Los cielos y la Tierra pasarán, pero mi palabra, no pasará

Presentación del tema: "Los cielos y la Tierra pasarán, pero mi palabra, no pasará"— Transcripción de la presentación:

1 Los cielos y la Tierra pasarán, pero mi palabra, no pasará
Diabetes Gestacional actualidades 2013 Mateo 24:35

2 Diagnóstico y Tratamiento actual
Randomized treatment trials and choice of threshold values. Two randomized controlled trials comparing active treatment versus standard obstetric care for mild GDM have been conducted during the years in which the HAPO study was carried out (47,48). In both randomized controlled trials, treatment, achieved primarily by diet/lifestyle modification, resulted in reduced birth weight and frequency of LGA births and preeclampsia. Recruitment processes and glycemic values of participants were not identical in the randomized controlled trials and the HAPO observational study. However, there was substantial overlap between glucose values used for inclusion in the randomized controlled trials and those recommended in this report as new threshold values. Furthermore, frequencies of outcomes such as LGA or birth weight >90th percentile and preeclampsia in usual care versus treatment arms of the randomized controlled trials are similar to those observed in the HAPO study among women with one or more glucose values that meet or exceed the threshold, compared with those with all values below threshold (supplemental Table B). Although not directly comparable, it was concluded that results of the two randomized controlled trials (47,48) and HAPO (25,26) are highly complementary Dra. Julia Vázquez Lara Endocrinologo UMAE 23 IMSS- Monterrey

3 El embarazo es diabetogénico

4 Diabetes Gestacional datos históricos
Solo CTG Desde 1964: norte de USA Han cambiado los valores para establecer el dx. 2 criterios: ADA y OMS hasta 2008

5 Diabetes Gestacional diagnóstico A.D.A.
C.T.G. Basal: 95mg 1 h: mg 2h: mg 3h: mg Diabetes Care 2000 TAMIZAJE Carga de 50g Glucosa 1hora > 130mg/dl.

6 criterios para dx Diabetes Gestacional 2008
O.M.S. A.D.A. A.L.A.D.

7 Diabetes Gestacional diagnóstico
ALAD CTG de la OMS >140mg/dl. a las 2 hs. Hiperglucemia: 2 valores 100 o mayor Revista ALAD dic 2008

8 Más fácil es que pasen el cielo y la tierra, que se frustre una tilde de la ley

9 IADPSG Carencia de uniformidad Internacional en el Dx
Grados menores de hiperglucemia se asocian a riesgo elevado de resultados perinatales Some suggest that criteria currently in wide use for the diagnosis of GDM are too restrictive and that lesser degrees of hyperglycemia increase risk of adverse perinatal outcomes (11–16). Conversely, others believe that systematic efforts to identify GDM should be stopped unless data become available to link significant morbidities to specific degrees of glucose intolerance (8). Lack of international uniformity in the approach to ascertainment and diagnosis of GDM has been a major hurdle (2). Questions have been raised regarding cost-effectiveness and benefit of detecting and treating GDM. Recent recommendations of the U.S. Preventive Services Task Force, the U.K. National Health Service, and the Canadian Task Force on the Periodic Health Examination assert that there is not sufficient high-level evidence to make a recommendation for, or against, screening for GDM (17–19). Recently, a cost-effectiveness study undertaken by the U.K. National Institute for Health and Clinical Excellence concluded that “screening, diagnosis, and treatment of gestational diabetes is cost-effective” (20). As currently defined (1,2), GDM includes a subgroup with more severe hyperglycemia (similar to that seen in preexisting diabetes) that presents special issues concerning management during pregnancy and postpartum follow-up. The issues raised by inclusion of this subgroup with those with GDM are of greater concern because of the rising prevalence of obesity, type 2 diabetes, and other metabolic disturbances among younger age-groups (21–23). The HAPO study was designed to clarify risks of adverse outcome associated with degrees of maternal glucose intolerance less severe than those with overt diabetes during pregnancy (24). HAPO study results (25,26) were considered in depth in arriving at the recommendations for diagnosis of GDM presented in this report. Recommendations for detection of overt diabetes during pregnancy are based on the opinions of the IADPSG Consensus Panel members because information from prospective studies or appropriately designed clinical trials is not available.

10 The International Association of Diabetes and Pregnancy Study Groups ( IADPSG )
Se formó en 1998 225 expertos Para incrementar la calidad de atención, investigación, y educación con abordaje internacional. The International Association of Diabetes and Pregnancy Study Groups (IADPSG) was formed in 1998 as an umbrella organization to facilitate collaboration between the various regional and national groups that have a primary or significant focus on diabetes and pregnancy. The principal objectives of IADPSG are to foster an international approach to enhancing the quality of care, facilitating research, and advancing education in the field of diabetes in pregnancy. During 11–12 June 2008, the IADPSG sponsored an International Workshop- Conference on Gestational Diabetes Diagnosis and Classification in Pasadena, California. More than 225 conferees from 40 countries reviewed published results of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, additional unpublished HAPO study findings, and results of other work that examined associations of maternal glycemia with perinatal and long-term outcomes in offspring. Conferees then held regional caucuses to consider clinical implications of the information that had been presented. On 13 June 2008, the IADPSG Consensus Panel (with representation from the 10 member organizations of the IADPSG and other organizations with an interest in diabetes and pregnancy) was convened. Members of the IADPSG Consensus Panel are listed in the online-only appendix, available at  Subsequently, the IADPSG Consensus Panel reviewed further HAPO study results. Through this process, the consensus summarized in this report was reached.

