Clinical and metabolic characteristics of treated hyperlipidemic patients additionally affected by subclinical hyperglycemia

Background Impaired glucose regulation (IGR) and hyperlipidemia (HL) are associated with an increased risk of developing a cardiovascular disease. Hyperlipidemic patients were shown to bear a greater risk for an increased intima media thickness (IMT). However little is known about differences between treated hyperlipidemic patients (HL) with normal (NGR) or impaired (IGR) glucose regulation. Methods We performed a cross-sectional study, involving 96 non-diabetic HL patients with IGR (fasting plasma glucose of 100 mg/dl and <126 mg/dl or/and HbA1c-level of 5.7 and <6.5 %) or with NGR (HbA1c-level of <5.7 % and a fasting glucose <100 mg/dl). We compared metabolic characteristics and the IMT between the two groups. Insulin sensitivity in fasting conditions was described by HOMA-IR and QUICKI. Results HL-IGR patients were older (57.6 10.4 vs. 49.1 8.7, p < 0.001), had higher carotid IMT measurements (IMT average: 0.68 0.14 vs. 0.60 0.09, p = 0.002; IMT right: 0.67 0.15 vs. 0.60 0.10, p = 0.013; IMT left: 0.63 vs. 0.57, p = 0.009), as well as a higher chance to exceed a cut-off value of 0.8 mm or insignificant stenosis within this investigation (OR: 3.9, 95 % CI: 1.15-13.22, p = 0.029) compared to HL-NGR-patients. Furthermore HL-IGR patients were characterised by a higher waist circumference (100.6 10.1 vs. 91.6 13.3, p < 0.001), higher fasting plasma glucose-levels (100.1 10.8 vs. 88.1 6.6, p < 0.001), higher HbA1c concentrations (5.8 0.33 vs. 5.3 0.24, p < 0.001) and C-peptide levels (2.70 vs. 2.10, p = 0.012). Age and CVD status were in general the only two variables which independently explained IMT. Conclusion Our study showed that among patients with treated hyperlipidemia the presence of IGR characterised subjects who were older and had a significantly higher risk for an increased IMT compared with those maintaining NGR. Further studies are necessary to evaluate if this specific subpopulation with IGR can benefit from a more strict multifactorial management and perhaps from an additional early antihyperglycaemic treatment.(VLID)511297

Cardiometabolic Risk in Hyperlipidemic Men and Women

Objective. The aim of this study was to evaluate sex specific differences of metabolic and clinical characteristics of treated hyperlipidemic men and women (HL-men and HL-women). Methods. In this study vascular and metabolic characteristics of 35 HL-women and 64 HL-men were assessed. In addition a sex specific analysis of metabolic and nutritional habits of HL-patients with prediabetes (HL-IGR) was done. Results. HL-women were older and had favourable concentrations of high density lipoprotein cholesterol (HDL-cholesterol), triglycerides (TG), and triglyceride/HDL-cholesterol ratio (TG/HDL-ratio) but were also shown to have higher concentrations of lipoprotein-a compared to HL-men. HL-men were characterized as having higher levels of liver-specific parameters and body weight as well as being more physically active compared to HL-women. Brain natriuretic peptide (pro-BNP) was higher in HL-women than HL-men, while no differences in metabolic syndrome and glycemic parameters were shown. HL-IGR-women were also older and still had a better profile of sex specific lipid parameters, as well as a lower body weight compared to HL-IGR-men. No differences were seen in vascular parameters such as the intima media thickness (IMT). Conclusion. HL-women were older and had overall more favourable concentrations of lipid parameters and liver enzymes but did not differ regarding vascular morphology and insulin sensitivity compared to HL-men of comparable body mass index (BMI)

The impact of diabetes during pregnancy on metabolism of offspring and mothers from pregnancy to five to ten years after delivery

