Der Gestationsdiabetes ist eine der häufigsten Erkrankungen in der Schwangerschaft. Obwohl der Zusammenhang zwischen den Blutzuckerwerten und der Morbidität der Schwangeren und des Kindes hinreichend belegt ist, gibt es bemerkenswert viele klinisch relevante Fragen, die bisher nur unzureichend untersucht wurden. Die vorliegende Arbeit beschäftigt sich mit einigen Fragestellungen aus diesem Themenbereich, unter Einbeziehung einer neuen Methode der Glukosemessung, der kontinuierlichen Glukosemessung. In Deutschland wird in der Schwangerschaft lediglich ein Urin-Stix als Screening-Methode auf Gestationsdiabetes durchgeführt. Die wenigen Publikationen, die sich mit der Sensitivität des Urin-Stix zur Detektion des Gestationsdiabetes beschäftigen, zeigen eine nur geringe Sensitivität. Die in unserem Hause durchgeführte Untersuchung an 1001 Schwangeren bestätigt die bisherigen Ergebnisse an einer großen Fallzahl und weist zudem noch eine deutliche Abhängigkeit der Glukosurie-Rate von den diastolischen Blutdruckwerten nach. Eine weitere Untersuchung wurde zu dem 50-g-Glukose-Screeningtests durchgeführt, den wir seit 1993 routinemäßig bei allen Schwangeren durchführen, die sich in unserer Klinik vorstellen. Mit einer Sensitivität und Spezifität von ca. 90% - bezogen auf den oralen Glukosetoleranztest - zeigte dieser Test ein gutes Ergebnis, allerdings fanden wir heraus, dass die Rate positiver Ergebnisse von dem Zeitpunkt der vorangegangenen Mahlzeit abhängig ist und zwischen 11%-40% liegt. Bisher konnte kein Nachweis erbracht werden, dass die einem oralen Glukosetoleranztest (oGTT) vorangehende Kohlenhydratzufuhr bei Schwangeren einen Einfluss auf die Ergebnisse hat, wie es die Empfehlungen der Fachgesellschaften vermuten. In der von uns durchgeführten Studie, bei der wir - im Gegensatz zu den anderen Studien - detallierte Ernährungsprotokolle verwendeten, konnte diese Vermutung bestätigt werden. Aufgrund erhöhter Konzentrationen an Gestagen, Östrogenen und dem humanen Plazentalaktogen wurde häufig vermutet, dass Schwangere mit Gemini eher einen Gestationsdiabetes haben müssten. Wir konnten dies in einer Matched-Pair-Studie widerlegen. Die kontinuierliche Glukosemessung erlaubte neue Einblicke in die Physiologie und Pathophysiologie der Schwangerschaft. Nachdem wir zunächst ein Auswertungsverfahren etabliert hatten, wurden Schwangere mit und ohne Glukosetoleranzstörung mit Hilfe des kontinuierlichen Glukosemonitors der Fa. MedtronicMinimed (CGMS) untersucht. Es zeigte sich, dass das CGMS eine deutlich bessere Differenzierung zwischen den Gesunden und den Schwangeren mit eingeschränkter Glukosetoleranz ermöglichte, dies im Gegensatz zum konventionellen Blutzuckertagesprofil. In einer weiteren Auswertung untersuchten wir den Zusammenhang zwischen der mütterlichen sowie der neonatalen Morbidität und den einzelnen postprandialen Messzeitpunkten. Es zeigten sich signifikante Unterschiede der Glukosewerte für die Schwangerschaftsausgangsparameter Entbindungsmodus, Makrosomie und fetale Verlegungsrate im postprandialen Zeitintervall von 45-105 Minuten. Erstmalig konnten wir so die Assoziation zwischen neonatalen Morbiditäten und den postprandialen Glukosekonzentrationen zu verschiedenen Messzeitpunkten nachweisen. / Gestational diabetes is the most common complication during pregnancies. Although the correlation has been clearly established between blood glucose levels and morbidity rates for both mothers and babies, there are surprisingly many clinically relevant questions that still have not been adequately addressed. The study presented here investigates some aspects of this topic, using a new method for measuring blood sugar levels, continuous glucose measurement. In Germany, the only screening method normally used to test pregnant women for gestational diabetes is a urine test strip. The few publications that deal with the sensitivity of urine test strips for detecting gestational diabetes show only minimal sensitivity. The study carried out in our clinic with a large number of test cases (1001 pregnant women) confirmed previous findings and demonstrates that the glucosuria rate directly corresponds to diastolic blood pressure values. An additional appraisal was made of the 50-gram glucose screening tests which we have routinely carried out on all pregnant women visiting our clinic since 1993. With a sensitivity and specificity of approx. 90% - as compared to the oral glucose test – this screening method yielded good results; however, we did notice that the interval since the most recent meal influences the positive outcome rate, which ranges from 11 % - 40 %. Up to the present, no one has been able to prove that eating carbohydrates before an oral glucose tolerance test (oGTT) influences the results, a belief often found in experts’ recommendations for pregnant women. However, our study, in which the pregnant women – unlike other studies – kept detailed food journals, did indeed confirm this hypothesis. Based on the higher concentrations of gestagen, estrogen and the human placenta lactogen, researchers often presume that mothers carrying twins are more likely than other expectant mothers to have gestational diabetes. Using a matched-pair-study, we refuted this idea. Continuous glucose testing allows new insights into the physiology and pathophysiology of pregnancy. After establishing an analytical procedure, we examined pregnant women both with and without glucose tolerance dysfunction using the continuous glucose monitors (CGMS) made by MedtronicMinimed. We demonstrated that the CGMS - as opposed to a conventional daily log of blood glucose values - provided markedly better differentiation between healthy women and those with impaired glucose tolerance. In a further analytical step, we studied the correlation between postprandial testing intervals and maternal and infant morbidity rates. Corresponding to the pregnancy parameters birth method, macrosomia and fetal transferral rate, significant differences were seen when glucose levels monitored 45 - 105 minutes after a meal were compared. For the first time, it was possible to demonstrate a clear correlation between postprandial glucose concentrations checked at various intervals and neonatal morbidity.

