ABSTRACT
OBJECTIVES: To compare: 1) 75 g oral glucose tolerance test (OGTT) and self-monitoring of blood glucose (SMBG) in identifying gestational diabetes mellitus (GDM) and other hyperglycemic statuses in pregnant women; 2) pregnancy outcomes according to glycemic status; and 3) participants' opinions regarding both methods. METHODS: A prospective study in women with a 50 g glucose load test ≥7.2 mmol/L at 24 to 28 weeks' gestation and singleton pregnancy. Women underwent OGTT (blinded) at day 1, followed by 7 days of SMBG (4 daily measurements: fasting and 2 h postprandially) without modifying diet or lifestyle. GDM (OGTT+) was diagnosed using the criteria of the International Association of the Diabetes and Pregnancy Study Groups, while pregnancy hyperglycemia (SMBG+) was defined as ≥4/7 glucose values ≥5.3 after fasting or ≥6.7 mmol/L 2 h postprandially for any meal of the day. Equivalent management was provided to women with GDM and/or pregnancy-related hyperglycemia. RESULTS: We divided 103 participants (age: 29.5±5.0 years; prepregnancy body mass index: 25.3±5.4 kg/m2) into 4 groups according to test results: OGTT+/SMBG+ (n=12, 11.7%); OGTT+/SMBG- (n=14, 13.6%); OGTT-/SMBG+ (n=9, 8.7%); and OGTT-/SMBG- (n=68, 66.0%). Clinical characteristics and maternal outcomes were statistically similar between groups. Neonatal complication rates were greater in groups with hyperglycemia than in the OGTT-/SMBG- group, notably neonatal hypoglycemia (9/12, 7/14, 5/9 vs. 6/68; p<0.001). Participants reported no convenience difference between methods but would prefer OGTT for a future pregnancy. CONCLUSIONS: More than half of the women with OGTT+ were normoglycemic in daily life. Conversely, 11.7% of women with OGTT- had pregnancy hyperglycemia. OGTT+ and/or SMBG+ were equally associated with greater neonatal complications. This study suggests that alongside OGTT, SMBG could improve the care of pregnant women.
Subject(s)
Diabetes, Gestational/diagnosis , Adult , Blood Glucose Self-Monitoring/psychology , Female , Glucose Tolerance Test/psychology , Humans , Pregnancy , Pregnancy Outcome , Prospective Studies , Young AdultABSTRACT
AIMS: To assess perceptions of patients using subcutaneous insulin infusion (CSII) about metabolic control, pump malfunctions, technical and insertion site adverse events (AEs) related to infusion sets/catheters as well as patients' practices. METHODS: Online survey (from June 2016 to January 2017) using an actualized 39-item questionnaire directed to adults with type 1 diabetes (T1D) using CSII therapy and living in the province of Quebec, Canada. RESULTS: Participants with T1D (nâ¯=â¯115, 72% females, 39.7⯱â¯14.0â¯years, diabetes duration: 20.9⯱â¯12.2â¯years, CSII use: 6.2⯱â¯4.1â¯years) adequately completed the survey. Infusion sets were changed every 3.3⯱â¯0.9â¯day. Improved glucose control and decreased number/severity of hypoglycemic episodes were reported by 80% and 68%/50% of subjects, respectively. Over the past year of CSII use, participants perceived no increase in anxiety/worry (84%), no negative impact on life (89%) or on time off from work/school (82%). Conversely, many experienced at least one clinical AEs at insertion site [pain (84%), adhesion (76%), irritation (69%), lipodystrophy (45%)] and technical issues [blockage (52%), cannula kinking (50%), pump stop (55%), air bubbles (46%)]. No significant association was observed between catheter wear-time and AEs. All participants had one or more problems related to CSII use, although only 37% reported addressing these issues with health professionals. CONCLUSION: Our study suggests that patients positively perceived CSII use although they experienced a high frequency of clinical and technical AEs. This warrants further attention by health professionals, investigators and manufacturers to optimize CSII therapy.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/psychology , Hypoglycemic Agents/administration & dosage , Insulin Infusion Systems , Insulin/administration & dosage , Adult , Canada/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Female , Humans , Injections, Subcutaneous , Male , Perception , Surveys and QuestionnairesABSTRACT
