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Glypican-4 in pregnancy and its relation to glucose metabolism, insulin resistance and gestational diabetes mellitus status.

ABSTRACT: Glypican-4 (GPC-4) is an adipokine that enhances insulin receptor signaling. Plasma concentrations were found to be elevated in patients with prediabetes but reduced in type 2 diabetes mellitus. No study on Glypican-4 in pregnancy and pregnancy-related insulin resistance has been published yet. GPC-4 levels were investigated in 59 overweight women throughout their pregnancy at the Medical University of Vienna. GPC-4 levels, fasting insulin, fasting glucose, estradiol, liver and renal parameters, and markers of bone development were assessed before the < 21st week of gestation (GW), and at GW 35-37. GPC-4 levels increased from < 21 GW (mean = 2.38 pg/ml, SD = 0.68 pg/ml) to GW 35-37 (mean = 2.96 pg/ml, SD = 0.77 pg/ml, p < 0.001). At the same time, GPC-4 levels correlated negatively with estimated glomerular filtration rate (eGFR), serum protein and serum albumin levels and were positively related to creatinine and uric acid levels at GW 35-37. Concerning glucose metabolism, GPC-4 levels were inversely related to ISSI-2, fasting insulin and HOMA-IR, however, not significantly different between women with normal glucose tolerance (NGT) and GDM (p = 0.239). In conclusion, GPC-4 levels rose significantly during pregnancy, correlated negatively with fasting insulin and HOMA-IR but might not be related to gestational diabetes mellitus status.

SUBMITTER: Deischinger C

PROVIDER: S-EPMC8668887 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Secretagogin is Related to Insulin Secretion but Unrelated to Gestational Diabetes Mellitus Status in Pregnancy.

Project description:Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (rp = 0.220, p = 0.032) and second phase index (rp = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum: 88.07 ± 35.63 pg/mL; pregnancy: 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (rp = 0.308; p = 0.021) and triglycerides (rp = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.

| S-EPMC7408624 | biostudies-literature

Genetic Studies of Gestational Diabetes and Glucose Metabolism in Pregnancy.

Project description:Purpose of reviewIn this review, we summarize studies investigating genetics of gestational diabetes mellitus (GDM) and glucose metabolism in pregnancy. We describe these studies in the context of the larger body of literature on type 2 diabetes (T2D) and glycemic trait genomics.Recent findingsWe reviewed 23 genetic association studies for GDM and performed a meta-analysis, which revealed variants at eight T2D loci significantly associated with GDM after the Bonferroni correction. These studies suggest that GDM and T2D share a number of genetic risk loci. Only two unbiased genome-wide association studies (GWASs) have successfully revealed genetic associations for GDM and related glycemic traits in pregnancy. A GWAS for GDM in Korean women identified two loci (near CDKAL1 and MTNR1B) known to be associated with T2D, though the association of the MTNR1B locus with GDM appears to be stronger than that for T2D. A multi-ethnic GWAS for glycemic traits in pregnancy identified two novel loci (near HKDC1 and BACE2) which appear to be associated with post-load glucose and fasting c-peptide specifically in pregnant women. There are ongoing efforts to use this genetic information, in the form of polygenic scores, to predict risk of GDM and postpartum T2D. The body of literature examining genetic associations with GDM is limited, especially when compared to the available literature on T2D and glycemic trait genomics. Additional genetic discovery for glucose metabolism in pregnant women will require larger pregnancy cohorts and international collaborative efforts. Studies on the clinical implications of these findings are also warranted.

| S-EPMC8132191 | biostudies-literature

Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism.

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| S-EPMC6385693 | biostudies-literature

A longitudinal study of thyroid markers during pregnancy and the risk of gestational diabetes mellitus and post-partum glucose metabolism.

