A hipótese do presente estudo sugere que a baixa fertilidade de vacas Holandesas (Bos taurus) repetidoras de serviço (RS) está relacionada à baixa qualidade oocitária que, por sua vez, é associada ao quadro de resistência periférica a insulina (RPI). Ainda, a indução de lactação (IL) em vacas Holandesas (Bos taurus) RS pode reverter o quadro de RPI e, consequentemente, melhorar a qualidade oocitária e a produção in vitro de embriões (PIVE). Para testar a hipótese proposta, este estudo objetivou avaliar o efeito da fase da lactação e da gestação [Exp. 1], o efeito da secagem de RS [Exp. 2] e o efeito da IL [Exp. 3] sobre a RPI, a qualidade oocitária e a PIVE em vacas da raça Holandesa (Bos taurus). Nos três estudos foram realizados testes de tolerância à glicose (TTG) para avaliar a RPI através do perfil hormonal sérico de insulina e glicose. Além disso, avaliou-se o perfil bioquímico sérico e folicular e a qualidade oocitária através da PIVE. Verificou-se que, em resposta à infusão de 0,3mg glicose/kg PV, as vacas RS no final da lactação secretaram 53% mais insulina e captaram 40% menos de glicose quando comparadas as vacas no terço inicial de lactação (Exp 1). Esses achados são indicativos do estabelecimento do quadro de RPI nas vacas RS em lactação. Durante o período seco, as vacas RS secretaram 96% mais insulina e captaram 56% menos glicose que as vacas no terço inicial da lactação e as vacas RS em lactação, respectivamente (Exp. 2). Ainda, as vacas com lactação induzida secretaram 11% menos insulina e captaram a mesma quantidade de glicose que vacas paridas em fases semelhantes de lactação (Exp 3), demonstrando que o protocolo de IL foi eficiente em alterar o perfil metabólico, revertendo o quadro de RPI presente nas vacas RS. Nos Exp. 1, 2 e 3 foram verificadas maiores concentrações plasmática de triglicérides (TG; P &lt; 0,05), colesterol total (COL; P < 0,05) e LDL (P < 0,05) no soro sanguíneo em vacas RS quando comparadas com vacas no terço inicial de lactação. Durante o período seco (Exp. 2 e 3), observou-se incremento desses metabólitos, destacando aumento na concentração de TG (P < 0,05), COL (P < 0,05) e LDL (P < 0,05) plasmático em vacas secas quando comparadas as vacas em lactação [início e final (RS) da lactação]. No liquido folicular foram observadas variações no perfil bioquímico para COL e TG. Nos Exp. 1, 2 e 3, verificou-se que vacas RS possuem maior concentração de TG (P < 0,05) e COL (P < 0,05) no fluido folicular do que vacas no terço inicial de lactação. Contrariando a hipótese inicialmente proposta, as vacas RS em lactação e as vacas secas apresentaram maior taxa de blastocisto (P < 0,05) e número de blastocistos por OPU (P < 0,05) que as vacas no terço inicial de lactação (Exp. 1, 2 e 3). Através do perfil de insulina circulante em resposta ao TTG foi possível demonstrar o estabelecimento do quadro de RPI em vacas RS (P < 0,05). Além disso, constatou-se agravamento da RPI em vacas secas (P < 0,05). Esse quadro foi associado ao aumento do escore de condição corporal (P < 0,05) e do peso vivo (kg; P < 0,05) nas vacas RS. Em conclusão, não foi verificada associação negativa entre RPI, qualidade oocitária e PIVE em vacas Holandesas (Bos taurus) RS. Apesar da indução de lactação em vacas Holandesas (Bos taurus) RS alterar o metabolismo e diminuir o quadro de RPI, não foi verificado efetivo positivo na qualidade oocitária e na PIVE. / The hypothesis of the present study suggests that low fertility of repeat breeders (RB) Holstein (Bos taurus) cows is related to low oocyte quality, which is associated with peripheral insulin resistance (PIR). Also, induction of lactation (IL) in RB Holstein (Bos taurus) cows can revert PIR and, consequently, improve oocyte quality and in vitro embryo production (IVEP). In order to test the proposed hypothesis, the objective of this study was to evaluate the effect of phase of lactation and gestation [Exp. 1], effect of drying RB [Exp. 2] and effect of IL [Exp. 3] on PIR, oocyte quality and IVEP of Holstein (Bos taurus) cows. In all three studies, glucose tolerance tests (GTT) were performed to evaluate PIR through the serum hormonal insulin and glucose profile. In