11 IADPSG Diseñaron un estudio que asoció los niveles de glucosa en embarazadas con resultados adversos El estudio HAPO Los resultados se han usado para establecer nuevos criterios dx de DMG The objective of the HAPO study was to clarify associations of levels of maternal glucose lower than those diagnostic of diabetes with perinatal outcome (24,25). This was accomplished by performing a 75-g oral glucose tolerance test (OGTT) on a heterogeneous, multinational, multicultural, ethnically diverse cohort of ∼25,000 women in the third trimester of gestation. Medical caregivers were blinded to status of glucose tolerance except when predefined criteria were met (fasting plasma glucose [FPG] >5.8 mmol/l [105 mg/dl] and/or 2-h plasma glucose >11.1 mmol/l [200 mg/dl]) (24). It was anticipated that this would provide data on associations between maternal glycemia and risk of specific adverse outcomes that could be used to derive internationally acceptable criteria for diagnosis and classification of GDM. Primary outcomes in the blinded HAPO cohort were birth weight >90th percentile, primary cesarean section delivery, clinically defined neonatal hypoglycemia, and cord C-peptide >90th percentile. Secondary outcomes were preclampsia, preterm delivery, shoulder dystocia/birth injury, hyperbilirubinemia, and intensive neonatal care. Importantly, there were continuous graded relationships between higher maternal glucose and increasing frequency of the primary outcomes, independent of other risk factors (25). Similar associations were also observed for secondary outcomes (25,26). Associations did not differ among centers; thus, the results are applicable to all centers and can be used globally to develop outcome-based criteria for classifying glucose metabolism in pregnancy. Because associations were continuous with no obvious thresholds at which risks increased, it was concluded that a consensus was required to translate these results into clinical practice. HAPO data show strong linear associations of risks for >90th percentiles of birth weight, cord C-peptide, and percent body fat with each of three measures of maternal glucose (FPG, 1-h, and 2-h post–75-g load). In determining the recommendations for diagnostic thresholds, associations with these outcomes were used to select glucose concentrations as potential diagnostic threshold values (supplemental Fig. 1). Published data support this decision. Fetal macrosomia (LGA) is a major indicator of the effects of hyperglycemia during pregnancy (12,35,36). Associations of LGA and excess adiposity with fetal hyperinsulinemia are strong and independent of confounders (26,37,38). This is supported by experiments in pregnant monkeys (39). Risks of difficult delivery and maternal/neonatal damage associated with fetal macrosomia (9,40) were confirmed in large populations (41,42). Long-term risks associated with fetal macrosomia in infants of women with GDM (independent of confounders) include childhood overweight (43,44) and metabolic factors that may increase risk of cardiovascular disease (CVD) (45). In the HAPO study, frequencies of study outcomes were compared across the entire distribution of glucose concentrations, with the lowest glucose concentration ranges used as the reference for calculation of odds ratios (ORs) (25). However, the IADPSG Consensus Panel decided that for selection of diagnostic thresholds, mean values for FPG, 1-h, and 2-h OGTT plasma glucose concentrations (4.5, 7.4, and 6.2 mmol/l, respectively) for the entire study cohort should be used as reference. Concentrations at which ORs for specific outcomes in adjusted models reached predefined values, with glucose modeled as a continuous variable, were then determined. After review of these data, the IADPSG Consensus Panel concluded that the predefined value for the OR at the threshold relative to the mean should be 1.75 (ORs 1.5 and 2.0 were also considered, see OTHER CONSIDERATIONS below). Finally, proportions of participants who would be identified by measurement of FPG only, FPG plus 1-h glucose concentration, and FPG plus both 1-h and 2-h plasma glucose concentrations were considered

12 Estudio HAPO 2006 -2007 25mil pacientes 9 paises, todas las razas
CTG de OMS Resultados perinatales NEJM Mayo 2008 OBJECTIVE To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. RESEARCH DESIGN AND METHODS Eligible pregnant women underwent a 75-g OGTT at 24–32 weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. RESULTS Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. CONCLUSIONS On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women. Received August 31, 2011. Accepted December 4, 2011.