Project description:AimsTo determine the relationship between thyroid markers during pregnancy and gestational diabetes mellitus (GDM) or post-partum glucose metabolism.Materials and methodsBased on pregnancy 75-g oral glucose tolerance test (OGTT) results, 1467 subjects were grouped into normal glucose tolerance (NGTp; n = 768) and GDM (n = 699) groups. Furthermore, based on post-partum 75-g OGTT results, 286 GDM subjects, screened for glucose metabolism after delivery, were grouped into NGTd (n = 241) and abnormal glucose tolerance (AGT; n = 45) groups.ResultsMaternal age, family history of diabetes, acanthosis nigricans, previous adverse pregnancy outcomes and caesarean section incidence, and thyroid positive antibody rates were higher in the GDM group than in the NGTp group. In the first trimester, free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were higher in the GDM group than in the NGTp group. In the second trimester, free thyroxine (FT4) levels were lower and TPOAb and TgAb levels were higher in the GDM group than in the NGTp group. After adjusting for confounding factors, FT3, TPOAb and TgAb (first trimester), and FT4, TPOAb and TgAb (second trimester) were risk factors for GDM. TPOAb and TgAb levels were higher in the AGT group than in the NGTd group and were potential predictors of abnormal post-partum glucose tolerance.ConclusionsGDM risk significantly increased with increased FT3 (first trimester), TPOAb and TgAb (first and second trimesters) or with decreased FT4 (second trimester). Presence of thyroid antibodies predicted post-partum glucose abnormalities in subjects with GDM.

| S-EPMC8243952 | biostudies-literature

Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

Project description:BACKGROUND/AIMS:The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). METHODS:A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ? 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). RESULTS:The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index ?-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ? 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p < 0.001 for all). Among the GIGT subjects, the 1-hour plasma glucose abnormal levels group showed significantly greater weight gain during pregnancy and higher values in the 50-g OGCT than the other two groups. Moreover, the 1-hour and 2-hour abnormal levels groups had poorer insulin secretion status than the 3-hour abnormal levels group. CONCLUSIONS:Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both ?-cell dysfunction and insulin resistance.

| S-EPMC3654128 | biostudies-literature

High Fasting Plasma Glucose during Early Pregnancy: A Review about Early Gestational Diabetes Mellitus.

Project description:Fasting plasma glucose (FPG) is nowadays routinely measured during early pregnancy to detect preexisting diabetes (FPG ≥ 7 mmol/L). This screening has concomitantly led to identify early intermediate hyperglycemia, defined as FPG in the 5.1 to 6.9 mmol/L range, also early gestational diabetes mellitus (eGDM). Early FPG has been associated with poor pregnancy outcomes, but the recommendation by the IADPSG to refer women with eGDM for immediate management is more pragmatic than evidence based. Although eGDM is characterized by insulin resistance and associated with classical risk factors for type 2 diabetes and incident diabetes after delivery, it is not necessarily associated with preexisting prediabetes. FPG ≥ 5.1 mmol/L in early pregnancy is actually poorly predictive of gestational diabetes mellitus diagnosed after 24 weeks of gestation. An alternative threshold should be determined but may vary according to ethnicity, gestational age, and body mass index. Finally, observational data suggest that early management of intermediate hyperglycemia may improve prognosis, through reduced gestational weight gain and potential early introduction of hypoglycemic agents. Considering all these issues, we suggest an algorithm for the management of eGDM based on early FPG levels that would be measured in case of risk factors. Nevertheless, interventional randomized trials are still missing.

| S-EPMC5664285 | biostudies-literature

The relationship between iron metabolism, stress hormones, and insulin resistance in gestational diabetes mellitus.