Increasing proportions of patients with diabetes use continuous subcutaneous insulin infusion (CSII) therapy mostly due to its clinical efficacy and flexibility for insulin dosing and adjustments. Some challenges are nevertheless associated with this technology. A key and underlooked component of CSII technical difficulties is the subcutaneous catheter used to infuse insulin. Several adverse events (AEs) have been experienced by patients in relation to catheters, such as blockage, kinking, and insertion site reactions, including irritation, infections, lipohypertrophies etc., all of which could compromise the metabolic control. With the objective of minimizing these AEs, recommendations for changing catheters every 2-3 days have historically been provided by manufacturers based on reports derived from small studies and anecdotal data. The aim of this review was to provide an updated analysis of current recommendations and patients' practices in relation to frequency of catheter change. Our main findings are: (1) adequately designed and powered studies investigating optimal catheter wearing time are still lacking; (2) increasing catheter wearing time is generally associated with increased frequency of catheter AEs; (3) however, interpatient variability is large, with some individuals needing to change their catheters every 2-3 days, whereas others probably being able to keep them in place for longer periods without problems. Further research is thus warranted to provide more solid and evidence-based recommendations while exploring personalized approaches at the same time. Increasing catheter wear life without significant side effects is an important goal to simplify CSII therapy and reduce its associated costs and burdens.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems/adverse effects , Lipodystrophy/etiology , Subcutaneous Tissue/drug effects , Humans , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The goal was to evaluate whether there was neurodevelopmental deficits in newborns born to mothers with gestational diabetes mellitus (GDM) compared to control newborns born to healthy mothers. METHODS: Forty-six pregnant women (21 controls and 25 GDM) were recruited. Electroencephalogram (EEG) was recorded in the newborns within 48â¯h after birth. The EEG signal was quantitatively analyzed using power spectral density (PSD); coherence between hemispheres was calculated in paired channels of frontal, temporal, central and occipital regions. RESULTS: The left centro-occipital PSD in control newborns was 12% higher than in GDM newborns (pâ¯=â¯0.036) but was not significant after adjustment for gestational age. While coherence was higher in the frontal regions compared to the occipital regions (pâ¯<â¯0.001), there was no difference between the groups for the fronto-temporal, frontal-central, centro-occipital and tempo-occipital regions. CONCLUSION: Our results support that EEG differences between groups were mainly modified by gestational age and less by GDM status of the mothers. However, there is a need to confirm this result with a higher number of mother-newborns. Quantitative EEG in GDM newborns within 48â¯h after birth is feasible. This study emphasizes the importance of controlling blood glucose during GDM to protect infant brain development.
