga 20 mgGlimepiride 4 mgb 8 mgGliclazide 80 mga 320 mgGliclazide MR 60 mgb 120 mg

Meglitinides Nateglinide 60 mgc 360 mgRepaglinide 2 mgc 12 mg

Thiazolidinediones Rosiglitazone 4 mga 8 mgPioglitazone 30 mgb 45 mg

-glucosidase inhibitors Acarbose 50 mgc 300 mgMiglitol 25 mgc 100 mg

DPP-4 inhibitors/gliptines Sitagliptin 100 mgb 100 mgVildagliptin 50 mga 100 mgSaxaglipnin 5 mgb 5 mg

Incretine analoguesExenatide 20 mcgra 20 mcgrLiraglutide 1.2 mgb 1.8mg

aTwice a day.bOnce a day.c Three times a day.

TABLE 5. Characteristics of insulin preparations used in Latin America, 2010

Insulin Start of action Peak Duration

Regular human insulin 3060 min 23 hr 68 hrAspart 1020 min 12 hr 35 hrLispro 515 min 0.51.5 hr 46 hrGlulisine 510 min 12 hr 34 hrNPH insulin 24 hr 410 hr 1218 hrGlargine 24 hr No ~ 24 hrDetemir 0.82 hr No ~ 24 hrBiphasic human 70/30 0.51 hr 24 and 612 hr 1622 hrBiphasic aspart 70/30 515 min 12 and 612 hr 1622 hrBiphasic lispro 75/25 515 min 12 and 212 hr 1622 hrBiphasic lispro 50/50 515 min 12 and 612 hr 1622 hr

term is less than that of Metforminand glitazones.

(b) Meglitinides: These drugs are partic-ularly useful when post-prandialhyperglycemia is the main abnor-mality. Due to their short half-life,meglitinides can be used in patientswith renal failure (29).

(c) Glitazones: Insulin resistance and in-flammatory markers are decreasedwith glitazone therapy. Patientsshould be carefully selected for thistherapeutic option in order to reducethe risk of heart failure, coronaryevents, or fractures (particularly inpostmenopausal women) (30).

(d) Acarbose: Its main effect is on post-prandial glycemia. Acarbose reducesA1c values by 0.5%. Gradual titrationhelps improve gastrointestinal toler-ance (31).

(e) DPP-IV inhibitors or gliptins: Theserecently launched drugs prevent theinactivation of Glucagon-like peptide1 (GLP-1) by inhibiting the enzymedipeptidyl peptidase-4 (DPP-IV).Therefore, gliptins enhance and pro-long the action of the endogenouslyreleased GLP-1. DPP-IV inhibitorsreduces A1c values by 0.50.9%. Glip-tins are orally active, safe, and highlytolerable, with a minimal risk forhypoglycemic events. They are bodyweight neutral. These drugs havebeen used in combination with Met-formin, sulfonylureas, and thiazo-lidinediones. However, additionalevidence is required to assess thelong-term effects of the DPP-IV in-hibitors, in particular issues such assafety and their effectiveness in theprevention of the diabetes-relatedchronic complications (32).

(f) GLP-1 analogues: These drugs (exe-natide and liraglutide) were intro-duced to the Latin American marketsduring 2009. GLP-1 increases insulinoutput and decreases glucagon se-cretion in a glucose-dependent man-ner. Therefore, the risk of hypo-glycemia is minimal. One yearresults show that their use improvesA1c levels (0.79 to 1.12%) and bothfasting and post-prandial hyper-glycemia; in addition, a moderateweight loss effect occurs. GLP-1 ana-logues promote weight loss throughthe gastrointestinal side-effects andalso by slowing gastrointestinalmotility and inducing satiety. How-ever, the need for daily subcuta-

neous administration and their sideeffects (i.e., nausea and gastrointesti-nal symptoms) may limit their use.Additional evidence is required toassess the long-term effects of theGLP-1 analogues in the prevention ofdiabetes-related chronic complica-tions and long term safety (33, 34).

Public and private institutions shoulddecide which of these drugs should beused as the first option. The decisionshould be based on cost-effectivenessanalysis and individualized patient care.