addition, we evaluated the serum and follicular biochemical profile and oocyte quality through IVEP. It was verified that, in response to a 0.3mg glucose/kg of body weight (BW), RB cows at the end of lactation secreted 53% more insulin and captured 40% less glucose when compared to cows in the initial third of their lactation (Exp. 1). These findings are indicative of the establishment of PIR in RB lactating cows. During the dry period, RB cows secreted 96% more insulin and captured 56% less glucose than cows in the initial third of their lactation and RB lactating cows, respectively (Exp. 2). Also, cows with induced lactation secreted 11% less insulin and captured the same amount of glucose than calved cows in similar lactation phase (Exp. 3), demonstrating that the IL protocol was efficient to alter the metabolic profile, reverting PIR present in RB cows. In Exp. 1, 2 and 3 higher plasmatic concentrations of triglycerides (TG; P<0.05), total cholesterol (COL; P<0.05) and LDL (P<0.05) were verified in the blood serum in RB cows when compared to cows in the initial third of their lactation. During the dry period (Exp. 2 and 3), we observed the increment of these metabolites, and a notable elevation of the plasmatic TG (P < 0.05), COL (P < 0.05) and LDL (P < 0.05) in dry cows when compared to lactating cows [beginning and end (RB) of lactation]. In the follicular fluid, it was possible to observe variations in the biochemical profile for COL and TG. In Exp. 1, 2 and 3, it was verified that RB cows have higher concentration of TG (P < 0.05) and COL (P < 0.05) in the follicular fluid than cows in the initial third of their lactation. Contrary to the initially proposed hypothesis, RB lactating cows and dry cows presented higher blastocyst rate (P<0.05) than cows in the initial third of lactation (Exp. 1, 2 and 3). Through the circulating insulin profile in response to the GTT it was possible to demonstrate the establishment of PIR in RB cows (P<0.05). Also, it was observed worsening of the PIR in dry cows (P<0.05). This condition was associated with an increase in body condition score (P<0.05) and BW (kg; P<0.05) in RB cows. In conclusion, no negative association between PIR, oocyte quality and IVEP was observed in RB Holstein (Bos taurus) cows. Although induction of lactation in RB Holstein (Bos taurus) cows altered the metabolism and reduced PIR, no positive effect was observed in oocyte quality and IVEP.

Trinta ovelhas, mestiças (Santa Inês X Dorper), adultas e hígidas foram selecionadas para avaliar o efeito da suplementação intramuscular com as vitaminas D e E no perfil bioquímico, metabolismo energético, metabolismo oxidativo, sensibilidade insulínica e imunidade no periparto. Após confirmação da gestação essas fêmeas foram distribuídas em três grupos de dez animais e no 108&deg; dia de gestação receberam veículo oleoso (grupo controle-GC); ou 70.000 UI/kg de P.V. de vitamina D3 (colecalciferol) (grupo tratado-GD); ou 60UI/kg de P.V. de vitamina E (-tocoferol) (grupo tratado-GE). As amostras de sangue foram coletadas previamente à aplicação da vitamina (-45), quatro (-30); e duas semanas (-15) antes do parto; até duas horas do parto (0), uma (7); duas (15); e quatro semanas após o parto (30). Foram analisadas as concentrações plasmáticas de glicose, beta hidroxibutirato (BHB), ácidos graxos não esterificados (AGNEs) e as concentrações séricas de colesterol, triglicérides, ureia, creatinina, cálcio total, cálcio iônico, proteína total, ácido úrico, aspartato amino transferase (AST), gamaglutamil transferase (GGT), e ainda a creatina quinase (CK). Foram também analisadas as concentrações de insulina e cortisol. Do metabolismo oxidativo foram determinadas as atividades da superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px), a habilidade de redução férrica plasmática (HRFP), substâncias reativas ao ácido tiobarbitúrico (TBARS), bem como o status antioxidante total (TAS). Para avaliar aspectos relacionados à imunidade de monócitos e neutrófilos, por método in vitro, em 24 ovelhas (seis de cada tratamento). As amostras de sangue foram coletadas nos momentos 30; 0; e 30 e avaliadas sem estímulo (burst basal) e