Subject(s)
Brain Waves/physiology , Diabetes, Gestational/physiopathology , Electroencephalography , Adolescent , Adult , Female , Humans , Infant, Newborn , Pilot Projects , Pregnancy , Spectrum Analysis , Statistics, Nonparametric , Young AdultABSTRACT
BACKGROUND: During pregnancy, maternal circulating leptin is released by maternal adipose tissue and the placenta, and may have a role in fetal development. OBJECTIVES: We investigated maternal leptinemia and glycemia associations with neonatal adiposity, taking into account pregravid weight status. METHODS: We included 235 pregnant women from the Genetics of Glucose Regulation in Gestation and Growth prospective cohort with data: blood samples collected during the 2nd trimester, an oral glucose tolerance test (OGTT), and the measured leptin and glucose levels. As an integrated measure of maternal leptin exposure, we calculated the area under the curve for maternal leptin at the OGTT (AUCleptin). Within 72 h of delivery, we measured the triceps, biceps, subscapular, and suprailiac skinfold thicknesses (SFTs); the sum of these SFTs represented neonatal adiposity. We conducted a regression analysis to assess the maternal metabolic determinants of neonatal adiposity, adjusting for parity, smoking status, maternal triglyceride levels, gestational weight gain, placental weight, delivery mode, neonate sex, and gestational age at delivery. RESULTS: The pregravid BMI of the participating women was 23.3 (21.2-27.0). In the 2nd trimester, maternal AUCleptin was 1,292.0 (767.0-2,222.5) (ng × min)/mL, and fasting glucose levels were 4.2 ± 0.4 mmol/L. At delivery, the neonatal sum of 4 SFTs was 17.9 ± 3.3 mm. Higher maternal leptinemia was associated with higher neonatal adiposity (ß = 4.23 mm [SE = 1.77] per log-AUCleptin; p = 0.02) in mothers with a BMI ≥25, independently of confounders and maternal glycemia, but not in mothers with a BMI <25. Higher maternal fasting glucose was associated with higher neonatal adiposity (ß = 0.88 mm [SE = 0.30] per SD glucose; p = 0.005) in mothers with a BMI <25, independently of confounders and maternal leptinemia. CONCLUSION: Maternal leptinemia may be associated with neonatal adiposity in offspring from overweight/obese mothers, independently of maternal glycemia.
Subject(s)
Adiposity/physiology , Fetal Development/physiology , Leptin/blood , Mothers , Adult , Biomarkers/blood , Birth Weight/physiology , Blood Glucose/analysis , Body Mass Index , Female , Fetal Blood , Gestational Age , Glucose Tolerance Test , Humans , Infant, Newborn , Linear Models , Male , Pregnancy , Prospective Studies , Quebec , Young AdultABSTRACT
OBJECTIVE: To evaluate the fatty acid profile of cord blood phospholipids (PL), cholesteryl esters (CE), triglycerides (TG) and non-esterified fatty acids (NEFA) in neonates born to mothers with gestational diabetes mellitus (GDM) compared to non-diabetic mothers. METHODS: The offspring of 30 pregnant women (15 non-diabetic controls, 15 with diet- or insulin-controlled GDM) were recruited before delivery. Cord blood was collected. After lipid extraction, PL, CE, TG and NEFA were separated by thin layer chromatography and analysed by gas chromatography. RESULTS: In GDM vs. control mothers, maternal glycated haemoglobin (A1C, mean±SD) was not different between groups: 5.3±0.5% vs. 5.3±0.3% (p=0.757), respectively. Cord plasma fatty acids were not different in TG, CE and NEFA between GDM and non-diabetic mothers. However, in PL, levels of palmitate, palmitoleate, oleate, vaccinate and di-homo-gamma-linolenate were significantly lower, with a trend for lower arachidonate (p=0.078), in neonates born to GDM mothers compared to controls. CONCLUSION: In contrast to other studies on cord blood docosahexaenoic acid (DHA) levels in GDM mothers, we did not found lower levels of DHA in cord PL, CE, TG or NEFA in neonates born to GDM compared to non-diabetic mothers.