Objetivo: O objetivo desse estudo foi identificar a associação entre fatores clínicos e laboratoriais com o uso de insulina em gestantes com DMG no momento do diagnóstico e analisar os possíveis fatores preditores do uso de insulina. Método: Foram estudadas, de forma retrospectiva, 294 pacientes com diabetes melito gestacional (DMG) diagnosticado por meio do teste de tolerância à glicose oral de 100 gramas (TTGO-100g) entre 24 e 33 semanas completas de gestação, cujo seguimento pré-natal foi realizado ambulatorialmente pelo setor de Endocrinopatias e Gestação da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1 de julho de 2002 a 30 de junho de 2008. Os seguintes fatores clínicos e laboratoriais, que pudessem estar associados ao uso de insulina para controle glicêmico, foram analisados: idade materna, obesidade pré-gestacional - índice de massa corpórea (IMC) > 30 Kg/m2, antecedente familiar de diabetes melito (DM), tabagismo, hipertensão arterial, uso de corticosteróides sistêmicos, antecedente obstétrico de DMG e de macrossomia fetal, nuliparidade, multiparidade, antecedente obstétricos de natimortos e neomortos, idade gestacional no momento do diagnóstico, gemelidade, índice de líquido amniótico (ILA) aumentado ILA > 18 cm, polidrâmnio (ILA > 25 cm), número de valores anormais do TTGO-100g, glicemia de jejum anormal no TTGO- 100g glicemia de jejum > 95 mg/dL; média das quatro glicemias aferidas no TTGO-100g; valor da glicemia de jejum, de 1ª, 2ª e 3ª horas do TTGO-100g e hemoglobina glicada (HbA1c). A associação entre cada fator e a necessidade de insulinoterapia foi analisada individualmente (2 de Pearson / teste exato de Fisher e teste t de Student). O modelo de regressão logística para a análise multivariada foi usado para predizer a probabilidade desses fatores em relação ao uso de insulina. Resultados: Das 294 pacientes avaliadas, 39,8% (117/294) necessitaram de insulinoterapia para controle glicêmico. Observou-se correlação positiva entre o uso de insulina e obesidade pré-gestacional, antecedente familiar de DM, hipertensão arterial, antecedente obstétrico de DMG e de macrossomia fetal, número de valores anormais no TTGO-100g, glicemia de jejum > 95 mg/dL no TTGO-100g; média das quatro glicemias aferidas no TTGO-100g; valor da glicemia de jejum, de 1ª, 2ª e 3ª horas do TTGO-100g e HbA1c pela análise univariada (P<0,05). Na análise do modelo de regressão logística foram desenvolvidos dois modelos que incluíam os seguintes fatores preditores do uso de insulina: obesidade pré-gestacional, antecedente familiar de DM, número de valores anormais no TTGO-100g (só modelo 1) e valor da glicemia de jejum do TTGO-100g (só modelo 2). Os dois primeiros modelos foram novamente analisados, incluindo-se a variável HbA1c para verificação de sua contribuição na predição do uso de insulina. Curvas de probabilidade e escores foram construídos com base nas quatro combinações de fatores preditores. Conclusões: É possível estimar a probabilidade do uso de insulinoterapia para controle glicêmico em gestantes com DMG por meio de IMC pré-gestacional, antecedente familiar de DM, número de valores anormais do TTGO-100g, valor da glicemia de jejum no TTGO-100g e da HbA1c. / Objective: To determine the association between clinical and laboratory parameters and insulin requirement in pregnancies complicated by gestational diabetes mellitus (GDM), and to evaluate possible factors predicting the need for insulin therapy. Methods: A total of 294 patients with GDM diagnosed by the 100- g/3-h oral glucose tolerance test (OGTT) between 24 and 33 complete weeks of gestation were retrospectively studied. These patients were under prenatal follow-up at the Obstetric Clinic of the University of Sao Paulo School of Medicine (HCFMUSP) between July 1, 2002 and June 30, 2008. The clinical and laboratory factors which could be associated to the need for insulin therapy were analyzed: maternal age, prepregnancy obesity body mass index (BMI) > 30 Kg/m2, family history of diabetes mellitus (DM), smoking, hypertension, use of systemic corticosteroids, prior GDM, prior fetal macrosomia, nulliparity, multiparity, prior stillbirth, prior neonatal death, gestational age at diagnosis of GDM, multiple pregnancy, elevated amniotic fluid index (AFI) AFI > 18 cm, polyhydramnios (AFI > 25 cm), number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose > 95 mg/dL, mean of the four 100-g/3-h OGTT values, 100-g/3-h OGTT fasting/one/two/three plasma glucose values, and glycated hemoglobin (HbA1c). The association between each factor and the need for insulin therapy was then analyzed individually (Pearsons chi-square/Fishers exact or Student t test). The performance of these factors to predict the probability of insulin therapy was estimated using a logistic regression model. Results: Among the 294 patients studied, 39.8% (117/294) required insulin for glycemic control. Univariate analysis showed a positive correlation between insulin therapy and prepregnancy obesity, family history of diabetes, hypertension, prior GDM, prior fetal macrosomia, number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose > 95 mg/dL, mean of the four 100-g/3-h OGTT values, 100-g/3-h OGTT fasting/one/two/three plasma glucose values, and HbA1c (P < 0.05). Two logistic regression models were developed and included the following parameters: prepregnancy obesity, family history of diabetes, number of abnormal 100-g/3-h OGTT values (just model 1) and 100-g/3-h OGTT fasting plasma glucose (just model 2). The two first models were analysed another time including the variable HbA1c to verify its contribution on prediction of the need for insulin therapy. Probability curves and scores were constructed based on the four combinations of predictive factors. Conclusions: The probability of insulin therapy can be estimated in pregnant women with GDM based on prepregnancy obesity, family history of diabetes, number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose, and HbA1c concentration.