com estímulo por DCFH-DA, SaPI e PMA. A imunofenotipagem com anticorpos monoclonais CD8, CD4, CD14, CD16, CD45R, WC1, CD206, foi realizada aos dias -30, -15,0,7 e 30. Foram determinadas as concentrações das vitaminas D e E, nos momentos pré-determinados das coletas e no dia do teste de tolerância à glicose (TTG), realizado para avaliar a sensibilidade insulínica, e foi calculado RQUICKI e RQUICKI BHB. Todas as variáveis estudadas apresentaram efeito de tempo. Houve interação tempo*tratamento em TBARS (P=0,0217) e tendência para vitamina E (0,0811), SOD (0,0886) e GSH-Px (P=0,0643). Houve efeito de tratamento no colesterol (P=0,0088) e vitamina D (P<0,0001) e tendência para TAS (P=0,0830). No TTG, com resultados de AUC de BHB e AGNE apresentaram efeito de número de fetos gestados (P=0,0006 e 0,0005 respectivamente) e o RQUICKIBHB mostrou-se melhor indicador de sensibilidade insulínica do que o RQUICKI em ovelhas. A suplementação com vitamina D influenciou os teores plasmáticos de alfa tocoferol e a resposta imune das ovelhas. A suplementação com vitamina E reduziu a peroxidação lipídica no parto e relacionou-se positivamente com a melhora oxidativa dos monócitos sem estímulo e estimulados por PMA. / Thirty healthy adult ewes were selected to evaluate the effect of supplementation with intramuscular vitamins D and E in peripartum period on the biochemical profile, energetic metabolism, oxidative metabolism, insulin sensitivity and immunity. After pregnancy confirmation these females were distributed into three groups of ten animals treated with intramuscular injection containing oily vehicle (control-to-control group) on the 108th day of pregnancy, (CG); or 70,000 IU / kg of body weight of vitamin D3 (cholecalciferol) (treated group-GD); or 60 IU / kg of body weight of vitamin E (-tocopherol) (treated group-GE). Blood samples were collected before the application of the vitamins and vehicle (-45), four (-30); and two weeks (-15) before lambing; until 2 hours of lambing (0); one (7), two (15) and four weeks postpartum (30). Plasma concentrations of glucose, beta hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum concentrations of cholesterol, triglycerides, urea, creatinine, total calcium, ionic calcium, total protein, uric acid, aspartate amino transferase (AST), gammaglutamyl transferase (GGT), and creatine kinase (CK) were measured. The concentrations of insulin and cortisol, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), plasma ferric reduction ability (FRAP), thiobarbituric acid reactive substances (TBARS), as well as total antioxidant status (TAS) were determinate. Monocytes and neutrophils were assessed by in vitro method to identify aspects related to immunity in 24 ewes (six from each treatment) at -30, 0 and 30. Blood samples were evaluated without stimulus (basal burst), with DCFH-DA, SaPI and PMA stimulus. Immunophenotyping with monoclonal antibodies CD8, CD4, CD14, CD16, CD45R, WC1, CD206 were performed at -30, -15, 0, 7 and 30. The concentrations of vitamins D and E were determinate at the predetermined collection times and on the day of the Intravenous Glucose Tolerance Test (IVGTT), realized to evaluate the insulin sensitivity, as well as RQUICKI and RQUICKI BHB. All variables studied showed time effects. There were interaction time * treatment in TBARS (P = 0.0217) and tendency for vitamin E (0.0811), SOD (0.0886) and GSH-Px 16 (P = 0.0643). Treatment effect on cholesterol (P = 0.0088) and vitamin D (P &lt;0.0001) and tendency for TAS (P = 0.0830) were observed. About of IVGTT, AUC results of BHB and AGNE showed number of fetuses effect (P = 0.0006 and 0.0005 respectively). RQUICKIBHB was a better indicator of insulin sensitivity than RQUICKI in ewes. Vitamin D supplementation influenced the plasma levels of alpha tocopherol and the immune response of ewes. Vitamin E supplementation reduced lipid peroxidation at parturition and was positively related to the oxidative improvement of the monocytes without stimulation and stimulated by PMA. High doses of vitamins D or E administered 45 days before parturition on healthy ewes can be beneficial; however more studies are needed about this topic.