Subject(s)
Diabetes, Gestational/blood , Fatty Acids/analysis , Fetal Blood/chemistry , Adult , Cholesterol Esters/blood , Fatty Acids, Nonesterified/blood , Female , Humans , Infant, Newborn , Phospholipids/blood , Pregnancy , Triglycerides/blood , Young AdultABSTRACT
OBJECTIVE: Excessive gestational weight gain (GWG) is associated with increased birth weight and neonatal adiposity. However, timing of excessive GWG may have a differential impact on birth outcomes. The objective of this study was to compare the effect of early and mid/late excessive GWG on newborn anthropometry in the context of the Canadian clinical recommendations that are specific for first trimester and for second/third trimesters based on maternal pre-pregnancy BMI. METHODS: We included 607 glucose-tolerant women in our main analyses, after excluding women who had less than the recommended total GWG. Maternal body weight was measured in early pregnancy, mid-pregnancy, and late pregnancy. Maternal and fetal clinical outcomes were collected, including newborn anthropometry. Women were divided into four groups according to the Canadian guidelines for GWG in the first and in the second/third trimesters: (1) "overall non-excessive" (reference group); (2) "early excessive GWG"; (3) "mid/late excessive GWG"; and (4) "overall excessive GWG." Differences in newborn anthropometry were tested across GWG categories. RESULTS: Women had a mean (±SD) pre-pregnancy BMI of 24.7 ± 5.2 kg/m(2) and total GWG of 15.3 ± 4.4 kg. Women with mid/late excessive GWG gave birth to heavier babies (gestational age-adjusted birth weight z-score 0.33 ± 0.91) compared with women in the reference group (0.00 ± 0.77, P = 0.007), whereas women with early excessive GWG gave birth to babies of similar weight (gestational age-adjusted z-score 0.01 ± 0.86) to the reference group (0.00 ± 0.77, P = 0.84). When we stratified our analyses and investigated women who gained within the recommendations for total GWG, mid/late excessive GWG specifically was associated with greater newborn size, similar to our main analyses. CONCLUSION: Excessive GWG in mid/late pregnancy in women who did not gain weight excessively in early pregnancy is associated with increased birth size, even in those who gained within the Canadian recommendations for total GWG.
Subject(s)
Birth Weight/physiology , Body Weight/physiology , Pregnancy/statistics & numerical data , Weight Gain/physiology , Adult , Female , Gestational Age , Humans , Infant, Newborn , Male , Prospective Studies , Young AdultABSTRACT
BACKGROUND: Excessive gestational weight gain (GWG) is associated with adverse pregnancy outcomes. In non-pregnant populations, low leptin levels stimulate positive energy balance. In pregnancy, both the placenta and adipose tissue contribute to circulating leptin levels. We tested whether maternal leptin levels are associated with subsequent GWG and whether this association varies depending on stage of pregnancy and on maternal body mass index (BMI). METHODS: This prospective cohort study included 675 pregnant women followed from 1(st) trimester until delivery. We collected anthropometric measurements, blood samples at 1(st) and 2(nd) trimester, and clinical data until delivery. Maternal leptin was measured by ELISA (Luminex technology). We classified women by BMI measured at 1(st) trimester: BMI < 25 kg/m(2) = normal weight; 25 ≤ BMI < 30 kg/m(2) = overweight; and BMI ≥ 30 kg/m(2) = obese. RESULTS: Women gained a mean of 6.7 ± 3.0 kg between 1(st) and 2(nd) trimester (mid pregnancy GWG) and 5.6 ± 2.5 kg between 2(nd) and the end of 3(rd) trimester (late pregnancy GWG). Higher 1(st) trimester leptin levels were associated with lower mid pregnancy GWG, but the association was no longer significant after adjusting for % body fat (%BF; ß = 0.38 kg per log-leptin; SE = 0.52; P = 0.46). Higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG and this association remained significant after adjustment for BMI (ß = 2.35; SE = 0.41; P < 0.0001) or %BF (ß = 2.01; SE = 0.42; P < 0.0001). In BMI stratified analyses, higher 2(nd) trimester leptin levels were associated with greater late pregnancy GWG in normal weight women (ß = 1.33; SE = 0.42; P =0.002), and this association was stronger in overweight women (ß = 2.85; SE = 0.94; P = 0.003--P for interaction = 0.05). CONCLUSIONS: Our results suggest that leptin may regulate weight gain differentially at 1(st) versus 2(nd) trimester of pregnancy: at 2(nd) trimester, higher leptin levels were associated with greater subsequent weight gain--the opposite of its physiologic regulation in non-pregnancy--and this association was stronger in overweight women. We suspect the existence of a feed-forward signal from leptin in second half of pregnancy, stimulating a positive energy balance and leading to greater weight gain.