13 Resultados de HAPO The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was performed in response to the need for internationally agreed upon diagnostic criteria for gestational diabetes, based upon their predictive value for adverse pregnancy outcome. Increases in each of the 3 values on the 75-g, 2-hour oral glucose tolerance test are associated with graded increases in the likelihood of pregnancy outcomes such as large for gestational age, cesarean section, fetal insulin levels, and neonatal fat content. Based upon an iterative process of decision making, a task force of the International Association of Diabetes and Pregnancy Study Groups recommends that the diagnosis of gestational diabetes be made when any of the following 3 75-g, 2-hour oral glucose tolerance test thresholds are met or exceeded: fasting 92 mg/dL, 1-hour 180 mg/dL, or 2 hours 153 mg/dL. Various authoritative bodies around the world are expected to deliberate the adoption of these criteria

14 CTG de 75 g Criterios actuales Glucosa ayuno > 92mg/dl
Glucosa 1 hora > 180mg/dl Glucosa a 2 horas >153mg/dl Dx. Uno o Varios son anormales Diagnostic recommendations The stepwise consideration of the HAPO study data described above led to the recommendation of the values for FPG, 1-h, and 2-h plasma glucose concentration (Si and conventional) indicated in Table 1 as diagnostic thresholds. These thresholds are the average glucose values at which odds for birth weight >90th percentile, cord C-peptide >90th percentile, and percent body fat >90th percentile reached 1.75 times the estimated odds of these outcomes at mean glucose values, based on fully adjusted logistic regression models. At least one of these thresholds must be equaled or exceeded to make a diagnosis of GDM. Measuring FPG alone identified 8.3% of the cohort as having GDM. Adding measurement of the 1-h plasma glucose identified an additional 5.7%; adding the 2-h plasma glucose measurement identified another 2.1% of the cohort. Among the HAPO cohort, 11.1% had only one elevated result, 3.9% had two elevated results, and 1.1% had elevation of all three results. In addition, 1.7% of the cohort was unblinded due to an FPG or 2-h plasma glucose value on the enrollment OGTT above predefined values of 5.8 mmol/l (105 mg/dl) or 11.1 mmol/l (200 mg/dl), respectively (25). Thus, by these new criteria, the total incidence of GDM was 17.8%; the FPG plus 1-h plasma glucose levels identified a large majority of these individuals Adjusted ORs and 95% CIs for associations between maternal glucose and HAPO study outcomes are in supplemental Table A. ORs are for the difference in glucose between the mean glucose value and the recommended threshold. In addition to the outcomes used to determine the thresholds, there were strong associations between maternal glucose and preeclampsia (ORs 1.40–1.57) and shoulder dystocia and/or birth injury (1.30–1.43). The frequencies of HAPO study outcomes when all three glucose measures were below threshold values and when any one or more values were greater than or equal to threshold concentration were compared (supplemental Table B). The frequency of birth weight, C-peptide, or percent infant body fat >90th percentile was approximately twofold greater when any of the glucose values were greater than or equal to the threshold. The frequency of preeclampsia was twofold higher when one or more glucose values met or exceeded threshold, and frequencies of preterm delivery and primary cesarean section were >45% higher. Other considerations Measurement of glucose. The frequencies and ORs for outcomes on which the recommended diagnostic thresholds are based increase substantially over relatively small changes in glucose concentration (supplemental Fig. 1 and Table A). Therefore, to achieve reliable diagnosis and classification of hyperglycemia in pregnancy, clinical laboratories must measure venous plasma or serum glucose using an enzymatic method with high accuracy and precision. This includes proper sample collection and processing to minimize pre-analytic glycolysis and proper laboratory analysis (34,46). Capillary and venous plasma glucose concentrations differ and are not interchangeable, and conversion factors do not accurately estimate equivalent values (46). Alternative OR/threshold combinations. Consideration was given to glucose values and outcome frequencies for adjusted ORs of 1.5 and 2.0. The threshold OR of 1.5 identified 25% of the cohort with one or more glucose values that met or exceeded the threshold. The proportion of the cohort with FPG equal to or greater than threshold at ORs of 1.5, 1.75, or 2.0 (5.0, 5.1, and 5.3 mmol/l or 90, 92, or 95 mg/dl, respectively) differed substantially, representing ∼12, 8, and 4%, respectively. At ORs of 2.0, frequencies of birth weight, cord serum C-peptide, or percent infant body fat >90th percentile in those meeting threshold were modestly higher than those for OR 1.75 (supplemental Table B), but the number of participants meeting threshold decreased from 16.1 to 8.8%, meaning that the higher thresholds would fail to identify many cases with nearly comparable risk of adverse outcomes. Rounding threshold values to easy-to-remember numbers. Values such as 5.0 and 9.0 mmol/l (90 and 155 mg/dl, respectively) for FPG and 2-h plasma glucose would be somewhat easier to remember than those indicated in Table 1. However, this strategy is not feasible. First, as indicated above, arbitrarily choosing an FPG threshold of 5.0 mmol/l (90 mg/dl) would substantially affect the proportion of women meeting a diagnostic threshold. Second, both Si and standard units are widely used, and the numbers are not equally easy or difficult to remember for both units of measure. The values in Table 1 represent the best choice from a clinical perspective, and they meet the predefined strength of association from an epidemiological perspective.