INTRODUCTION/OBJECTIVES: Current screening guidelines for pre-diabetes and type 2 diabetes mellitus note that there are discrepancies in diagnosing the disease using the fasting plasma glucose test, oral glucose tolerance test, and HbA1c in high-risk populations. The objective of this study is to compare the effectiveness of screening methods for type 2 diabetes mellitus (T2DM) and pre-diabetes by race/ethnicity and gender. METHODS: Secondary analyses of the National Health and Nutrition Examination Survey (NHANES, 2005-2008) were performed using SPSS 19.0. Screening outcomes were assessed and compared for a sample of n=10,566, NHW, NHB, MA, and Multiracial/other men and women. Analyses included cross tabulations, ANOVA and partial correlations to establish disease prevalence, effectiveness of screenings, and statistical significance. RESULTS: It was found that the HbA1c test is comparable in precision, and is correlated with the FPG for racial and ethnic minorities. The specificities for detecting pre-diabetes using the HbA1c were higher (64-66%) for these groups than by using the standard, FPG screening method (42-49%). There were no strong, significant differences for screening effectiveness for men versus women. DISCUSSION: This study revealed that the HbA1c test might be an effective method for screening for pre-diabetes in racial and ethnic minorities instead of the FPG test alone. Screening in high-risk populations will help delay the onset of T2DM, with increased prevention during the pre-clinical phase.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Trinta ovelhas, mestiças (Santa Inês X Dorper), adultas e hígidas foram selecionadas para avaliar o efeito da suplementação intramuscular com as vitaminas D e E no perfil bioquímico, metabolismo energético, metabolismo oxidativo, sensibilidade insulínica e imunidade no periparto. Após confirmação da gestação essas fêmeas foram distribuídas em três grupos de dez animais e no 108&deg; dia de gestação receberam veículo oleoso (grupo controle-GC); ou 70.000 UI/kg de P.V. de vitamina D3 (colecalciferol) (grupo tratado-GD); ou 60UI/kg de P.V. de vitamina E (-tocoferol) (grupo tratado-GE). As amostras de sangue foram coletadas previamente à aplicação da vitamina (-45), quatro (-30); e duas semanas (-15) antes do parto; até duas horas do parto (0), uma (7); duas (15); e quatro semanas após o parto (30). Foram analisadas as concentrações plasmáticas de glicose, beta hidroxibutirato (BHB), ácidos graxos não esterificados (AGNEs) e as concentrações séricas de colesterol, triglicérides, ureia, creatinina, cálcio total, cálcio iônico, proteína total, ácido úrico, aspartato amino transferase (AST), gamaglutamil transferase (GGT), e ainda a creatina quinase (CK). Foram também analisadas as concentrações de insulina e cortisol. Do metabolismo oxidativo foram determinadas as atividades da superóxido dismutase (SOD) e glutationa peroxidase (GSH-Px), a habilidade de redução férrica plasmática (HRFP), substâncias reativas ao ácido tiobarbitúrico (TBARS), bem como o status antioxidante total (TAS). Para avaliar aspectos relacionados à imunidade de monócitos e neutrófilos, por método in vitro, em 24 ovelhas (seis de cada tratamento). As amostras de sangue foram coletadas nos momentos 30; 0; e 30 e avaliadas sem estímulo (burst basal) e com estímulo por DCFH-DA, SaPI e PMA. A imunofenotipagem com anticorpos monoclonais CD8, CD4, CD14, CD16, CD45R, WC1, CD206, foi realizada aos dias -30, -15,0,7 e 30. Foram determinadas as concentrações das vitaminas D e E, nos momentos pré-determinados das coletas e no dia do teste de tolerância à glicose (TTG), realizado para avaliar a sensibilidade insulínica, e foi calculado RQUICKI e RQUICKI BHB. Todas as variáveis estudadas apresentaram efeito de tempo. Houve interação tempo*tratamento em TBARS (P=0,0217) e tendência para vitamina E (0,0811), SOD (0,0886) e GSH-Px (P=0,0643). Houve efeito de tratamento no colesterol (P=0,0088) e vitamina D (P<0,0001) e tendência para TAS (P=0,0830). No TTG, com resultados de AUC de BHB e AGNE apresentaram efeito de número de fetos gestados (P=0,0006 e 0,0005 respectivamente) e o RQUICKIBHB mostrou-se melhor indicador de sensibilidade insulínica do que o RQUICKI em ovelhas. A suplementação com vitamina D influenciou os teores plasmáticos de alfa tocoferol e a resposta imune das ovelhas. A suplementação com vitamina E reduziu a peroxidação lipídica no parto e relacionou-se positivamente com a melhora oxidativa dos monócitos sem estímulo e estimulados por PMA. / Thirty healthy adult ewes were selected to evaluate the effect of supplementation with intramuscular vitamins D and E in peripartum period on the biochemical profile, energetic metabolism, oxidative metabolism, insulin sensitivity and immunity. After pregnancy confirmation these females were distributed into three groups of ten animals treated with intramuscular injection containing oily vehicle (control-to-control group) on the 108th day of pregnancy, (CG); or 70,000 IU / kg of body weight of vitamin D3 (cholecalciferol) (treated group-GD); or 