Submitted by Rosivalda Pereira (mrs.pereira@ufma.br) on 2017-09-04T19:38:44Z No. of bitstreams: 1 MariaGloriaTavares.pdf: 1578457 bytes, checksum: d6ddc32a3c245b3f67f5abd4e4158ad0 (MD5) / Made available in DSpace on 2017-09-04T19:38:44Z (GMT). No. of bitstreams: 1 MariaGloriaTavares.pdf: 1578457 bytes, checksum: d6ddc32a3c245b3f67f5abd4e4158ad0 (MD5) Previous issue date: 2017-07-07 / Gestational Diabetes Mellitus (GDM) is classified as glucose intolerance, whose onset or detection occurs during pregnancy. One of the ways to identify GDM is 75g oral glucose tolerance test. According to the International Diabetes and Pregnancy Association Study Group(IADPSG), GDM is diagnosed when at least 1 of the three curve points are greater than or equal to 92, 180 and 153 mg / dl at time 0 , 1 and 2 hours respectively. A characteristic of this criterion is the diagnosis based on a single altered value. However, the mechanisms involved in impaired fasting glucose (IFG) are different from those found in impaired glucose tolerance (IGT) after oral glucose tolerance test (OGTT). So, differences in pregnancy outcomes are possible according to OGTT behavior. This work had as general objective to categorize pregnant women diagnosed with GDM, using the IADPSG criteria, according to the type of glycemic alteration found in the OGTT results, and to correlate with fetal weight birth. In order to do so, the cases of DMG treated at the University Hospital of the Federal University of Maranhão, from December 2013 to December 2015, were divided into 3 groups, according to the alterations found in the glycemic curve of the OGTT (Group 1: IFG isolated, Group 2: IGT only, Group 3: IFG and IGT). A total of 89 patients were studied, the majority belonging to groups 3 (54%). This same group had the highest glycemic averages at diagnosis and during follow-up, being the group with the highest occurrence of newborns large for gestational age (LGA), with 39.6%. Then group 1 with an occurrence of 27.3% of newborns LGAs. It was concluded that, as pregnant women with DMG with altered fasting glycemia in the OGTT, especially those with associated glucose intolerance, presented a higher risk for newborns large for gestational age. / Diabetes Mellitus Gestacional (DMG) é classicamente definido como intolerância à glicose de gravidade variável, cujo início ou detecção ocorre durante a gravidez. Uma das formas de rastreá-la é através da curva glicêmica após sobrecarga oral de glicose, com 75g de dextrosol. Segundo o critério do International Association of Diabetes and Pregnancy Study Group (IADPSG), considera-se diagnóstico de DMG quando pelo menos um dos três pontos da curva encontra-se maior ou igual a 92, 180 e 153 mg/dl, nos tempos 0, 1, 2 horas respectivamente. Uma característica deste critério, é o diagnóstico baseado em apenas um único valor alterado, seja ele em jejum ou após a sobrecarga. No entanto, os mecanismos que levam à alteração da glicemia jejum (GJA) são diferentes daqueles encontrados na intolerância à glicose (ITG) após sobrecarga de glicose. Sendo assim, acredita-se poder haver diferenças, em relação aos desfechos fetais, a depender do perfil encontrado na curva glicêmica das gestantes com diagnóstico de DMG. Este trabalho teve como objetivo geral categorizar as gestantes diagnosticadas com DMG pelo teste de tolerância oral à glicose (TTOG), utilizando o critério do IADPSG, de acordo com o tipo de alteração glicêmica encontrada na curva de sobrecarga, e correlacionar com o peso fetal ao nascimento. Para isso, foram revisados os casos de DMG atendidos no Hospital Universitário da Universidade Federal do Maranhão (HUUFMA), no período de dezembro de 2013 a dezembro de 2015, estes foram divididos em 3 grupos, de acordo com as alterações encontradas na curva glicêmica do TOTG (Grupo 1: GJA isoladamente; Grupo 2: ITG isoladamente, Grupo 3: GJA e ITG). Foram estudadas 89 pacientes, a maioria pertencente ao grupo 3 (54%). Este mesmo grupo apresentou as médias glicêmicas mais elevadas ao diagnóstico e durante o seguimento, sendo o grupo com maior ocorrência de recém-nascidos grandes para idade gestacional (GIG), com 39,6%. Em seguida o grupo 1 com uma ocorrência de 27,3% de recém nascidos GIGs. Concluiu-se que as gestantes com DMG com alteração na glicemia de jejum no TTOG, principalmente aquelas com intolerância à glicose associada, apresentaram maior risco para recém-nascidos grandes para idade gestacional.