15 asociación entre glucosa materna y resultados adversos
Otros estudios asociación entre glucosa materna y resultados adversos sin criterios de DMG de Indios Pima Danés Canadiense USA: Sacks, Ferrara Data from numerous studies are consistent with HAPO study results. In Pima Indians, Pettitt et al. (27) found that maternal plasma glucose concentration during pregnancy (measured 2 h after a 75-g load) had a continuous association with adverse pregnancy outcomes (LGA and cesarean section). A Danish study of pregnant women with mild glucose intolerance but without GDM found a linear association between maternal 2-h glucose and cesarean delivery, spontaneous preterm delivery, shoulder dystocia, and macrosomia after adjustment for confounders (28). Another analysis of that cohort (11) showed a linear relationship between maternal fasting glucose and macrosomia. The Toronto Tri-Hospital Study showed continuous associations between maternal glycemia and adverse pregnancy outcomes (29). Sacks et al. (30) found associations between FPG and the 2-h value on a 75-g OGTT and macrosomia in a mixed ethnic U.S. cohort (61% Hispanic). In a multiethnic U.S. population, Ferrara et al. (16) found risk of severe macrosomia, neonatal hypoglycemia, and hyperbilirubinemia increased with increasing number of abnormal glucose values according to current American Diabetes Association cut points (2,5) among women who did not meet National Diabetes Data Group criteria for GDM (31). Some studies cited above and others were presented at the IADPSG Pasadena meeting. The results were consistent with HAPO findings indicating that associations between maternal glycemia and adverse outcomes are continuous across the range of glucose concentrations below levels diagnostic of diabetes (25,26). As a result of the extensive efforts used to standardize procedures for participant enrollment (24,25), laboratory analyses (34), data collection (24,25), and analysis of results (25,26), HAPO data were used as the basis for the new GDM diagnostic thresholds recommended in this report

16 Impacto a la descendencia
Glucosa materna está relacionada a tolerancia a la glucosa, sobrepeso, obesidad y diabetes en la descendencia a los 5 a 7 años There are studies relating maternal glycemia to long-term outcomes in offspring. Pima Indian data demonstrated a direct association between maternal glycemia (in women whose glucose concentrations were in the range found in the blinded HAPO cohort) and offspring's long-term relative weight and degree of glucose tolerance, and it was a risk factor for diabetes and/or impaired glucose tolerance during the female offspring's pregnancies (32). Hillier et al. (33) assessed offspring of mothers receiving care in a large, diverse health care practice. Adiposity in offspring at 5–7 years of age was significantly associated with measures of maternal glycemia (50-g glucose challenge and/or 100-g OGTT) during pregnancy. This suggests that we may expect similar outcomes in offspring from the HAPO study.

17 Más fácil es que pasen el cielo y la tierra, que se frustre una tilde de la ley

18 Suma de estrategias de detección . . . Criterios Actuales
DMG por CTG de OMS Diabetes 2 en el embarazo Diabetes Care mar 2010 Diabetes Care 2011 The overall strategy recommended by the IADPSG Consensus Panel for detection and diagnosis of hyperglycemic disorders in pregnancy is summarized in Table 2. Two discrete phases are included. The first is detection of women with overt diabetes not previously diagnosed or treated outside of pregnancy. Universal early testing in populations with a high prevalence of type 2 diabetes is recommended, especially if metabolic testing in this age-group is not commonly performed outside of pregnancy. Well-designed studies should be conducted to determine whether it is beneficial and cost-effective to perform an OGTT in women who do not have overt diabetes at early testing but have indeterminate nondiagnostic results. The second phase is a 75-g OGTT at 24–28 weeks' gestation in all women not previously found to have overt diabetes or GDM.