3. What should be done if mono-therapy fails? The patient should reach treatment

goals (HbA1c < 7%) within 3 months ofmonotherapy. If this is not so, combina-tion therapy should be initiated. Combi-nations shown to be useful are listed inTable 6. The most widely-used combina-tion in Latin America is Metformin plusSulfonylurea. This combination providesgood therapeutic efficacy. Other optionsbased on Metformin may also be consid-ered at this stage: Metformin + Megli-tinides, Metformin + Glitazones, Met-formin + DPP-4 inhibitors, andMetformin + Incretin Analogues (6, 28,35, 36). Less popular combinations (e.g.,Sulfonylureas with Glitazones, Glita-zones with DPP-4 inhibitors, Acarbosewith Sulfonylureas, Metformin + Acar-bose, and Sulfonylureas with DPP-4 in-hibitors may be useful in certain situa-tions due to their synergistic mechanismof action; however, the evidence thatsupports their use is not as strong as thatfor conventional combinations.

Combination therapy with three drugsis indicated in some patients (37). Op-tions include the use of DPP-IV in-hibitors, GLP-1 analogue, or glitazones,in addition to Metformin and a sulfony-

lurea. The intervention of a diabetes spe-cialist could be considered in patientswho are not reaching the treatment tar-gets despite the use of three agents.

4. What should be done to manageoverweight patients not controlledby monotherapy and who continueto gain weight? Lack of adherence to a healthy lifestyle

is a contributing factor to not achievingtreatment goals in the clinically-stableobese patient with a HbA1c < 9% (38).These patients require closer monitoringand the support of a multidisciplinaryteam, if available, for the implementationof an adequate dietary plan, an exerciseprogram, and psychological support. Inaddition, Metformin dosage should betitrated to reach its maximal effect. Theuse of combination therapy that may pro-voke weight gain should be limited tocases that remain hyperglycemic despitelifestyle modifications. The timeframe forconsidering combination therapy will de-pend on the patients circumstances (39).

5. What should be done when treat-ment goals are not achieved with anoral combination? Failure to achieve treatment goals on

combination therapy, despite usingdrugs with differing mechanisms of ac-tion, indicates a significant deficit in in-sulin production. This is due to the pro-gressive decline in insulin secretorycapacity that occurs in type 2 diabetes. Tomeet HbA1c goals, insulin therapy will benecessary in such patients. Initially, con-trol can be achieved with a bedtime doseof Neutral Protamine Hagedorn (NPH)insulin or a long-acting insulin analogue(Glargine or Detemir) in combinationwith oral agents. Glargine can be given atany moment of the day.

Under this treatment scheme, insulindosage should be regularly titrated basedon fasting glycemia. Changes in dosageshould not be greater than 10% of thetotal dose. The frequency of the adjust-ments depends on the patient characteris-tics and the experience of the practitioner.Changes in the dosage on a daily basismay be necessary in severely hyper-glycemic patients. When the treatmentgoals are close to being achieved, it isbetter to adjust the amount of insulinevery 34 days. Frequent and largechanges in dosage may cause recurrenthypoglycemia and weight gain. A timeperiod of at least 13 months is recom-

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TABLE 6. Successful combination of oral anti-hyperglycemic agents with their evidence-based recommendation for patients with type2 diabetes, 2010

Combination Recommendation

Metformin + Sulfonylurea AMetformin + Glitazone AMetformin + Acarbose BMetformin + Meglitinide BSulfonylurea + Glitazone BSulfonylurea + Acarbose BGliptines + Metformin BMeglitinida + Glitazona B

Source: ALAD Guidelines (6).

mended to assess whether treatmentgoals are achieved before considering achange in treatment regime. With time,progression to full insulinization will benecessary. Of note, the combination of in-sulin with glitazones is not recom-mended due to the increased risk ofedema and heart failure.