Objetivo: O objetivo desse estudo foi identificar a associação entre fatores clínicos e laboratoriais com o uso de insulina em gestantes com DMG no momento do diagnóstico e analisar os possíveis fatores preditores do uso de insulina. Método: Foram estudadas, de forma retrospectiva, 294 pacientes com diabetes melito gestacional (DMG) diagnosticado por meio do teste de tolerância à glicose oral de 100 gramas (TTGO-100g) entre 24 e 33 semanas completas de gestação, cujo seguimento pré-natal foi realizado ambulatorialmente pelo setor de Endocrinopatias e Gestação da Clínica Obstétrica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de 1 de julho de 2002 a 30 de junho de 2008. Os seguintes fatores clínicos e laboratoriais, que pudessem estar associados ao uso de insulina para controle glicêmico, foram analisados: idade materna, obesidade pré-gestacional - índice de massa corpórea (IMC) > 30 Kg/m2, antecedente familiar de diabetes melito (DM), tabagismo, hipertensão arterial, uso de corticosteróides sistêmicos, antecedente obstétrico de DMG e de macrossomia fetal, nuliparidade, multiparidade, antecedente obstétricos de natimortos e neomortos, idade gestacional no momento do diagnóstico, gemelidade, índice de líquido amniótico (ILA) aumentado ILA > 18 cm, polidrâmnio (ILA > 25 cm), número de valores anormais do TTGO-100g, glicemia de jejum anormal no TTGO- 100g glicemia de jejum > 95 mg/dL; média das quatro glicemias aferidas no TTGO-100g; valor da glicemia de jejum, de 1ª, 2ª e 3ª horas do TTGO-100g e hemoglobina glicada (HbA1c). A associação entre cada fator e a necessidade de insulinoterapia foi analisada individualmente (2 de Pearson / teste exato de Fisher e teste t de Student). O modelo de regressão logística para a análise multivariada foi usado para predizer a probabilidade desses fatores em relação ao uso de insulina. Resultados: Das 294 pacientes avaliadas, 39,8% (117/294) necessitaram de insulinoterapia para controle glicêmico. Observou-se correlação positiva entre o uso de insulina e obesidade pré-gestacional, antecedente familiar de DM, hipertensão arterial, antecedente obstétrico de DMG e de macrossomia fetal, número de valores anormais no TTGO-100g, glicemia de jejum > 95 mg/dL no TTGO-100g; média das quatro glicemias aferidas no TTGO-100g; valor da glicemia de jejum, de 1ª, 2ª e 3ª horas do TTGO-100g e HbA1c pela análise univariada (P<0,05). Na análise do modelo de regressão logística foram desenvolvidos dois modelos que incluíam os seguintes fatores preditores do uso de insulina: obesidade pré-gestacional, antecedente familiar de DM, número de valores anormais no TTGO-100g (só modelo 1) e valor da glicemia de jejum do TTGO-100g (só modelo 2). Os dois primeiros modelos foram novamente analisados, incluindo-se a variável HbA1c para verificação de sua contribuição na predição do uso de insulina. Curvas de probabilidade e escores foram construídos com base nas quatro combinações de fatores preditores. Conclusões: É possível estimar a probabilidade do uso de insulinoterapia para controle glicêmico em gestantes com DMG por meio de IMC pré-gestacional, antecedente familiar de DM, número de valores anormais do TTGO-100g, valor da glicemia de jejum no TTGO-100g e da HbA1c. / Objective: To determine the association between clinical and laboratory parameters and insulin requirement in pregnancies complicated by gestational diabetes mellitus (GDM), and to evaluate possible factors predicting the need for insulin therapy. Methods: A total of 294 patients with GDM diagnosed by the 100- g/3-h oral glucose tolerance test (OGTT) between 24 and 33 complete weeks of gestation were retrospectively studied. These patients were under prenatal follow-up at the Obstetric Clinic of the University of Sao Paulo School of Medicine (HCFMUSP) between July 1, 2002 and June 30, 2008. The clinical and laboratory factors which could be associated to the need for insulin therapy were analyzed: maternal age, prepregnancy obesity body mass index (BMI) > 30 Kg/m2, family history of diabetes mellitus (DM), smoking, hypertension, use of systemic corticosteroids, prior GDM, prior fetal macrosomia, nulliparity, multiparity, prior stillbirth, prior neonatal death, gestational age at diagnosis of GDM, multiple pregnancy, elevated amniotic fluid index (AFI) AFI > 18 cm, polyhydramnios (AFI > 25 cm), number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose > 95 mg/dL, mean of the four 100-g/3-h OGTT values, 100-g/3-h OGTT fasting/one/two/three plasma glucose values, and glycated hemoglobin (HbA1c). The association between each factor and the need for insulin therapy was then analyzed individually (Pearsons chi-square/Fishers exact or Student t test). The performance of these factors to predict the probability of insulin therapy was estimated using a logistic regression model. Results: Among the 294 patients studied, 39.8% (117/294) required insulin for glycemic control. Univariate analysis showed a positive correlation between insulin therapy and prepregnancy obesity, family history of diabetes, hypertension, prior GDM, prior fetal macrosomia, number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose > 95 mg/dL, mean of the four 100-g/3-h OGTT values, 100-g/3-h OGTT fasting/one/two/three plasma glucose values, and HbA1c (P < 0.05). Two logistic regression models were developed and included the following parameters: prepregnancy obesity, family history of diabetes, number of abnormal 100-g/3-h OGTT values (just model 1) and 100-g/3-h OGTT fasting plasma glucose (just model 2). The two first models were analysed another time including the variable HbA1c to verify its contribution on prediction of the need for insulin therapy. Probability curves and scores were constructed based on the four combinations of predictive factors. Conclusions: The probability of insulin therapy can be estimated in pregnant women with GDM based on prepregnancy obesity, family history of diabetes, number of abnormal 100-g/3-h OGTT values, 100-g/3-h OGTT fasting plasma glucose, and HbA1c concentration.