19 CTG de 75 g Criterios actuales Glucosa ayuno > 92mg/dl
Glucosa 1 hora > 180mg/dl Glucosa a 2 horas >153mg/dl Dx. Uno o Varios son anormales Diagnostic recommendations The stepwise consideration of the HAPO study data described above led to the recommendation of the values for FPG, 1-h, and 2-h plasma glucose concentration (Si and conventional) indicated in Table 1 as diagnostic thresholds. These thresholds are the average glucose values at which odds for birth weight >90th percentile, cord C-peptide >90th percentile, and percent body fat >90th percentile reached 1.75 times the estimated odds of these outcomes at mean glucose values, based on fully adjusted logistic regression models. At least one of these thresholds must be equaled or exceeded to make a diagnosis of GDM. Measuring FPG alone identified 8.3% of the cohort as having GDM. Adding measurement of the 1-h plasma glucose identified an additional 5.7%; adding the 2-h plasma glucose measurement identified another 2.1% of the cohort. Among the HAPO cohort, 11.1% had only one elevated result, 3.9% had two elevated results, and 1.1% had elevation of all three results. In addition, 1.7% of the cohort was unblinded due to an FPG or 2-h plasma glucose value on the enrollment OGTT above predefined values of 5.8 mmol/l (105 mg/dl) or 11.1 mmol/l (200 mg/dl), respectively (25). Thus, by these new criteria, the total incidence of GDM was 17.8%; the FPG plus 1-h plasma glucose levels identified a large majority of these individuals Adjusted ORs and 95% CIs for associations between maternal glucose and HAPO study outcomes are in supplemental Table A. ORs are for the difference in glucose between the mean glucose value and the recommended threshold. In addition to the outcomes used to determine the thresholds, there were strong associations between maternal glucose and preeclampsia (ORs 1.40–1.57) and shoulder dystocia and/or birth injury (1.30–1.43). The frequencies of HAPO study outcomes when all three glucose measures were below threshold values and when any one or more values were greater than or equal to threshold concentration were compared (supplemental Table B). The frequency of birth weight, C-peptide, or percent infant body fat >90th percentile was approximately twofold greater when any of the glucose values were greater than or equal to the threshold. The frequency of preeclampsia was twofold higher when one or more glucose values met or exceeded threshold, and frequencies of preterm delivery and primary cesarean section were >45% higher. Other considerations Measurement of glucose. The frequencies and ORs for outcomes on which the recommended diagnostic thresholds are based increase substantially over relatively small changes in glucose concentration (supplemental Fig. 1 and Table A). Therefore, to achieve reliable diagnosis and classification of hyperglycemia in pregnancy, clinical laboratories must measure venous plasma or serum glucose using an enzymatic method with high accuracy and precision. This includes proper sample collection and processing to minimize pre-analytic glycolysis and proper laboratory analysis (34,46). Capillary and venous plasma glucose concentrations differ and are not interchangeable, and conversion factors do not accurately estimate equivalent values (46). Alternative OR/threshold combinations. Consideration was given to glucose values and outcome frequencies for adjusted ORs of 1.5 and 2.0. The threshold OR of 1.5 identified 25% of the cohort with one or more glucose values that met or exceeded the threshold. The proportion of the cohort with FPG equal to or greater than threshold at ORs of 1.5, 1.75, or 2.0 (5.0, 5.1, and 5.3 mmol/l or 90, 92, or 95 mg/dl, respectively) differed substantially, representing ∼12, 8, and 4%, respectively. At ORs of 2.0, frequencies of birth weight, cord serum C-peptide, or percent infant body fat >90th percentile in those meeting threshold were modestly higher than those for OR 1.75 (supplemental Table B), but the number of participants meeting threshold decreased from 16.1 to 8.8%, meaning that the higher thresholds would fail to identify many cases with nearly comparable risk of adverse outcomes. Rounding threshold values to easy-to-remember numbers. Values such as 5.0 and 9.0 mmol/l (90 and 155 mg/dl, respectively) for FPG and 2-h plasma glucose would be somewhat easier to remember than those indicated in Table 1. However, this strategy is not feasible. First, as indicated above, arbitrarily choosing an FPG threshold of 5.0 mmol/l (90 mg/dl) would substantially affect the proportion of women meeting a diagnostic threshold. Second, both Si and standard units are widely used, and the numbers are not equally easy or difficult to remember for both units of measure. The values in Table 1 represent the best choice from a clinical perspective, and they meet the predefined strength of association from an epidemiological perspective.

20 Diabetes 2 dx en el embarazo
Pacientes no conocidas con DM 2 Se detectan en el primer trimestre con glucosas 126mg o mayor

21 Categorias de Factores de Riesgo
Riesgo Alto: hasta 15% Riesgo Bajo:1 a 4% Riesgo Intermedio:5 a7% Bajo Riesgo: 1 a 4% Riesgo Intermedio: 5 a 7% Riesgo Alto: hasta 15%

22 Prevalencia Diabetes Gestacional
Monterrey 80,s : 5.7% 98 : 9% 2007: 17%

23 Diabetes Gestacional Factores de riesgo
Raza latina Fam con Diabetes Obesidad, SOP Macrosómicos Abortos y Obitos Pre eclampsia o DMG previa

24 Diabetes y Embarazo resultados perinatales adversos
Macrosomía Fetopatía Diabética Prematurez Obito Incremento de hospitalización RN

25 Diabetes y Embarazo resultados perinatales adversos
Preclampsia aumento de Cesáreas Infecciones y APP

26 Diabetes Gestacional representa
alteraciones de resistencia y / o deficiencia de Insulina PreDiabetes y Diabetes 2 materna en posparto

27 Efecto de Hiperglucemia Intrauterina
Hiperfunción pancreática fetal Mayor Obesidad Infantil y en Adolescencia DM 2 en edades muy tempranas

28 haciendo el diagnóstico de Diabetes Gestacional

29 Haciendo el Diagnóstico ¿Cómo?
Curva de Tolerancia a Glucosa Glucosa de ayuno: hiperglucemia

30 Diabetes Gestacional Diagnóstico

31 Haciendo el Diagnóstico ¿Cuándo?
1ª trimestre: en realidad son tipo 2 2ª trimestre: principalmente <20sem inicio temprano, con varios FR, se dx. con glucosa de ayuno 3ª trimestre: se dx. con CTG Todo el embarazo