60 IU / kg of body weight of vitamin E (-tocopherol) (treated group-GE). Blood samples were collected before the application of the vitamins and vehicle (-45), four (-30); and two weeks (-15) before lambing; until 2 hours of lambing (0); one (7), two (15) and four weeks postpartum (30). Plasma concentrations of glucose, beta hydroxybutyrate (BHB), non-esterified fatty acids (NEFA) and serum concentrations of cholesterol, triglycerides, urea, creatinine, total calcium, ionic calcium, total protein, uric acid, aspartate amino transferase (AST), gammaglutamyl transferase (GGT), and creatine kinase (CK) were measured. The concentrations of insulin and cortisol, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), plasma ferric reduction ability (FRAP), thiobarbituric acid reactive substances (TBARS), as well as total antioxidant status (TAS) were determinate. Monocytes and neutrophils were assessed by in vitro method to identify aspects related to immunity in 24 ewes (six from each treatment) at -30, 0 and 30. Blood samples were evaluated without stimulus (basal burst), with DCFH-DA, SaPI and PMA stimulus. Immunophenotyping with monoclonal antibodies CD8, CD4, CD14, CD16, CD45R, WC1, CD206 were performed at -30, -15, 0, 7 and 30. The concentrations of vitamins D and E were determinate at the predetermined collection times and on the day of the Intravenous Glucose Tolerance Test (IVGTT), realized to evaluate the insulin sensitivity, as well as RQUICKI and RQUICKI BHB. All variables studied showed time effects. There were interaction time * treatment in TBARS (P = 0.0217) and tendency for vitamin E (0.0811), SOD (0.0886) and GSH-Px 16 (P = 0.0643). Treatment effect on cholesterol (P = 0.0088) and vitamin D (P &lt;0.0001) and tendency for TAS (P = 0.0830) were observed. About of IVGTT, AUC results of BHB and AGNE showed number of fetuses effect (P = 0.0006 and 0.0005 respectively). RQUICKIBHB was a better indicator of insulin sensitivity than RQUICKI in ewes. Vitamin D supplementation influenced the plasma levels of alpha tocopherol and the immune response of ewes. Vitamin E supplementation reduced lipid peroxidation at parturition and was positively related to the oxidative improvement of the monocytes without stimulation and stimulated by PMA. High doses of vitamins D or E administered 45 days before parturition on healthy ewes can be beneficial; however more studies are needed about this topic.

Abstract Gestational diabetes (GDM) indicates increased risk for diabetes and the metabolic syndrome in women. Research on prenatal exposure to GDM as a risk factor for metabolic diseases is conflicting. Overweight (body mass index ≥ 25 kg/m2) is a strong risk factor for GDM and metabolic diseases; however, there are few published previous studies distinguishing the separate effects of overweight and GDM on the later risk for metabolic diseases in women and their children. The present study evaluated pre-pregnancy overweight and GDM as determinants of long-term risk for diabetes and hypertension in women, and the metabolic consequences of prenatal exposures to maternal pre-pregnancy overweight and different types of maternal diabetes in children. The results are based on prospective, clinical data from Oulu University Hospital (n = 63 mothers and their children), and the Northern Finland Birth Cohort 1986 (NFBC 1986, n = 9,362 mothers and their 9,479 children). Compared to normal-weight mothers with normal glucose tolerance in pregnancy, the NFBC 1986 mothers with simultaneous pre-pregnancy overweight and GDM had strikingly high risks for developing diabetes (hazard ratio, HR 47.2; 95% confidence interval 25.5–87.4) and hypertension (HR 9.2 [6.1–13.9]) twenty years after delivery. The risks for these diseases were elevated in mothers with pre-pregnancy overweight even when they had normal glucose tolerance during pregnancy (HR diabetes 12.6 [7.4–21.6], HR hypertension 2.9 [2.1–3.9]). GDM per se indicated increased risk only for diabetes (HR 10.6 [4.2–27.0]). In the cohort from Oulu University Hospital, increased fasting insulin concentration (P = 0.04), first phase insulin response (P = 0.03), and HOMA-B (P = 0.008) were already observed at pre-school age in the offspring of mothers with Type 1 diabetes compared with offspring of mothers with GDM. In the NFBC 1986 offspring, the prevalence of metabolic syndrome was 2.4% at age 16 years, using the International Diabetes Federation pediatric definition. Abdominal obesity, a waist girth over half one’s length, defined approximately 85% of the adolescents with metabolic syndrome. The risks for overweight and abdominal obesity were high in those with prenatal exposure to both maternal pre-pregnancy overweight and GDM (odds ratio for overweight 4.1 [1.9–8.6], for abdominal obesity 3.8 [1.7–8.8]). In children of normal-weight women, prenatal exposure to GDM was not associated with increased risk of these outcomes. Based on this study, preventing and reducing overweight in fertile age seems to be a key target for preventing metabolic diseases in women and their children.