Subject(s)
Leptin/blood , Pregnancy Trimester, Second/blood , Weight Gain/physiology , Adult , Body Mass Index , Female , Humans , Overweight/blood , Pregnancy , Pregnancy Complications/blood , Pregnancy Trimester, First/blood , Prospective Studies , Risk FactorsABSTRACT
PURPOSE: We initiated the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort to increase our understanding of biological, environmental and genetic determinants of glucose regulation during pregnancy and their impact on fetal development. PARTICIPANTS: Between January 2010 and June 2013, we invited pregnant women aged ≥ 18 years old who visited the blood sampling in pregnancy clinic in Sherbrooke for their first trimester clinical blood samples: 1034 women accepted to participate in our cohort study. FINDINGS TO DATE: At first and second trimester, we collected demographics and lifestyle questionnaires, anthropometry measures (including fat and lean mass estimated using bioimpedance), blood pressure, and blood samples. At second trimester, women completed a full 75 g oral glucose tolerance test and we collected additional blood samples. At delivery, we collected cord blood and placenta samples; obstetrical and neonatal clinical data were abstracted from electronic medical records. We also collected buffy coats and extracted DNA from maternal and/or offspring samples (placenta and blood cells) to pursue genetic and epigenetic hypotheses. So far, we have found that low adiponectin and low vitamin D maternal levels in first trimester predict higher risk of developing gestational diabetes. FUTURE PLANS: We are now in the phase of prospective follow-up of mothers and offspring 3 and 5 years postdelivery to investigate the consequences of maternal dysglycaemia during pregnancy on offspring adiposity and metabolic profile. TRIAL REGISTRATION NUMBER: NCT01623934.
Subject(s)
Blood Glucose/metabolism , Diabetes, Gestational/epidemiology , Epigenesis, Genetic/genetics , Obesity/epidemiology , Vitamin D Deficiency/epidemiology , Adiponectin/metabolism , Adult , Body Composition , Body Mass Index , Canada/epidemiology , Diabetes, Gestational/metabolism , Female , Fetal Blood/metabolism , Glucose Tolerance Test , Humans , Infant, Newborn , Insulin Resistance , Male , Obesity/metabolism , Placenta/metabolism , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/metabolism , Prospective Studies , Risk Factors , Tumor Necrosis Factor-alpha/metabolism , Vitamin D/analogs & derivatives , Vitamin D/metabolism , Vitamin D Deficiency/metabolism , Young AdultSubject(s)
Goals , Insulin Infusion Systems , Diabetes Mellitus, Type 1 , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents , InsulinABSTRACT
Hypertensive disorders of pregnancy (HDP) lead to high rates of maternal and fetal morbidity. Existing studies on inflammatory marker TNFα in HDP offspring are inconsistent. We performed a population-based cohort study of 636 pregnancies, including normotensive (NT) women and women with preeclampsia (PE) or gestational hypertension (GH). TNFα was measured in maternal blood in the first and second trimesters and in cord blood at the time of delivery. Cord blood TNFα was higher in offspring delivered of women with PE (6.53 [4.94-8.38]pg/mL) versus those delivered of NT women (5.13 [4.11-6.72]pg/mL; p=0.01), independent of confounders. Maternal TNFα levels were not different among groups (p>0.1) in either the first or second trimester.