Other management alternatives areavailable for intensifying insulin ther-apy. The choice depends on insulinavailability, patient requirements, meta-bolic behavior, and risk of hypogly-cemia. One option is a mixture of 2 typesof insulin, such as regular insulin andNPH insulin, or a combination of a shortacting insulin analogue (Lispro, Aspart,or Glulisine) with NPH insulin. The mix-tures may be prepared by the patient orfixed-dose preparations can be used.Premixes can be selected at a ratio of30:70, 25:75, or other less common pro-portions. Another option is 12 doses ofa long-acting analogue (Glargine or De-temir) with a dose of regular human in-sulin or a rapid-acting insulin analoguebefore each meal. Time of action, peakactivity, and duration of different in-sulins and insulin analogues are shownin Table 5 (40, 41). At this stage of inten-sive insulin therapy, referral of the pa-tient to a specialist is recommended.

6. How should a clinically unstable pa-tient with type 2 diabetes be managed?For patients with few clinical symp-

toms, no weight loss or ketosis, the pre-scription of oral combination therapy isrecommended. This can rapidly correct themetabolic state, reduce glucotoxicity, andcorrect fasting/post-prandial glycemiaand HbA1c. If there is a lack of responseafter a 13 month period, patients shouldbe started on an insulin regimen (42).

Symptomatic patients who are losingweight rapidly or are ketotic should re-ceive insulin therapy immediately. Anyof the insulin regimens described above is useful for the prompt correction of hy-perglycemia and nutritional status (43).Later, once these patients are stable andhave regained weight, the treatmentshould be reassessed; the possibility ofswitching to oral drugs can be consid-ered. This situation can occur especiallyin recent-onset diabetes. Other patientsmay need to be maintained on an insulinregimen. Some cases may be eligible for a more intensive therapeutic regimenwith multiple insulin doses or an insulinpump. Such patients should always be

treated by a specialist. It is assumed thatmeasures for adopting a healthy lifestyleare in place and reinforced regularly.

7. When should changes be made tothe therapeutic regimen? The adoption of a healthy lifestyle is

obligatory for the success of all treatmentmodalities. All therapeutic alternativesshould be given a reasonable amount oftime to evaluate their maximal efficacy.This is especially relevant if there is clin-ical improvement, weight stabilization,and gradual improvement of fasting andpost-prandial glucose and HbA1c values.A 13 month period is enough to reachexpected benefits. The dosage should al-ways be titrated based on monitoring offasting/post-prandial glycemia. Primarycare physicians are discouraged from de-laying the addition of an oral glucose-lowering agent or insulin. Clinical inertiais a contributing factor for not achievingtreatment targets in all health systems.

8. How should patients be monitored? Health care systems in Latin America

do not have comprehensive multidisci-plinary teams for the treatment of pa-tients with diabetes. In most countries,the primary care physician is responsi-ble for the treatment of a large propor-tion of the diabetic population. Physi-cians should instruct patients on how toself-monitor and manage their ownhealth. Self-monitoring is a fundamentaltool for all patients with diabetes; in par-ticular, those on insulin treatment whorequire intensive glucose monitoring. Aself-monitoring plan is a recommendedcomponent of patient management. Ithelps determine whether patients are onthe right track for achieving treatmentobjectives (44). Capillary glucose mea-surement has become more accessible inLatin America; however, the high cost ofglucometers and test strips is still a sig-nificant problem for many patients.

HbA1c determination is recommendedevery 34 months. It must be taken into account, however, that this index isnot readily available throughout LatinAmerica, and where it is available, cost isoften a deterrent.

9. When should a diabetes specialist beconsulted? The number of health professionals

specifically trained to manage patientswith diabetes is very limited in LatinAmerica. General practitioners are often

responsible for making treatment deci-sions during the early stages of the dis-ease. They do this with limited resourcesand time constraints. However, it is es-sential that practitioners aim to achievethe standards of diabetes care in theirpatients. Continuing medical educationfor primary care physicians must be apriority for national and internationalmedical institutes. Patients who do notachieve treatment goals within a 612month period should be referred to aspecialist. Likewise, those requiring in-tensive insulin regimens should be man-aged by a diabetologist/endocrinologist.