Abstract Type 2 diabetes can be prevented if the impaired glucose tolerance is found. Oral glucose tolerance test is needed in clinical practise for that but it is expensive and inconvenient. Obesity, hypertension, dyslipidemia and hypertension in pregnancy are factors often found in persons with type 2 diabetes. When there are more than one factor in same person the risk of type 2 diabetes multiplies. The purpose of this study was to investigate the prevalence of abnormal glucose metabolism and risk factors of type 2 diabetes in middle aged Finnish population in Savitaipale municipality and develop a method to screen abnormal glucose metabolism in primary health care. It was also studied the correlation of blood pressure and body mass index during pregnancy and abnormal glucose metabolism in later life. The study population was 1561 people born 1933–1956. 77,5% participated and 1097 people of them not having known abnormal glucose metabolism were taken to the cross-sectional study to develop the screening method. All 325 women who have had childbirth and files of that were taken to the prospective pregnancy cohort study. Information was collected with interview, measurements, laboratory research and from childbirth files. According the World Health Organisation criteria 1999 the prevalence of diabetes was 8,7% in men and 7,4% in women, previously undiagnosed 3,9% and 3,1%. Every fourth had abnormal glucose metabolism (men 23,2%, women 23,5%). The prevalence of obesity, hypertension, use of long-term antihypertensive medication and dyslipidemia (only in women) was higher among those, who had abnormal glucose metabolism. Logistic models were made for the classified risk factors. The model (AUC 0.718 for men, 0.761 for women) containing age, gender, waist circumference, systolic blood pressure and use of long-term antihypertensive medication was as good as model containing in addition family history of diabetes, smoking habits, serum lipids and long-term use of lipid lowering medication. Risk score tables were made from classified risk factors to evaluate the probability of the abnormal glucose metabolism. The blood pressure level and body mass index in pregnancy correlated independently with abnormal glucose metabolism in later life, blood pressure also adjusted with body mass index. Hypertension in pregnancy or after delivery correlated with abnormal glucose metabolism adjusted with body mass index. Hypertension in pregnancy doubled the risk of abnormal glucose metabolism in later life adjusted for body mass index in pregnancy and hypertension in later life. This information is important in prevention of type 2 diabetes. / Tiivistelmä Tyypin 2 diabetesta voidaan estää, mikäli heikentynyt glukoosinsieto tunnistetaan. Siihen tarvitaan glukoosirasituskoetta, jota on pidetty kalliina ja hankalana toteuttaa. Lihavuus, kohonnut verenpaine, dyslipidemia ja raskausdiabetes ovat tyypin 2 diabeteksen riskitekijöitä ja niiden ryvästyminen samaan henkilöön lisää diabetekseen sairastumisen todennäköisyyttä. Tyypin 2 diabeteksen riskitekijöiden ja poikkeavan glukoosiaineenvaihdunnan määrää ja raskauden aikaisen verenpaineen yhteyttä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan tutkittiin 1933–1956 syntyneessä savitaipalelaisessa väestössä. Tavoitteena oli kehittää perusterveydenhuoltoon soveltuva poikkeavan glukoosiaineenvaihdunnan seulontamenetelmä. Kohdejoukosta (n = 1561) osallistui 77,5 %, joista 1097:llä henkilöllä ei tiedetty olevan diabetesta. Heistä kerättiin tietoa haastattelulla, mittauksilla ja laboratoriotutkimuksilla sekä äitiysneuvolakorteista. Raskausaineistoon ja takenevaan kohorttitutkimukseen otettiin kaikki ne 325 naista, myös diabeetikot, joista raskaudesta oli tiedot käytettävissä. Diabetesta sairasti 8,7 % miehistä ja 7,4 % naisista, aiemmin diagnosoimattomia oli 3,9 % ja 3,1 %. Poikkeava glukoosiaineenvaihdunta oli joka neljännellä. Lihavuutta, kohonnutta verenpainetta, verenpainelääkkeen käyttöä ja naisilla dyslipidemiaa oli enemmän niillä, joilla oli poikkeava glukoosiaineenvaihdunta. Tutkimuksessa luotiin luokitelluista muuttujista logistisia malleja. Malli, johon muuttujiksi valittiin ikä, sukupuoli, vyötärön ympärys, systolinen verenpaine ja verenpainelääkkeen käyttö, todettiin yhtä hyväksi (miesten ROC -käyrän AUC 0.718, naisten 0.761) ennustamaan heikentynyt glukoosinsieto ja diabetes kuin malli, johon lisäksi valittiin suvun diabetes, tupakointi, rasva-arvoja ja lipidilääkityksen käyttö. Muuttujista tehtiin taulut, joista voi nähdä poikkeavan glukoosiaineenvaihdunnan todennäköisyyden. Raskauden aikainen verenpaine ja painoindeksi olivat yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan, samoin loppuraskauden verenpaine painoindeksillä vakioituna. Raskaudessa todettu kohonnut verenpaine oli, mutta raskauden aiheuttama kohonnut verenpaine ei ollut, yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan painoindeksistä riippumatta, samoin loppuraskauden diastolinen verenpaine seulonnan diastolisesta verenpaineesta riippumatta. Raskaudessa tai sen jälkeen todettu kohonnut verenpaine kaksinkertaisti poikkeavan glukoosiaineenvaihdunnan riskin loppuraskauden painoindeksistä tai seulonnassa todetusta kohonneesta verenpaineesta riippumatta. Kahdella helposti mitattavalla muuttujalla voidaan päätellä glukoosirasituskokeen tarve. Diabetesta ehkäistäessä on tärkeä tietää, että raskauden kohonnut verenpaine ja ylipaino lisäävät myöhempää poikkeavaa glukoosiaineenvaihduntaa.

Objetivo: Determinar potenciales factores de riesgo para diabetes mellitus gestacional (DMG). Métodos: Estudio de casos y controles realizado en el Hospital Alberto Sabogal mediante recolección de historias clínicas del 2009 a 2014. Se define como caso las gestantes con diagnóstico de DMG mediante una prueba de tolerancia oral a la glucosa (PTOG), previa glucosa en ayunas anormal y control a la gestante sin valores indicativos de DMG. Las variables de interés fueron paridad, antecedente de cesáreas, abortos y recién nacido con mayor peso. Modelos de regresión logística fueron calculados para estimar odd ratios (OR) e intervalos de confianza al 95% (IC95%). Resultados: Se incluyeron 84 casos y 336 controles. En el modelo multivariado, la multiparidad incrementó el riesgo de DMG (OR= 3,54; IC95% 1,55 – 8,14). También, antecedente de abortos, a partir del segundo aborto (OR= 3,40, IC95% 1,55 – 7,44) y cesáreas previas (1 cesárea OR= 3,5 IC95% 1,89 – 6,47 y 2+ cesáreas OR=8,35 IC95% 3,50 – 19,95). La multiparidad, dos o más abortos y mayor número de cesáreas son factores de riesgo para DMG. / Objectives: To identify risk factors for gestational diabetes mellitus (GDM). Methods: A case-control study was performed in Alberto Sabogal Hospital, collecting medical records from 2009 to 2014. A case was defined as a pregnant women diagnosed with GDM by an oral glucose tolerance test (OGTT) after an abnormal fasting glucose and control was defined as a pregnant women without GDM indicative values. The study outcome was GDM. The variables of interest were multiparity, previous cesarean section, abortions, newborn with the greatest weight. Logistic regression were used to calculate the odds ratio (OR) and a confidence interval of 95% (IC95%). Results: 84 cases and 336 controls were included. In the multivariate model, multiparity increased risk of GDM (OR= 3.54, 95% CI 1.55 to 8.14). As well history of abortions, from the second abortion (OR= 3.40, 95% CI 1.55 to 7.44) and previous cesarean section are also related (cesarean section 1 OR= 3.5 95% CI 1.89 to 6.47 and 2+ cesarean OR= 8.35 95% CI 3.50 to 19.95). Multiparity, two or more abortions, a biggest number of cesarean sections are GDM risk factors.