Subject(s)
Fetal Blood/metabolism , Pre-Eclampsia/blood , Tumor Necrosis Factor-alpha/blood , Adult , Female , Fetal Blood/immunology , Humans , Infant, Newborn , Pre-Eclampsia/immunology , PregnancyABSTRACT
Acetylcholine (Ach) has vasodilatory actions. However, data are conflicting about the role of Ach in regulating blood flow in subcutaneous adipose tissue (ATBF). This may be related to inaccurate ATBF recording or to the responder/nonresponder (R/NR) phenomenon. We showed previously that healthy individuals are R (ATBF increases postprandially by >50% of baseline BF) or NR (ATBF increases ≤50% postprandially). Our objective was to assess the role of the cholinergic system on ATBF in R and NR subjects. ATBF was manipulated by in situ microinfusion of vasoactive agents (VA) in AT and monitored by the (133)Xenon washout technique (both recognized methods) at the VA site and at the control site. We tested incrementally increasing doses of Ach (10(-5), 10(-3), and 10(-1) mol/l; n = 15) and Ach receptor antagonists (Ra) before and after oral administration of 75-g glucose using atropine (muscarinic Ra; 10(-4) mol/l, n = 13; 10(-5) mol/l, n = 22) and mecamylamine (nicotinic Ra; 10(-3) mol/l, n = 15; 10(-4) mol/l, n = 10). Compared with baseline [2.41 (1.36-2.83) ml·100 g(-1)·min(-1)], Ach increased ATBF dose dependently [3.32 (2.80-5.09), 6.46 (4.36-9.51), and 10.31 (7.98-11.52), P < 0.0001], with no difference between R and NR. Compared with control side, atropine (both concentrations) had no effect on fasting ATBF; only atropine 10(-4) mol/l decreased post-glucose ATBF [iAUC: 1.25 (0.32-2.91) vs. 1.98 (0.64-2.94); P = 0.04]. This effect was further apparent in R. Mecamylamine had no impact on fasting and postglucose ATBF in R and NR. Our results suggest that the cholinergic system is implicated in ATBF regulation, although it has no role in the blunting of ATBF response in NR.
Subject(s)
Acetylcholine/physiology , Receptors, Cholinergic/physiology , Regional Blood Flow/physiology , Subcutaneous Fat/blood supply , Acetylcholine/administration & dosage , Adult , Atropine/pharmacology , Blood Pressure/drug effects , Cholinergic Agents/pharmacology , Female , Heart Rate/drug effects , Humans , Male , Mecamylamine/pharmacology , Xenon Radioisotopes/pharmacokinetics , Young AdultABSTRACT
In Sherbrooke, the gestational diabetes mellitus (GDM) Regional Committee proposed GDM screening during the first trimester for all pregnant women based on a 50 g glucose challenge test (50 g GCT) followed directly by capillary self-monitoring blood glucose (SMBG) at home. We evaluated implementation of committee's recommendations on the clinical trajectory of women receiving prenatal care at our institution. We analyzed data collected systematically by the Blood Sampling in Pregnancy clinic from 2008 to 2011. We evaluated the clinical trajectory of 7710 pregnant women to assess GDM screening/diagnoses and referral rates to the diabetes care centre (DCC) for education and treatment during both the first and second trimesters. The Canadian Diabetes Association glycemic treatment targets in women with GDM were used as diagnosis thresholds and DCC referral decisions: Fasting glucose of 5.3 mmol/L and postprandial 2 h glucose of 6.7 mmol/L. We found that pregnant women were 28.0±4.8 years old, and their body mass indexes were 24.5±5.5 kg/m(2). During the first trimester, 47% of women were screened for GDM, mostly (84%) using the 50 g GCT. Following SMBG, 5.7% were referred to the DCC. Only 32% of women with early GDM had >1 GDM risk factor. Thereafter, 67% of normoglycemic women screened during the first trimester were screened again during the second trimester. Among women screened during the second trimester, most screening was done using 50 g GCT, and 8.8% were referred to the DCC following SMBG. Implementation of 50 g GCT testing followed by direct home SMBG was well implemented in our area. The importance of early GDM screening and rescreening during the second trimester still needs to be emphasized.