<p>The high prevalence of diabetes mellitus among the Sudanese population is linked to obesity, poor glycaemic control and a high rate of complications. This study investigated 1/ Leptin hormone and its correlations with different biochemical characteristics in Sudanese diabetic subjects, 2/ The impact of glycaemic control on pregnancy outcome in pregnancies with diabetes, 3/ The glycaemic response to Sudanese traditional carbohydrate foods, 4/ The influence of glucose self-monitoring on the glycaemic control among this population, 5/ The health related quality of life in Sudanese subjects with diabetes-related lower limb amputation. </p><p>Leptin was significantly lower in diabetic subjects compared with controls of same BMI in both females (P =0.0001) and males (P =0.019). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =0.018) and insulin resistance (P =.038). In controls, leptin correlated only with insulin resistance. Pregnancy complications were higher among diabetic compared with control women (P<0.0001) and varied with the type of diabetes. Infants of diabetic mothers had a higher incidence of neonatal complications than those of non-diabetic women (P<0.0001). In six Sudanese traditional carbohydrate meals over all differences in incremental AUCs were significant for both plasma glucose (P = 0.0092) and insulin (P = 0.0001). Millet porridge and wheat pancakes displayed significantly lower post-prandial glucose and insulin responses, whereas maize porridge induced a higher post-prandial glucose and insulin response. In type 2 diabetic subjects SMBG or SMUG was not related to glycaemic control. In type 1 diabetic subjects, SMBG was significantly associated with better glycaemic control, as assessed by HbA1c (P=0.02) and blood glucose at clinic visits (P=<0.0001), similar associations were found for SMUG respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Diabetic subjects with LLA had significantly poorer HRQL compared to a reference diabetic group (P=<0.0001). Duration of diabetes and amputation had negative impact on HRQL in subjects with LLA (P=<0.0001) respectively. Diabetic subjects with LLA had decreased sense of coherence and high presence of symptoms. Improving health services at the primary level is important to reduce the complications and burden of disease in the Sudanese population.</p>

The high prevalence of diabetes mellitus among the Sudanese population is linked to obesity, poor glycaemic control and a high rate of complications. This study investigated 1/ Leptin hormone and its correlations with different biochemical characteristics in Sudanese diabetic subjects, 2/ The impact of glycaemic control on pregnancy outcome in pregnancies with diabetes, 3/ The glycaemic response to Sudanese traditional carbohydrate foods, 4/ The influence of glucose self-monitoring on the glycaemic control among this population, 5/ The health related quality of life in Sudanese subjects with diabetes-related lower limb amputation. Leptin was significantly lower in diabetic subjects compared with controls of same BMI in both females (P =0.0001) and males (P =0.019). In diabetic subjects, serum leptin correlated positively with the homeostatic assessment (HOMA) of both beta-cell function (P =0.018) and insulin resistance (P =.038). In controls, leptin correlated only with insulin resistance. Pregnancy complications were higher among diabetic compared with control women (P&lt;0.0001) and varied with the type of diabetes. Infants of diabetic mothers had a higher incidence of neonatal complications than those of non-diabetic women (P&lt;0.0001). In six Sudanese traditional carbohydrate meals over all differences in incremental AUCs were significant for both plasma glucose (P = 0.0092) and insulin (P = 0.0001). Millet porridge and wheat pancakes displayed significantly lower post-prandial glucose and insulin responses, whereas maize porridge induced a higher post-prandial glucose and insulin response. In type 2 diabetic subjects SMBG or SMUG was not related to glycaemic control. In type 1 diabetic subjects, SMBG was significantly associated with better glycaemic control, as assessed by HbA1c (P=0.02) and blood glucose at clinic visits (P=&lt;0.0001), similar associations were found for SMUG respectively. Neither glycaemic control nor glucose self-monitoring was associated with education level. Diabetic subjects with LLA had significantly poorer HRQL compared to a reference diabetic group (P=&lt;0.0001). Duration of diabetes and amputation had negative impact on HRQL in subjects with LLA (P=&lt;0.0001) respectively. Diabetic subjects with LLA had decreased sense of coherence and high presence of symptoms. Improving health services at the primary level is important to reduce the complications and burden of disease in the Sudanese population.

Obesity is a major health problem in the Western world. Mean birth weight has increased during the last 25 years. One explanation is that the proportion of large for gestational age (LGA) infants has increased. Such infants risk developing obesity, cardiovascular disease and diabetes later in life. Despite the risk of neonatal hypoglycemia, their postnatal metabolic adaptation has not been investigated. Our data, obtained with stable isotope labeled compounds, demonstrate that newborn LGA infants have increased lipolysis and decreased insulin sensitivity. After administration of glucagon, the plasma levels of glucose and the rate of glucose production increased. The simultaneous increase in insulin correlated with the decrease in lipolysis, indicating an antilipolytic effect of insulin in these infants. We also demonstrated an intergenerational effect of being born LGA, since women born LGA, were at higher risk of giving birth to LGA infants than women not born LGA. Further, the LGA infants formed three subgroups: born long only, born heavy only, and born both long and heavy. Infants born LGA of women with high birth weight or adult obesity were at higher risk of being LGA concerning weight alone, predisposing to overweight and obesity at childbearing age. In addition we found that pregnant women with gestational diabetes were at increased risk of giving birth to infants that were heavy alone. This could explain the risk of both perinatal complications and later metabolic disease in infants of this group of women. To identify determinants of fetal growth, 20 pregnant women with a wide range of fetal weights were investigated at 36 weeks of gestation. Maternal fat mass was strongly associated with insulin resistance. Insulin resistance was related to glucose production, which correlated positively with fetal size. The variation in resting energy expenditure, which was closely related to fetal weight, was largely explained by BMI, insulin resistance, and glucose production. Lipolysis was not rate limiting for fetal growth in this group of women. Consequently, high maternal glucose production due to a high fat mass may result in excessive fetal growth.