32 Haciendo el Diagnóstico ¿a quién?
A toda mujer embarazada

33 Diabetes Gestacional pruebas Dx.
Varios Factores de Riesgo Glucosas de ayuno mensuales CTG: en cada trimestre

34 Conclusión . . . Pensar en DMG Hacer las pruebas dx Establecer el dx
Reducir morbilidad perinatal

35 Los cielos y la Tierra pasarán, pero mi palabra, no pasará
Mateo 24:35 Diabetes Gestacional Tratamiento Actual

36 Metas de Control Glucosa de ayuno: 60 a 95mg
Glucosa Posprandial 1h: <140mg Glucosa Posprandial 2h: <120mg Hemoglobina Glucosilada: < 6%

37 Monitoreo glucémico La frecuencia depende de la severidad de las glucosas Semanal, Quincenal o diario Pos prandial: si el dx. fue CTG o se requiere Insulina

38 Tratamiento tradicional
Dieta especial Ejercicio diario Insulina

39 Tx. Diabetes y Embarazo Seguir los principios de un paciente diabético
DIETA Seguir los principios de un paciente diabético Debe incluirse 1 o 2 colaciones Puede incluirse edulcurantes artificiales

40 Tx. Diabetes y embarazo EJERCICIO Debe ser diario 30 minutos
Caminata lenta

41 Tx. Diabetes y embarazo INSULINA Cuando no se consiguen las metas de control con dieta y ejercicio en 2 semanas

42 Insulina Humana Intermedia
Tx. Diabetes y embarazo Insulina Humana Intermedia Se requiere iniciar con dosis bajas, crecientes Se requieren 2 dosis en la mayoría, pues está insulina no cubre 24 hs. y p evitar hipoglucemias

43 Los cielos y la Tierra pasarán, pero mi palabra, no pasará
Mateo 24:35 Tratamiento con Metformin

44 Diabetes Gestacional etiología
Resistencia a la Insulina Obesidad y por el efecto antagónico de las hormonas del embarazo Se identifican por Hiperglucemia de ayuno

45 Tx. Metformin Porque es excelente fármaco para reducir la Resistencia a la Insulina No es teratogénico 70% de pacientes con DMG logran adecuado control

46 Tratamiento Diabetes y Embarazo
METFORMIN Reduce glucemia de ayuno y posprandial Regula el apetito y la ganancia de peso Menor macrosomía y menor peso en los productos

47 Tratamiento Diabetes y Embarazo
METFORMIN Hay publicaciones de uso en embarazo en los 70,s Un estudio grande que compararon Metformin con un grupo control y encontraron resultados perinatales similares NEJM . Mayo 2008 Otros estudios recientes