Subject(s)
Blood Glucose Self-Monitoring , Diabetes, Gestational/diagnosis , Adult , Diabetes, Gestational/epidemiology , Female , Glucose Tolerance Test , Humans , Practice Guidelines as Topic , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Prospective Studies , Quebec , Young AdultABSTRACT
OBJECTIVE: The lifetime risk of metabolic diseases in offspring of women with gestational diabetes mellitus (GDM) depends, at least in part, on the impact of glycemic fetal programming. To quantify this impact, we have developed and validated a unique mass spectrometry method to measure the percentage of glycated hemoglobin in cord blood. RESEARCH DESIGN AND METHODS: This case-control study includes 37 GDM women and 30 pregnant women with normal glucose tolerance (NGT). RESULTS: Glycation of the α-chain (Glα) was higher in neonates from GDM (2.32 vs. 2.20%, P < 0.01). Glα strongly correlated with maternal A1C measured at delivery in the overall cohort (r = 0.67, P < 0.0001) as well as in each group (GDM: r = 0.66, P < 0.0001; NGT: r = 0.50, P = 0.01). CONCLUSIONS: Thus, Glα may reflect hyperglycemic exposure during the last weeks of fetal development. Future studies will confirm Glα is a predictive biomarker of prenatally programmed lifetime metabolic health and disease.
Subject(s)
Diabetes, Gestational/blood , Fetal Hemoglobin/metabolism , Glycated Hemoglobin/metabolism , Hyperglycemia/blood , Metabolic Diseases/epidemiology , Prenatal Exposure Delayed Effects/blood , Adult , Blood Glucose/metabolism , Case-Control Studies , Female , Fetal Blood/metabolism , Fetal Development , Glycosylation , Humans , Infant, Newborn , Male , Metabolic Diseases/etiology , Pregnancy , Prenatal Exposure Delayed Effects/diagnosis , Young AdultABSTRACT
INTRODUCTION: TNFα is suspected to play a role in inflammation and insulin resistance leading to higher risk of metabolic impairment. Controversies exist concerning the role of TNFα in gestational insulin resistance. We investigated the interrelations between TNFα and insulin resistance in a large population-based cohort of pregnant women. METHODS: Women (n = 756) were followed prospectively at 5-16 weeks and 24-28 weeks of pregnancy. Anthropometric measures and blood samples were collected at both visits. A 75-g oral glucose tolerance test (OGTT) was conducted at the second trimester to assess insulin sensitivity status (homeostasis model of assessment of insulin resistance and Matsuda index). TNFα was measured at the first trimester (nonfasting) and at each time point of the OGTT. RESULTS: Participants were 28.4 ± 4.4 years old and had a mean body mass index of 25.5 ± 5.5 kg/m(2) at first trimester. Median TNFα levels were 1.56 (interquartile range, 1.18-2.06) pg/mL at first trimester and 1.61 (interquartile range, 1.12-2.13) pg/mL at second trimester (1 h after glucose load). At second trimester, higher TNFα levels were associated with higher insulin resistance index levels (r = 0.37 and -0.30 for homeostasis model of assessment of insulin resistance and Matsuda index, respectively; P < .0001), even after adjustment for age, body mass index, triglycerides, and adiponectin. Women with higher insulin resistance showed a continuing decrease in TNFα levels during the OGTT, whereas women who were more insulin sensitive showed an increase in TNFα at hour 1 and a decrease at hour 2 of the test. CONCLUSION: Higher insulin resistance is associated with higher levels of circulating TNFα at first and second trimesters of pregnancy. TNFα level dynamics during an OGTT at second trimester vary according to insulin-resistance state.
Subject(s)
Blood Glucose/metabolism , Diabetes, Gestational/diagnosis , Insulin Resistance/physiology , Tumor Necrosis Factor-alpha/blood , Adult , Diabetes, Gestational/blood , Female , Glucose Tolerance Test , Humans , PregnancyABSTRACT
The progressive increase of insulin resistance observed in pregnancy contributes to the pathophysiology of gestational diabetes mellitus (GDM). There is controversy whether vitamin D deficiency contributes to abnormal glycemic regulation in pregnancy. We tested the associations between first trimester 25-hydroxyvitamin D (25OHD) levels and: 1) the risk of developing GDM; 2) insulin resistance/sensitivity, beta cell function and compensation indices in a large population-based prospective cohort of pregnant women. Participants (n = 655) were seen at first (6-13 weeks) and second (24-28 weeks) trimesters for blood samples. At first trimester, 25OHD levels were measured. At second trimester, glucose and insulin were measured 3 times during the oral glucose tolerance test to estimate insulin resistance (HOMA-IR), beta cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUCins/gluc) and beta cell compensation (ISSI-2). Based on IADPSG criteria, 54 participants (8.2 %) developed GDM. Lower first trimester 25OHD levels were associated with higher risk of developing GDM even after adjustment for vitamin D confounding factors and GDM risk factors (OR = 1.48 per decrease of one SD in 25OHD levels; P = 0.04). Lower first trimester 25OHD levels were associated with higher HOMA-IR (r = - 0.08; P = 0.03), lower Matsuda index (r = 0.13; P = 0.001) and lower ISSI-2 (r = 0.08; P = 0.04). After adjustment for confounders, we found no significant association with HOMA-B and AUCins/gluc. Our results suggest that low levels of 25OHD at first trimester are (1) an independent risk factor for developing GDM and (2) associated with insulin resistance at second trimester.