DISCUSSION

The health care systems of LatinAmerican countries must be restruc-tured to face the challenge that diabetesrepresents. Training of medical studentsand primary care physicians should beupdated to provide the necessary skillsfor successfully implementing diabetescare and promoting long-term adher-ence to therapy (45). In addition, dia-betes education programs are needed forboth patients and the general public.These actions will create awarenessabout the disease and its consequences.This step is crucial to achieving sus-tained changes in lifestyle and adherenceto therapy. If these actions are not imple-mented, a large percentage of the dia-betic population will remain outside ofthe treatment target levels (45, 46).

The health care associations and insti-tutes of Latin America should all be in-volved in creating a diabetes care actionplan. They can prepare position docu-ments that guide doctors in achievingbetter therapeutic results. They can alsoparticipate in the continuing educationof health professionals (47, 48). Localguidelines are necessary.

Adopting recommendations preparedfor other areas of the world may not befeasible due to economic, logistic, and/orcultural differences. Latin Americancountries share many ethnic, social, cul-tural, and lifestyle characteristics. Assuch, ALAD has produced specific rec-ommendations for Latin America for thelast 40 years. In 2006, ALAD publishedguidelines for the diagnosis, control, andtreatment of the patient with type 2 dia-betes, i.e., the Guas ALAD de Diagns-tico, Control y Tratamiento de la DiabetesMellitus tipo 2 (6). This document wasapproved and recommended by the Pan

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American Health Organization (PAHO)as guidelines for Latin America (49).

Since 2006, new strategies, medica-tions, and information have arisen forvarious aspects of type 2 diabetes treat-ment. For this reason, ALAD called uponthe national diabetes and/or endocrinol-ogy associations to produce a consensusdocument. The aim was to integrate theALAD guidelines with important infor-mation from each organization to pro-duce a common standard for diabetes inLatin America. The recommendationsare applicable to practically every pa-tient, with some possible exceptions. Insummary, the document:

1. Acknowledges the importance ofreaching treatment targets early, es-pecially in the initial years of thedisease. The document recommendsan HbA1c level below 7% as thetarget for glucose control. If the clin-ical condition of the patient allows,an HbA1c goal of 6.5% should beconsidered.

2. Defines two clinical profiles that dif-fer by HbA1c levels, body weight, andthe presence/absence of ketosis.

3. Includes special notes regarding obesepatients who are unable to reach glu-cose treatment goals and continue togain weight. This phenotype is oftenoverlooked by other guidelines.

4. Recommends the early use of combi-nation therapy and the timely addi-tion of insulin in patients who do notachieve adequate glucose control.Also included are combinations withsufficient clinical evidence to supporttheir use. Primary care physicians arediscouraged from delaying the addi-tion of an oral glucose lowering agentor insulin because this practice resultsin prolonged exposure to the adverseeffects of hyperglycemia.

5. Describes clinical traits of the avail-able glucose-lowering agents to aid in

selecting from among the treatmentoptions.

6. Recognizes that, in Latin America,logistics can limit the use HbA1c deter-minationthe gold standard for gly-cemic controland offers regular de-termination of venous and capillaryglycemia as an acceptable alternative.The position statement recommendstreatment targets for both HbA1c andfasting glucose levels. In addition, theimportance of individual practitionersas providers of diabetes care in LatinAmerica is highlighted. However, the need to create multidisciplinarygroups is also reinforced.

7. Provides clinical indications and pos-sible contraindications for all of theexisting glucose lowering agents.None are excluded. It is the responsi-bility of each medical institute andALAD to educate physicians to en-sure correct medication usage.

8. Was prepared and approved by dia-betes specialists/physicians, leaders,and experts in Latin America.

Although the evidence supporting cur-rent clinical recommendations is univer-sal, the quality of diabetes care depends ongeographic factors. Because this consensustakes into account the unique challengesfaced by patients and physicians in LatinAmerica, its strategies are more feasibleand it is hoped that its impact will go far-ther than that of past efforts to improve di-abetes management. Primary care phy-sicians are the principal focus of thisreview. Special emphasis is given to themanagement of the obese patient withtype 2 diabetes not reaching the treatmenttargets. With the help of all participatinginstitutions, we expect that this consensusdocument will be helpful to improving thequality of diabetes care in Latin America.