Abstract Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5–15% of women of reproductive age. The syndrome is characterized by menstrual irregularities, hyperandrogenism and polycystic ovaries. Infertility is a major problem in PCOS and it can be explained partially by chronic anovulatory cycles. Excess body weight and insulin resistance are common among women with PCOS, exposing them to the most common pregnancy complication, gestational diabetes mellitus (GDM) and, later in life, to a higher risk of developing glucose metabolism disorders eventually leading to outbreak of type 2 diabetes mellitus (T2DM). However, the respective roles of the syndrome per se, excess body weight and hyperandrogenism regarding the aforementioned complications are still to be clarified. The objectives were first to determine the risks of PCOS, infertility problems and decreased fertility at age 26 in women with a history of menstrual irregularity or elevated androgen levels in adolescence (at age 16). We also aimed to clarify whether PCOS per se is associated with decreased fertility and increased incidence of miscarriage, GDM, prediabetes and T2DM. Lastly, we focused on the respective roles of excess body weight and hyperandrogenism as regards the development of GDM and impaired glucose metabolism. The study populations were derived from the prospective Northern Finland Birth Cohorts 1966 and 1986, comprising all expected births in 1966 (n = 5889 females) and 1986 (n = 4567) in the two northernmost provinces of Finland. The data was complemented with fertility rates and diagnoses of GDM and T2DM from registers held by the National Institute for Health and Welfare and The Social Insurance Institution of Finland. Menstrual irregularity or elevated androgen levels in adolescence were associated at age 26 with increased risks of PCOS and infertility problems, but not with decreased fertility rates. At the end of their reproductive life women with symptoms of PCOS were not more often childless, had had a similar incidence of miscarriages but had a smaller family size compared with healthy women, and obesity further decreased family size in this group. Excess body weight and elevated androgen levels, but not PCOS per se, were independent risk factors of GDM. The increased risk of T2DM in PCOS was mainly due to excess body weight, although both factors had a synergistic effect on the development of T2DM. / Tiivistelmä Monirakkulainen munasarjaoireyhtymä (PCOS) on yleinen naisilla esiintyvä hormonaalinen häiriö, josta kärsii 5-15% lisääntymisikäisistä naisista. Kuukautiskierron häiriöt, mieshormoniylimäärä ja monirakkulaiset munasarjat ovat ominaisia oireyhtymälle. Lapsettomuus on keskeinen ongelma oireyhtymässä, mikä johtuu osittain kroonisesta ovulaatioiden epäsäännöllisyydestä tai niiden puuttumisesta. Ylipainoa ja insuliiniresistenssiä esiintyy usein oireyhtymää sairastavilla naisilla ja ne altistavat raskausajan diabeteksen puhkeamiselle. Myöhemmällä iällä PCOS-naisilla on suurentunut riski sairastua sokeriaineenvaihdunnan häiriöihin, jotka lisäävät riskiä tyypin 2 diabeteksen (T2DM) puhkeamiselle. PCOS:n, ylipainon ja mieshormoniylimäärän itsenäiset roolit edellä mainittujen häiriöiden kehittymisessä ovat kuitenkin edelleen epäselviä. Ensimmäisenä tavoitteena oli selvittää PCOS:n, lapsettomuusongelmien ja alentuneen hedelmällisyyden riskiä 26-vuotiaana naisilla, joilla todettiin kuukautiskierron häiriö tai kohonneet mieshormonipitoisuudet nuoruusiällä (16-vuotiaana). Toiseksi selvitimme, liittyykö PCOS itsessään alentuneeseen hedelmällisyyteen sekä kohonneeseen keskenmenojen, raskausdiabeteksen, diabeteksen esiasteiden ja T2DM esiintyvyyteen. Lisäksi selvitimme ylipainon ja mieshormoniylimäärän itsenäisiä rooleja raskausdiabeteksen ja muiden sokeriaineenvaihdunnan häiriöiden kehittymisessä. Tutkimusaineistoina olivat Pohjois-Suomen syntymäkohortit 1966 (n = 5889 naista) ja 1986 (n = 4567 naista), joihin sisältyivät kaikki elävänä syntyneet lapset vuosina 1966 ja 1986 kahdesta Suomen pohjoisimmasta läänistä. Tutkimusaineistoja täydennettiin hedelmällisyyslukujen ja GDM- sekä T2DM-diagnoosien osalta Terveyden ja hyvinvoinnin laitoksen ja Kansaneläkelaitoksen ylläpitämistä rekistereistä. Nuoruusiän kuukautiskierron häiriöt ja mieshormoniylimäärä olivat yhteydessä suurentuneeseen riskiin kehittää PCOS ja kärsiä lapsettomuusongelmista, mutta näiden yhteyttä alentuneisiin hedelmällisyyslukuihin 26-vuotiaana ei todettu. PCOS-oireiset naiset eivät kärsineet lapsettomuudesta lisääntymisiän aikana verrokkinaisia enemmän ja keskenmenojen esiintyvyys ei eronnut oireisten ja terveiden naisten välillä. Oireisilla naisilla oli kuitenkin pienempi perhekoko kuin verrokeilla, ja lihavuus entisestään pienensi perhekokoa oireisilla naisilla. Ylipaino ja mieshormoniylimäärä olivat itsenäisiä riskitekijöitä raskausdiabeteksen kehittymiselle. PCOS ei ollut riskitekijä raskausdiabeteksen kehittymiselle. Kohonnut T2DM-riski PCOS:ssa johtui lähinnä ylipainosta, vaikkakin molemmat tekijät olivat itsenäisiä riskitekijöitä T2DM:n kehittymiselle.