48 Estudio ECA australiano 2006 750 pacientes Metformin vs Insulina
Estudio MiG Estudio ECA australiano 2006 750 pacientes Metformin vs Insulina Los resultados perinatales fueron similares en ambos grupos NEJM mayo 2008 The MiG study has had ethics committee approval at all participating sites and informed written consent was obtained from all recruits. The study design is summarized in Fig. 1. Women 18–45 years old with GDM who are at 20–33 weeks’ gestation in a singleton pregnancy are eligible for study entry if home blood glucose monitoring includes a fasting glucose >5.4 mmol/l or 2-h postprandial glucose >6.7 mmol/l after diet and exercise advice has been given. More specific criteria are avoided, as clinicians base their decision about treatment on additional factors, such as gestation and fetal size. Women who have glucose elevations consistent with undiagnosed diabetes are eligible. Exclusion criteria include women who have a contraindication to taking metformin, a prepregnancy diagnosis of diabetes, a recognized fetal anomaly, or, at the time of study entry, ruptured membranes, gestational hypertension, preeclampsia, or fetal abdominal circumference <10th percentile. Women who consent are randomized to metformin or insulin treatment with stratification by site (as it is recognized there are variations in thresholds for treatment and glycemic aims between centers) and gestation (20–27 and 28–33 weeks). Treatment is initiated the following day, after checking results of a fasting blood sample that includes measurement of renal and liver function to ensure unexpected contraindications to metformin treatment are not missed. Metformin is started at a dose of 500 mg daily and increased up to 2,500 mg daily as tolerated and depending on maternal glucose levels. All sites have agreed to aim for fasting capillary glucose levels <5.5 mmol/l and 2-h postprandial levels <7.0 mmol/l, although a number of sites aim for lower levels. If inadequate diabetes control is achieved with metformin, insulin is started, but metformin is continued. Metformin is stopped if significant maternal conditions arise, such as severe preeclampsia, sepsis, or pregnancy cholestasis and also if fetal growth restriction develops. Insulin is prescribed as usual clinic practice, typically a short-acting insulin analog before meals and intermediate insulin once or twice daily. At study entry, background maternal demographic data, medical history, family history, obstetric history, medication intake through pregnancy, early pregnancy data, and any pregnancy complications are recorded. Paternal demographic data and height and weight are also recorded. Fetal ultrasound growth within 2 weeks before or 1 week after study entry is documented. During the study, women are asked to continue measuring capillary glucose levels fasting and 2 h after the start of each meal. These are performed on a Precision (now Optium) Medisense meter, which is downloaded each clinic visit and relevant readings are recorded in the database. At 36/37 weeks’ gestation, fasting maternal blood samples are taken for repeat measurement of A1C, glucose, and lipids; a urine albumin-to-creatinine ratio is measured, and a fetal growth scan is repeated. At delivery, pregnancy complications, indication for induction (if performed), mode of delivery, and complications are recorded from the hospital notes. Detailed neonatal morbidity is also recorded. Trained personnel perform anthropometric and blood pressure measurements on the baby within 48 h of birth. If consented, cord blood is stored for assessment of insulin and other markers of the adipoinsular axis. At 6–8 weeks’ postpartum, women and their infants are seen again. The woman's medications, weight, blood pressure, fasting triglyceride levels, and oral glucose tolerance test results are recorded. Details of the infant's feeding and health are documented and anthropometric measurements are repeated. Contact details are confirmed for women who consent to the follow-up of their offspring. The primary outcome is a composite of neonatal morbidity, including hypoglycemia (14% expected to have two results <2.6 mmol/l, 7% requiring intravenous dextrose), respiratory distress (estimate 5%), phototherapy (5%), birth trauma (1.5%), low 5-min Apgar (<7, <1%), and prematurity (15%). The protocol for monitoring for hypoglycemia is based on the Auckland Newborn Services Guidelines (31). Neonatal hypoglycemia is defined as a capillary glucose level <2.6 mmol/l. In addition, recurrent glucose levels <2.6 mmol/l and any levels <1.6 mmol/l are recorded. Treatment of hypoglycemia and duration of treatment is detailed. Respiratory distress is recorded if an infant requires ≥4 h of respiratory support in the first 24 h after delivery. Again, duration of support and diagnosis are recorded. Birth trauma is classified as minor, moderate, or severe according to subsequent recovery, with detailed definitions in the study manual. In brief, it is mild if resolved by 6 weeks postpartum, moderate if expected to recover within 3 months, and severe if long-term impact on function is anticipated. Admission to level 2 or 3 neonatal nursery and duration of stay is recorded as another way of capturing neonatal morbidity. Secondary outcome measures include the following: maternal glycemia control, neonatal body composition and other markers of neonatal insulin sensitivity including cord blood assays, maternal hypertensive complications as defined by the Australasian Society for Study of Hypertension in Pregnancy (32), maternal postpartum glucose tolerance, and acceptability of treatments by questionnaire. With respect to maternal glycemia, there are data entry points for every fasting and 2-h postprandial glucose level so that details of control and testing compliance can be assessed. Neonatal body composition is assessed from anthropometric measurements, which include crown heel and crown rump lengths using a Harpenden neonatometer. Circumference measurements of head, mid–upper arm, chest, and waist are performed to the nearest 0.1 cm according to guidelines outlined in the study manual. Subscapular and triceps skinfold thickness is measured to the nearest 0.2 mm using a Holtain or Harpenden caliper. Study personnel are trained and have regular review of technique at each site. Cord blood samples are collected in a 30-ml syringe after clamping of the cord and are placed into EDTA and plain tubes. Samples are sent directly to the laboratory for processing within 10 min of collection or stored on ice to be processed within 90 min. Samples are centrifuged and plasma and serum aliquots are stored in 1-mm nunc tubes in a −80° freezer for later use. Acceptability of treatments is assessed by a short questionnaire that is administered to the woman after her baby has been measured and within a week of delivery. There are five questions that ask about which medication she had, how often she forgot medication, medication preferences in a subsequent pregnancy, and how adherence to medication compared with adherence to diet and glucose monitoring. Adverse events are reported routinely through the study datasheets or immediately if they are severe. A data safety monitoring committee reviews all serious adverse events at the time they are reported and provides recommendations to the principal investigators. The data safety monitoring committee has reviewed an interim analysis of 200 women and will be reviewing an analysis of ∼500 women by the end of 2005. The Green Lane Coordinating Centre, Auckland, is involved with several aspects of the study, including data management, site monitoring, and statistical support. Randomization is performed and data are entered on an Oracle version web-based database, which uses Secured Socket Layer 128 bit for data transmission security. Monitors initially check 25% of data entries at each site and subsequently 10% if data entries are accurate and the site satisfies good clinical practice guidelines.