Acknowledgments. The authors wishto recognize the ALAD consensus group:

Coordinators: Juan Rosas Guzman (Presi-dent, ALAD), Ruy Lyra (Vice-President,Pan American Endocrinology Federation)

Participant associations (represented by):Asociacin Latinoamericana de Diabetes(Juan Rosas Guzmn); Sociedad Mexicanade Nutricin y Endocrinologa (Carlos A.Aguilar-Salinas and Eduardo Garca Gar-ca); Sociedad Brasileira de Endocrinolo-gia e Metabologia (Ruy Lyra, MarcosTambascia); Asociacin Salvadorea deEndocrinologa Diabetes y Nutricin (Car-los Alvayero); Asociacin Guatemaltecade Endocrinologa Metabolismo y Nutri-cin (Vinicio Granados); Sociedad Ecuato-riana de Endocrinologa y Metabolismo(Rodrigo Rovayo Prcel); Sociedad deDiabetologa y Nutricin del Uruguay(Silvia Garca); Sociedad Argentina deDiabetes (Gustavo Frechtel); Sociedad Bo-liviana de Endocrinologa, Metabolismo yNutricin (Elizabeth Duarte); AsociacinPanamea de Endocrinologa, Diabetes yMetabolismo (Rolando Caballero); Fede-racin Mexicana de Diabetes (GuillermoRodrguez); Sociedad Hondurea de En-docrinologa (Mario Valdz Lanez); So-ciedad Chilena de Endocrinologa y Dia-betes (Carmen Gloria Aylwin); SociedadBrasileira de Diabetes (Marilia BritoGomes, Saulo Cavalcanti, and AntonioCarlos Lerario); Sociedad Dominicana deEndocrinologa (Flix Escao Polanco);Asociacin Nicaraguence de Endocri-nologa, Diabetes y Obesidad (EnriqueMedina Sandino); Federacin Venezolanade Unidades de Diabetes (Matilde Garcade Blanco); Sociedad Cubana de Endo-crinologa (Daysi Navarro); FederacinDiabetolgica Colombiana (Gustavo Mr-quez Salom); Sociedad Peruana de Endo-crinologa (Isaac Crespo Retes); and So-ciedad Cubana de Diabetes (Oscar DazDaz).

The authors express their gratitute toRoopa Mehta for editorial assistance.

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Special report Guzmn et al. Latin American consensus statement for type 2 diabetes treatment

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Guzmn et al. Latin American consensus statement for type 2 diabetes treatment Special report

Amrica Latina se enfrenta a algunos retos excepcionales en el tratamiento de la dia-betes mellitus tipo 2. La Asociacin Latinoamericana de Diabetes (ALAD) reuni a lasasociaciones mdicas de 17 pases latinoamericanos con el fin de producir una decla-racin de consenso sobre el tratamiento de la diabetes tipo 2. El objetivo de ese docu-mento es brindar recomendaciones prcticas que guen a los mdicos a lo largo de unsencillo proceso decisorio para el tratamiento de los pacientes. Los elementos funda-mentales para la toma de decisiones teraputicas son la gravedad de la hiperglucemia,el estado clnico del paciente (estable o con descompensacin metablica) y el ndicede masa corporal. El documento contiene un apartado dedicado especficamente a lospacientes obesos y la informacin se presenta en forma de preguntas clnicas suma-mente pertinentes. El algoritmo se basa en las recomendaciones cientficas de lasdirectrices de la ALAD del ao 2006 (documento preparado con un mtodo basado en datos probatorios) y en datos obtenidos de estudios controlados aleatorizadosrecientes.

Diabetes mellitus tipo 2; obesidad; consenso; guas de prctica clnica como asunto;Amrica Latina.

RESUMEN

Tratamiento de la diabetestipo 2 en Amrica Latina:

declaracin de consenso delas asociaciones mdicas de

17 pases latinoamericanos

Palabras clave