Project description:AIM:To analyze the relationship between iron metabolism index and stress hormones, insulin resistance, and oxidative stress in gestational diabetes mellitus (GDM). METHODS:From January to November 2019, 75 patients with GDM were selected as GDM group, according to age of 1:1; 75 normal pregnant women were selected as Control group. Blood glucose, insulin, stress hormones such as cortisol, norepinephrine (NE), and epinephrine (E), and iron metabolism index such as serum iron, serum ferritin (SF), and transferrin saturation (TS) were measured. Insulin resistance was evaluated by homeostasis model insulin resistance index (HOMA-IR). Multiple linear regression was used to analyze the relationship between iron metabolism index and stress hormones, insulin resistance, and oxidative stress. RESULTS:The levels of NE, E, serum iron, SF, and TS saturation in the GDM group were higher than Control group (t?=?3.82, 2.75, 3.14, 6.12, and 3.90, P?<?0.05, <0.05, <0.05, <0.01, <0.01); HOMA-IR was higher in the GDM group (t?=?4.92, P?<?0.01); malondialdehyde (MDA) was higher, while superoxide dismutase (SOD) was lower than Control group (t?=?5.25, 4.98, both P?<?0.01). Epinephrine, norepinephrine, cortisol, and serum ferritin were positively correlated (r?=?0.21, 0.17, and 0.21); epinephrine, cortisol, and transferrin were positively correlated (r?=?0.12, 0.31). There was a positive correlation between HOMA-IR and SF and TS (r?=?0.34, 0.34). MDA was positively correlated with SF and TS (r?=?0.24, 0.29); SOD was negatively related to SF and TS (r?=?-0.12, -0.17). CONCLUSIONS:Iron metabolism index is related to insulin resistance in GDM women. The change in iron metabolism may be involved in the pathogenesis of gestational diabetes caused by stress- adaptive disorder.

| S-EPMC7280284 | biostudies-literature

Maternal height, gestational diabetes mellitus and pregnancy complications.

Project description:AimsTo explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups.MethodsWomen from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height.ResultsUsing WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women.ConclusionsOnly taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.

| S-EPMC7611603 | biostudies-literature

Metformin versus Insulin in the Management of Pre-Gestational Diabetes Mellitus in Pregnancy and Gestational Diabetes Mellitus at the Korle Bu Teaching Hospital: A Randomized Clinical Trial.

Project description:ObjectiveTo determine if metformin monotherapy or metformin in combination with insulin is equally effective as insulin monotherapy at glycemic control in diabetes mellitus in pregnancy among Ghanaians.MethodsThis was a study involving 104 pregnant women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) at 20-30 weeks gestation. Participants were randomized into metformin and insulin treatment groups. Starting dose of metformin was 500 mg once a day and increased gradually over two (2) weeks, to meet glycemic targets. Insulin was added if targets could not be reached on metformin alone at maximum doses. Total daily dose of premixed insulin at initiation was calculated as 0.3 IU/kg body weight and titrated upwards to achieve glycemic control. Glycemic profile monitoring was done every two weeks.ResultsThe two hour post prandial blood glucose (2HPG) levels were significantly lower in the metformin group than the insulin group (p= 0.004).ConclusionThe findings of this study suggest that metformin monotherapy is effective in achieving glycemic targets in the management of diabetes in pregnancy. It is more effective than insulin in lowering the 2HPG level.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12614000942651.

| S-EPMC4422739 | biostudies-literature

Effect of Physical Activity during Pregnancy on Gestational Diabetes Mellitus.

Project description:Aims:The present study evaluates association between physical activity and Gestational Diabetes Mellitus (GDM), for it can be an effective intervention for its management. Though physical activity helps maintain glucose homeostasis, evidences of GDM risk are less extensive. Therefore, this study also identifies its correlation with maternal blood glucose levels. Materials and Methods:A prospective case-control study was carried out among pregnant women attending regular antenatal clinic at two private hospitals. The study comprised of 100 cases and 273 matched controls. Data was collected by personal interviews using a standard questionnaire. Physical activity was assessed using long form of International Physical Activity Questionnaire (IPAQ) reported as Metabolic Equivalent-Minutes per week (MET-Minutes/Week). Statistical Package for Social Sciences (SPSS) was used for analysis. Results:Results shows high exposure rates for low-to-moderate physical activity among cases, across all domains and sub-activities. The odds of GDM engaged in domestic and gardening activities for <2999 MET-minutes per week are 10 times higher than involved for ≥3000 MET-minutes per week (P < 0.001). The study also shows poor or no correlation between physical activity during pregnancy and maternal blood glucose levels. Conclusion:Despite existence of poor or no relationship with maternal blood glucose levels, prolonged sedentary behavior and decreased physical activities, especially domestic, are potential risk factors for GDM, a major finding of the study.

| S-EPMC6166569 | biostudies-other

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