Les relations bien connues en cas d'hémochromatose entre surcharge en fer, insulinorésistance et stress oxydant, nous ont conduit à chercher à établir le rôle de la ferritine comme un facteur prédictif du risque de diabète gestationnel et du stress oxydant indépendamment de toute supplémentation dans une population de femmes Libanaises non anémiques. Nous avons observé qu'une ferritine élevée en début de la grossesse était un facteur prédictif d'intolérance au glucose, alors que cette relation n'était pas retrouvée avec une hémoglobine élevée, suggérant que le fer de réserve est un facteur de risque à considérer et non pas le fer fonctionnel. Le dosage de la ferritine pourrait être un marqueur biologique à prendre en considération pour évaluer le risque d'intolérance au glucose chez les femmes à risque de diabète gestationnel. La prévalence du diabète gestationnel dans la population étudiée, sur la base de nouveaux critères adoptés par l'Organisation mondiale de la santé était de ~15% alors qu'elle n'était que de 4% avec les critères de O'Sullivan actuellement utilisés dans les hôpitaux où a été recrutée notre population. Cette forte différence souligne la nécessité de l'adoption de nouveaux critères pour un meilleur dépistage et une meilleure prise en charge du fait des risques materno-fœtaux associés au diabète gestationnel. Malgré l'abaissement des valeurs de la glycémie, nous montrons que les nouveaux seuils de glycémie définissant désormais un diabète gestationnel sont toujours associés à une augmentation du stress oxydant, notamment des dommages à l'ADN. Conformément à la littérature, nous montrons qu'un statut en fer élevé, est associé à un état de stress oxydant élevé. De façon plus originale nous montrons qu'une ferritine élevée en début de grossesse aggrave l'association du stress oxydant et de l'insulinorésistance avec l'intolérance au glucose. En l`absence de modèle satisfaisant pour l`étude du diabète gestationnel expérimental, nous avons validé dans une étude préliminaire un régime riche en fructose comme modèle expérimental de diabète gestationnel. Nous montrons que ce modèle induit les mêmes modifications chez les rates et leurs ratons que celles observées lors de diabète gestationnel, de plus lorsque ce régime est enrichi en fer, des altérations oxydatives sont observées au niveau cérébral et hépatique des ratons. Ce modèle expérimental nous permettra d'étudier ultérieurement les voies de signalisation qui régissent les interactions entre fer, stress oxydant et diabète gestationnel et d'évaluer les répercussions d'une augmentation des dommages oxydatifs chez les fœtus, chez les nouveau-nés à la naissance et à distance par des études de comportement. Enfin en raison des données récentes sur l'épigénétique notre modèle expérimental pourrait nous permettre de suivre l'évolution en terme d'apparition de pathologies à l'âge adulte (insulinorésistance, diabète de type 2, déclin cognitif) des animaux nés de mère avec un diabète gestationnel. Au vu de l`ensemble de nos résultats sur les interactions entre ferritine, intolérance au glucose et stress oxydant, le bénéfice d`une supplémentation martiale durant la grossesse chez des femmes à risque de diabète gestationnel doit être évalué. / The overall goal of this study was to establish the role of ferritin as a predictor for gestational diabetes mellitus and oxidative stress in non-anemic and non-iron supplemented Lebanese women. We observed that high ferritin level during the first-trimester of pregnancy was a predictor for impaired glucose tolerance, whereas high hemoglobin values yielded no significant relationship, suggesting that the iron reserve was the main indicator to be considered as a risk factor rather than the functional iron. Thus, the serum ferritin level could be used as a biological marker to assess for the risk of glucose intolerance in pregnant women. Based on the new World Health Organization criteria for gestational diabetes mellitus diagnosis, it is predicted that gestational diabetes mellitus prevalence in our population could be increased by four-fold. Since gestational diabetes mellitus has deleterious effects on the perinatal and maternal health outcomes, the implementation of these new criteria will allow for better management of blood glucose in pregnant women at risk for developing gestational diabetes mellitus. Although the new criteria adopted lower cut-off blood glucose value, hyperglycemia is still a factor that highly associated with increase oxidative stress, ultimately leading to DNA damage. Previously, we have shown that high iron status was associated with elevated oxidative stress. Furthermore, we have established that high ferritin during early-term pregnancy affected the association between oxidative stress and insulin resistance with glucose intolerance. Due to the lack of good experimental model to study gestational diabetes mellitus, we have utilized fructose-supplemented diet fed pregnant dam as an experimental animal model for our gestational diabetes studies. Data obtained in a preliminary study indicated that, this experimental animal model had identical metabolic modifications found in women with gestational diabetes mellitus. Moreover, we have showed that iron-enriched diet significantly increased the redox status of the brain and the liver of the fructose-supplemented dams. Therefore, we believed that this experimental model is good model for future studies to evaluate the signaling pathways involved in iron, oxidative stress and gestational diabetes and to assess the impact of increased oxidative damage during pregnancy on the fetus, immediately after birth and later during the developmental stages via various behavioral tests. Finally, an epigenetic study using this experimental model may allow us to understand the genetic alterations that affected the likelihood of developing insulin resistance, diabetes, or cognitive decline in pups born to the mothers with gestational diabetes. Based on the findings from our studies on the interaction between ferritin, glucose impairment, and oxidative stress, as well as the iron-supplemented diet in the dams with gestational diabetes mellitus, a caution must be exercised when supplementing a pregnant woman with iron. The use of iron-supplementation during pregnancy should be re-evaluated.