Subject(s)
Diabetes, Gestational/etiology , Vitamin D Deficiency/complications , Adult , Blood Glucose/metabolism , China/epidemiology , Diabetes, Gestational/blood , Diabetes, Gestational/epidemiology , Female , Humans , Insulin/blood , Pregnancy , Pregnancy Trimester, First/blood , Prospective Studies , Risk Factors , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Young AdultABSTRACT
Adipose tissue (AT) is a very active organ, both metabolically and hormonally. These important functions depend on adequate blood flow (BF). Metabolic, hormonal, and vascular processes within AT are highly interconnected and any disruption will invariably impact the others. Therefore, any alteration of ATBF with obesity and/or insulin resistance will impact metabolic and hormonal AT functions. Similarly, metabolic or hormonal changes in AT will lead to ATBF disturbance. Thus, it is plausible that insufficient ATBF alters AT metabolic processes and response to regulatory signals, and may even aggravate the negative impacts of dysfunction in AT. The role of BF in AT metabolism can be evaluated by several techniques, but the xenon washout method is considered the "gold" standard. This technique can be combined with local microinfusion protocols, and the combination allows for precise assessment of mechanisms implicated in ATBF regulation.
Subject(s)
Adipose Tissue/blood supply , Regional Blood Flow/drug effects , Xenon/administration & dosage , Adipose Tissue/pathology , Humans , Insulin Resistance/genetics , Obesity/blood , Obesity/metabolism , Obesity/pathologyABSTRACT
OBJECTIVE: The use of a weight-based nomogram is considered as standard care for prescribing appropriate doses of unfractionated heparin (UFH). Because of the need for multiple other medications that may affect bleeding and that clinical data have relied on similar dosing algorithms, maximum initial bolus and infusion rates have been suggested (capped initial dose). Whether these weight-based heparin nomograms properly address therapeutic dosing in obese patients remains questionable. DESIGN AND METHODS: Thirty patients treated for acute coronary syndrome and weighing ≥110 kg were retrospectively compared with 90 controls (three groups of 30 patients, weighting 50-69.9, 70-89.9, or 90-109.9 kg), all treated with UFH, July 2008 to April 2009. The primary end point was the time required to obtain a threshold activated partial thromboplastin time (aPTT). RESULTS: Mean time to achieve threshold aPTT was longer for obese patients weighing ≥110 kg than for controls (31.47 vs. 12.89 hours; P < 0.0001). At 24 hours, 63% of obese patients weighing ≥110 kg had not reached threshold aPTT vs. 7% of controls (P < 0.0001). However, threshold infusion rate did not differ between weight categories (13.0 vs. 13.1 U/kg/h; P = NS) and approximated the initial infusion rate recommended by nomograms without applying the dose cap (12 U/kg/h). CONCLUSIONS: Adequate anticoagulation time doubled in patients weighing ≥110 kg, suggesting that these patients were not receiving appropriate heparin doses initially to achieve threshold aPTT rapidly. Using initial infusion rate recommended by a nomogram without capping for total body weight is suggested as acceptable in this study. This approach should be further evaluated in a prospective study.