Gestationsdiabetes (GDM) stellt für betroffene Frauen und Kinder einen wichtigen prognostischen Marker für die spätere Entwicklung von Stoffwechselstörungen dar und gewinnt somit aufgrund der weltweit wachsenden Diabetes und Adipositas Prävalenz zunehmende Relevanz. Eine Evaluierung von Risikofaktoren, welche mit einer Manifestation von GDM und dessen Langzeitfolgen einhergehen, ist notwendig um effektive Präventionsmaßnahmen zu entwickeln. Das Ziel dieser Arbeit ist daher Risikofaktoren in Zusammenschau mit verschiedenen Aspekten von GDM zu evaluieren, welche einerseits langfristige Folgen für Mutter und Kind, sowie das schwangerschaftsbezogene Outcome beeinflussen könnten. Vier Studien wurden im Rahmen dieser Dissertation durchgeführt: Zunächst wurden Daten einer Kohorte von Frauen mit positiver GDM Anamnese, welche prospektiv über einen Zeitraum von 10 Jahren nachuntersucht wurden, auf Zusammenhänge zwischen Fettleber und Diabetesmanifestation analysiert. Daneben wurden Kinder von Müttern mit Diabetes im Alter von 5-10 Jahren metabolisch charakterisiert. Weiters wurden Schwangerschaften im Verlauf beobachtet um mögliche Assoziationen zwischen metabolischen Risikofaktoren und früher Glukosetoleranzstörung und Übergewicht sowie deren Folgen für das schwangerschaftsbezogene Outcome zu bewerten. Zusammenfassend eröffnen unsere Daten neue Einsichten in die möglichen Implikationen von GDM/Diabetes in der Schwangerschaft: Auch 10 Jahre nach GDM Manifestation zeigten sich Zusammenhänge zwischen Fettleber, Insulinresistenz, prothrombotischen/ proinflammatorischen Faktoren und einer späteren Typ 2 Diabetes Entwicklung. Bei Kindern aus diabetischen Schwangerschaften wurden frühe Anzeichen für Insulinresistenz in Abhängigkeit von BMI und Leptin festgestellt. Auch während der Schwangerschaft scheint Insulinresistenz für eine frühe GDM Manifestation entscheidend zu sein. Hierbei stellt das präkonzeptionelle Übergewicht einen bedeutenden Risikofaktor dar, da es des Weiteren auch mit charakteristischen Veränderungen im Lipidprofil einhergeht. Das klinische Management von GDM kann in Hinblick auf Kurz- und Langzeitfolgen für Mutter und Kind durch eine entsprechende Risikostratifizierung deutlich verbessert werden.The prognostic value of gestational diabetes (GDM) for further deterioration in insulin resistance (IR) and diabetes manifestation of affected women and their offspring is gaining growing interest due to the worldwide diabetes and obesity epidemic. In this respect identification of risk factors associated with manifestation of GDM as well as appropriate prediction of chance for long-term consequences would support efforts in improving future prevention measures. The objective of this thesis is to characterize associations of metabolic risk factors with various aspects of GDM related to future long-term consequences in affected women and offspring as well as to manifestation time, progress and outcome under special consideration of effects of obesity during pregnancy. Four studies were performed in the framework of this thesis: first actual data of a former cohort were assessed in order to evaluate metabolic conditions in women with previous GDM; for this purpose follow-up examinations of glucometabolic state 10 years after index pregnancy were performed and evaluated in relation to early postpartum data. In addition young offspring exposed to diabetes during pregnancy aged 5-10 years were prospectively examined for prevalence of obesity as well as of features of glucose metabolism indicative for early IR. Further, a prospective study was performed monitoring women during their pregnancy progress till delivery to investigate associations between metabolic risk factors for early dysglycemia and obesity during gestation and their consequences for pregnancy outcome. In summary this thesis gives additional insight in possible implications of GDM: metabolic determinants for fatty liver are strongly related to IR, also prothrombotic/proinflammatory factors and predicted women at risk for type 2 diabetes within 10 years after GDM. Early features of long-term consequences in offspring of diabetic pregnancies was also observable as IR in those who were exposed was significantly correlated to BMI or leptin levels already in young ages. During pregnancy time of GDM manifestation is associated with specific impairments in glucose disposal that are already detectable in early stage of pregnancy. Pregestational obesity is an important risk factor showing associations with diverging trajectories of lipids compared to normal-weight women. Management of GDM may be improved by appropriate risk stratification and special awareness on early features of deteriorated metabolism which impact pregnancy progress and outcome as well as metabolic long-term development of affected women and offspring.Zusammenfassung in deutscher SpracheAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersMedizinische Universität Wien, Dissertation, 2016OeBB(VLID)171588

Adiponectin and Leptin at Early Pregnancy: Association to Actual Glucose Disposal and Risk for GDM—A Prospective Cohort Study

Aim. There is scarce information on associations of adipokines, and concurrent glucose disposal during early pregnancy as performance of oral glucose tolerance is uncommon before 24th gestational week. We sought to examine associations of leptin and adiponectin to insulin sensitivity already at early pregnancy before recommended screening for GDM and to describe trajectories of adiponectin in relation to GDM status. Methods. 216 pregnant women were prospectively included at 16th (IQR: 14–18) gestational week (GW) for fasting adiponectin and leptin with subsequent OGTT testing for evaluation of insulin sensitivity and β-cell function. Follow-ups of adiponectin were performed at further four visits until 8–12 weeks after delivery. Results. In early pregnancy, differences in adiponectin and leptin were significant between GDM women (n=82) and controls (n=134), whereby those with early GDM (<21st week, n=49) showed more distinguishing levels (adiponectin: 8.5 ± 3.8 versus 10.4 ± 4.4 μg/ml, p=0.004; leptin 93.4 ± 38.5 versus 78.0 ± 39.2 μg/ml, p=0.005). Both adipokines were significantly associated with insulin sensitivity and β-cell function. Their attribution for GDM prediction was moderate to fair and more enhanced in early GDM. Trajectories of adiponectin remained constantly lower in GDM women, whereas dynamics in controls showed initially increased concentrations with decreasing tendency until 3rd trimester. After delivery, low adiponectin was associated with glucose dysregulation. Conclusion. Associations of adiponectin and leptin with features of deteriorated glucose metabolism at early gestation may be indicative for the endocrine involvement of adipose tissue in the manifestation of GDM and thus predictive for later impairments in metabolic flexibility in women at risk