VIEIRA NETA, Francisca Adriele. Políticas públicas na saúde voltadas para o Diabetes Mellitus Gestacional: avaliação da aplicação no ciclo gravídico-puérperal. 2013. 88f. – Dissertação (Mestrado) – Universidade Federal do Ceará, Programa de Pós-graduação em Políticas Públicas e Gestão da Educação Superior, Fortaleza (CE), 2013. / Submitted by Márcia Araújo (marcia_m_bezerra@yahoo.com.br) on 2014-05-07T12:46:01Z No. of bitstreams: 1 2013_dis_favneta.pdf: 1117955 bytes, checksum: 50efe4a2d80c04a1a622b763935bbad2 (MD5) / Approved for entry into archive by Márcia Araújo(marcia_m_bezerra@yahoo.com.br) on 2014-05-08T14:37:26Z (GMT) No. of bitstreams: 1 2013_dis_favneta.pdf: 1117955 bytes, checksum: 50efe4a2d80c04a1a622b763935bbad2 (MD5) / Made available in DSpace on 2014-05-08T14:37:26Z (GMT). No. of bitstreams: 1 2013_dis_favneta.pdf: 1117955 bytes, checksum: 50efe4a2d80c04a1a622b763935bbad2 (MD5) Previous issue date: 2013 / The objective of this research was analyze the application of the public policies guidelines to the pregnant and postpartum with Gentional Diabetes Millitus during prenatal care, approaching the prevention, diagnosis and treatment. For this purpose, it was used a sample of 28 women with GDM at public and reference disease institute. An exploratory, descriptive and documentary survey was conducted approaching the quantitative. The instrument was a form and the technique, the structured interview. The data collection occurred from November 2012 to January 2013. First of all, we conducted a collection in charts and in antenatal card of the survey participants. Later on, the pregnates and postpartum women with Gestational Diabetes Mellitus diagnosed passed through an interview. The result of the research showed the balance between countries on public policies to pregnant and postpartum women with GDM, Brazil has the highest number of actions directed to gestational diabetes, for instance: prenatal care access in the first trimester of pregnancy; number of consultations according to those recommended by public policies, about the interval among childbirths, the majority took four years to get pregnant again, in the blood pressure check part, the pregnant women adhered during antenatal consultations over six times and the orientations received after the gestational diabetes diagnosis, the diet was the first guidance received. Nevertheless, remains the convenience of expansion and the creation of new public policies on health, targeted to pregnant and postpartum women with gestational diabetes mellitus, since this disease is still based on the guidelines established for chronic diseases. The DMG grows rapidly in uncomfortable level, and actions are insufficient to meet the health needs of this group. / A pesquisa teve como objetivo analisar a aplicação das diretrizes das políticas públicas dirigidas às gestantes e puérperas portadoras de Diabetes Mellitus Gestacional, durante o pré natal, abordando a prevenção, o diagnóstico e o tratamento. Para tanto, utilizou-se uma amostra com 28 mulheres portadoras de DMG em instituição pública e de referência para a doença. Realizou-se uma pesquisa documental, exploratória e descritiva com abordagem quantitativa. O instrumento foi um formulário, e a técnica, a entrevista estruturada. A coleta de dados ocorreu no período de novembro de 2012 a janeiro de 2013. Primeiramente foi realizada uma coleta em prontuários e no cartão de pré-natal das participantes do estudo. No segundo momento foi aplicada uma entrevista às gestantes e puérperas, com diagnóstico de Diabetes Mellitus Gestacional. A pesquisa mostrou na comparação entre países sobre as políticas públicas dirigidas às gestantes e puérperas com DMG, o Brasil destacou-se com o maior número de ações direcionado para o diabetes gestacional, e, mediante o resultado da pesquisa tivemos os seguintes resultados: acesso ao pré-natal no primeiro trimestre da gestação; número de consultas condizente com as preconizadas pelas políticas públicas; em referência ao intervalo entre partos a maioria levou mais de quatro anos para engravidar novamente; na categoria verificação da pressão arterial, as gestantes aferiram-na durante as consultas de pré-natais mais de seis vezes e quanto às orientações recebidas após a definição do diagnóstico de diabetes gestacional, a dieta foi a primeira orientação recebida. Mesmo assim, pontua-se a conveniência de ampliação e a criação de novas políticas públicas na saúde, direcionadas às gestantes e puérperas portadoras de diabetes mellitus gestacional, uma vez que, essa patologia ainda se baseia nas normas e diretrizes estabelecidas para as doenças crônicas. O DMG cresce rapidamente em patamar pouco confortável, e as ações são insuficientes para suprir as necessidades de saúde desse grupo.