Abstract Background: The objective of the study was to investigate the association of neck circumference (NC) to parameters of glucose homeostasis compared to classical anthropo- metric parameters of lean and obese children. Methods: Three dimensional (3D)-body scanning quan- tified anthropometric (height, weight, NC, hip/waist circumference, BMI) and metabolic parameters (fasting plasma glucose [FPG], insulin, HbA1c, oGTT, HOMA-IR) were determined cross-sectionally in 1542 participants (5–18 years). the strongest association to glucose metabolism para- meters was found for waist circumference (WC), except for FPG and 2h-postload glucose. In multiple linear regres- sion analyses, NC provided additional benefit beyond classical anthropometric indices to describe impairment of glucose homeostasis. Conclusions: We suggest that NC is comparable or addi- tive to established anthropometric parameters but might not be superior to them. However NC is simple to measure, reproducible and may be considered in clinical practice as an additional measurement tool.:Inhalt I Abkürzungsverzeichnis 1. Einführung in die Thematik 1.1. Einleitung und Definition 1.2. Zielsetzung der Arbeit 1.3. wissenschaftlicher Hintergrund 1.4. LIFE Child 2. Publikation Zusammenfassung der Arbeit Literaturverzeichnis Darstellung wissenschaftlicher Beitrag Erklärung über die eigenständige Abfassung der Arbeit Danksagung

Résumé : Le diabète gestationnel (DG), qui peut entraîner des conséquences importantes pour la mère et l’enfant, résulte d’un défaut de compensation de la sécrétion d’insuline par rapport à la résistance à l’insuline. Comme la grossesse représente en elle-même un modèle d’augmentation physiologique de la résistance à l’insuline, il est intéressant d’étudier et de caractériser les facteurs qui sont impliqués dans la résistance à l’insuline et, ultimement, dans le DG, chez la femme enceinte. Le Tumor necrosis factor alpha (TNFα) est soupçonné d’être un de ces facteurs, suite aux études effectuées chez les animaux et les populations humaines non enceintes, mais les résultats obtenus en grossesse sont encore controversés. Nous avons émis l’hypothèse que les niveaux circulants de TNFα sont associés au DG et à la résistance à l’insuline dans une large cohorte de femmes enceintes. Nous avons aussi investigué les variations des niveaux de TNFα en réponse à l’hyperglycémie provoquée par voie orale (HGPO) chez des femmes enceintes. Nous avons montré que de hauts niveaux de TNFα étaient liés à une résistance à l’insuline augmentée au 2e trimestre de la grossesse et ce, indépendamment de l’âge, de l’adiposité, de l’âge gestationnel, des triglycérides et des niveaux circulants d’adiponectine dans notre cohorte. De plus, les niveaux de TNFα varient différemment au cours de l’HGPO selon le statut de résistance à l’insuline. En effet, les niveaux de TNFα augmentent à 1h puis diminuent à 2h chez les femmes les plus sensibles à l’insuline, alors qu’ils diminuent tout au long du test chez les femmes les plus résistantes à l’insuline, mais restent en tout temps supérieurs aux niveaux mesurés chez les femmes les plus sensibles à l’insuline. Toutefois, les niveaux de TNFα n’étaient pas différents entre les femmes avec DG et celles normoglycémiques. De façon intéressante, la variation du TNFα pendant l’HGPO chez les femmes DG est similaire à celle chez les femmes avec haute résistance à l’insuline. Ces résultats suggèrent donc que le TNFα est indépendamment associé à la résistance à l’insuline en grossesse et que les voies inflammatoires peuvent contribuer aux dysfonctions glycémiques retrouvées en DG. // Abstract : Gestational diabetes mellitus (GDM), which can exert important impacts on mothers and offspring, results from an imbalance between insulin secretion capacity and insulin resistance. Pregnancy is a state of physiologically increased insulin resistance, providing a unique model to study and characterize biological factors linked to insulin resistance in humans and, ultimately, GDM, in pregnant women. Based on animal studies and analyses in non-pregnant populations, tumor necrosis factor alpha (TNFα) is suspected of being involved in insulin resistance, but results obtained from pregnant populations are still controversial. Our hypothesis was that circulating TNFα would be associated with GDM and insulin resistance in a large cohort of pregnant women. We also investigated dynamic variations of TNFα levels over the course of an oral glucose tolerance test (OGTT) in pregnant women. We showed that higher TNFα levels were associated with higher insulin resistance at 2nd trimester of pregnancy, independent of age, adiposity, gestational age, triglycerides and adiponectin levels in our cohort. Furthermore, TNFα levels varied differently over the course of the OGTT according to insulin resistance status: they rose at 1h and then decreased at 2h in insulin sensitive women, whereas they consistently decreased in insulin resistant women over the course of the test (even though they remained statistically higher than insulin sensitive women’s levels at each time point throughout the OGTT). However, TNFα levels were not different between GDM and non-GDM women. Interestingly, variation of TNFα levels over the course of the OGTT in GDM women followed the same pattern as the variation observed in OGTT in women classified with high insulin resistance. Those results suggest that circulating TNFα is independently associated with insulin resistance in pregnancy and that inflammatory pathways might contribute to glycemic dysregulation observed in GDM.