49 Resultados del estudio MiG
The primary outcome is a composite of neonatal morbidity, including hypoglycemia (14% expected to have two results <2.6 mmol/l, 7% requiring intravenous dextrose), respiratory distress (estimate 5%), phototherapy (5%), birth trauma (1.5%), low 5-min Apgar (<7, <1%), and prematurity (15%). The protocol for monitoring for hypoglycemia is based on the Auckland Newborn Services Guidelines (31). Neonatal hypoglycemia is defined as a capillary glucose level <2.6 mmol/l. In addition, recurrent glucose levels <2.6 mmol/l and any levels <1.6 mmol/l are recorded. Treatment of hypoglycemia and duration of treatment is detailed. Respiratory distress is recorded if an infant requires ≥4 h of respiratory support in the first 24 h after delivery. Again, duration of support and diagnosis are recorded. Birth trauma is classified as minor, moderate, or severe according to subsequent recovery, with detailed definitions in the study manual. In brief, it is mild if resolved by 6 weeks postpartum, moderate if expected to recover within 3 months, and severe if long-term impact on function is anticipated. Admission to level 2 or 3 neonatal nursery and duration of stay is recorded as another way of capturing neonatal morbidity. Secondary outcome measures include the following: maternal glycemia control, neonatal body composition and other markers of neonatal insulin sensitivity including cord blood assays, maternal hypertensive complications as defined by the Australasian Society for Study of Hypertension in Pregnancy (32), maternal postpartum glucose tolerance, and acceptability of treatments by questionnaire. With respect to maternal glycemia, there are data entry points for every fasting and 2-h postprandial glucose level so that details of control and testing compliance can be assessed. Neonatal body composition is assessed from anthropometric measurements, which include crown heel and crown rump lengths using a Harpenden neonatometer. Circumference measurements of head, mid–upper arm, chest, and waist are performed to the nearest 0.1 cm according to guidelines outlined in the study manual. Subscapular and triceps skinfold thickness is measured to the nearest 0.2 mm using a Holtain or Harpenden caliper. Study personnel are trained and have regular review of technique at each site. Cord blood samples are collected in a 30-ml syringe after clamping of the cord and are placed into EDTA and plain tubes. Samples are sent directly to the laboratory for processing within 10 min of collection or stored on ice to be processed within 90 min. Samples are centrifuged and plasma and serum aliquots are stored in 1-mm nunc tubes in a −80° freezer for later use. Acceptability of treatments is assessed by a short questionnaire that is administered to the woman after her baby has been measured and within a week of delivery. There are five questions that ask about which medication she had, how often she forgot medication, medication preferences in a subsequent pregnancy, and how adherence to medication compared with adherence to diet and glucose monitoring. Adverse events are reported routinely through the study datasheets or immediately if they are severe. A data safety monitoring committee reviews all serious adverse events at the time they are reported and provides recommendations to the principal investigators. The data safety monitoring committee has reviewed an interim analysis of 200 women and will be reviewing an analysis of ∼500 women by the end of 2005. The Green Lane Coordinating Centre, Auckland, is involved with several aspects of the study, including data management, site monitoring, and statistical support. Randomization is performed and data are entered on an Oracle version web-based database, which uses Secured Socket Layer 128 bit for data transmission security. Monitors initially check 25% of data entries at each site and subsequently 10% if data entries are accurate and the site satisfies good clinical practice guidelines. Statistical procedures It was decided that an increase in neonatal morbidity from 30% (based on annual Auckland clinic data) to 40% would be required to reject the hypothesis that women treated with metformin will have similar neonatal morbidity to women treated with insulin. Using two-tailed calculations with a power of 80% and significance at <0.05, the study requires 375 women in each arm. The trial is also powered to address individual components of morbidity (e.g., neonatal hypoglycemia). Women will be analyzed on an intention-to-treat basis. Between-group comparison will be done using a t test or ANOVA where appropriate, or Mann-Whitney U test or Kruskal-Wallis where the data are not normally distributed. For categorical data, χ2 test (with Yates’ correction or Fisher's exact test where appropriate) will be used. The continuous results will be expressed as means and SDs or medians and interquartile ranges according to the data distribution, and categorical data will be presented as proportions with 95% CIs. Generalized linear models will be used to perform multivariate analysis to allow the comparison of groups while controlling for possible confounding variables. A logistic regression model for dichotomous outcomes will be used. As there are multiple associated outcomes, care will be exercised in the interpretation of the results. For the analyses reported, SAS 9.1 (SAS Institute, Cary, NC) has been

50 Resultados Estudio MiG

51 Resultados Estudio MiG
Metformin no se asoció con aumento de complicaciones perinatales comparado con el grupo de Insulina Las pacientes prefieren metformin a insulina

52 Tratamiento Diabetes y Embarazo METFORMIN
recomendaciones Iniciar con dosis bajas: 425 o 500mg. en cada alimento Tomar precauciones para evitar gastritis Puede mantenerse esa dosis, si mantiene óptimo control

53 Tratamiento Diabetes y Embarazo
METFORMIN Valorar la respuesta en 2 semanas Incrementar dosis en pacientes con Obesidad ( IMC >30 ) No suspenderlo

54 Programa Diabetes y Embarazo 786 pacientes

55 Programa Diabetes y Embarazo

56 Conclusión de Tx. METFORMIN
mejores resultados con la combinación de Dieta y ejercicio Metformin

57 Los cielos y la Tierra pasarán, pero mi palabra, no pasará
Mateo 24:35 Conclusiones

58 Pensar en DMG Hacer las pruebas dx Establecer el dx Iniciar el tratamiento Reducir morbilidad perinatal

59 G r a c i a s !!

60 Los cielos y la Tierra pasarán, pero mi palabra, no pasará
Mateo 24:35 Diabetes Gestacional Actualidades 2013