Hyperglycemia and Adverse Pregnancy Outcomes Metzger, Boyd E; Coustan, Donald R; Trimble, Elisabeth R
Clinical chemistry (Baltimore, Md.),
07/2019, Letnik:
65, Številka:
7
Journal Article
Recenzirano
Odprti dostop
Associations of maternal fasting, 1-h, and 2-h 75-g OGTT values with primary study outcomes birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed ...neonatal hypoglycemia, and cordblood serum C-peptide above the 90th percentile were continuous. The data from the HAPO Study became the primary basis for the development of pregnancy outcome-based GDM criteria by the International Association of Diabetic Pregnancy Study Groups in 2010 (3), which have been incorporated into practice in many, but not all, parts of the world. Because of the change from requiring 1 instead of 2 increased glucose values, use of these new criteria has increased the prevalence of GDM, consistent with the worldwide epidemic of obesity and type 2 diabetes. Fax 312-503-0037; e-mail bem@northwestern.edu. 4 This article has been cited more than 2000 times since publication. 5 Nonstandard abbreviations: GDM, gestational diabetes mellitus; HAPO, Hyperglycemia and Adverse Pregnancy Outcomes (Study); OGTT, oral glucose tolerance test.
OBJECTIVE: To report frequencies of gestational diabetes mellitus (GDM) among the 15 centers that participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study using the new ...International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. RESEARCH DESIGN AND METHODS: All participants underwent a 75-g oral glucose tolerance test between 24 and 32 weeks’ gestation. GDM was retrospectively classified using the IADPSG criteria (one or more fasting, 1-h, or 2-h plasma glucose concentrations equal to or greater than threshold values of 5.1, 10.0, or 8.5 mmol/L, respectively). RESULTS: Overall frequency of GDM was 17.8% (range 9.3–25.5%). There was substantial center-to-center variation in which glucose measures met diagnostic thresholds. CONCLUSIONS: Although the new diagnostic criteria for GDM apply globally, center-to-center differences occur in GDM frequency and relative diagnostic importance of fasting, 1-h, and 2-h glucose levels. This may impact strategies used for the diagnosis of GDM.
To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.
Participants underwent a ...75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes.
Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m(2)), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93-2.47), for obesity alone 1.73 (1.50-2.00), and for both GDM and obesity 3.62 (3.04-4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women).
Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.
To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, ...thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity.
Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skin folds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex.
Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity, there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD.
These findings confirm the link between maternal glucose and neonatal adiposity and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biological relationship influencing fetal growth.
OBJECTIVE: To compare associations of maternal glucose and A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and determine, based on those ...comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance test (OGTT) in pregnant women. RESEARCH DESIGN AND METHODS: Eligible pregnant women underwent a 75-g OGTT at 24–32 weeks’ gestation. A sample for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with outcomes were assessed using multiple logistic regression with adjustment for potential confounders. RESULTS: Among 23,316 HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean ± SD A1C was 4.79 ± 0.40%. Associations were significantly stronger with glucose measures than with A1C for birth weight, sum of skinfolds, and percent body fat >90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01). For example, in fully adjusted models, odds ratios (ORs) for birth weight >90th percentile for each measure higher by 1 SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1-, and 2-h plasma glucose and 1.15 for A1C. ORs for cord C-peptide >90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. CONCLUSIONS: On the basis of associations with adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant women.
Hyperglycemia and Adverse Pregnancy Outcomes Metzger, Boyd E; Lowe, Lynn P; Dyer, Alan R ...
The New England journal of medicine,
05/2008, Letnik:
358, Številka:
19
Journal Article
Recenzirano
Odprti dostop
In this large, multinational study, glucose levels that were increased during pregnancy but were below levels diagnostic of diabetes were significantly associated with increased risks of birth weight ...above the 90th percentile and C-peptide levels above the 90th percentile, as well as with other adverse pregnancy outcomes. These results indicate the need to reconsider current thresholds for diagnosing and treating hyperglycemia during pregnancy.
Glucose levels that were increased during pregnancy but were below levels diagnostic of diabetes were significantly associated with increased risks of birth weight above the 90th percentile and C-peptide levels above the 90th percentile, as well as with other adverse pregnancy outcomes.
Gestational diabetes mellitus, defined as “glucose intolerance with onset or first recognition during pregnancy,”
1
,
2
has been the subject of considerable controversy. Criteria for the diagnosis were initially established more than 40 years ago
3
and, with minor modifications, remain in use today. These criteria are not designed to identify pregnant women who are at increased risk for adverse perinatal outcomes but rather women who are at high risk for the development of diabetes after pregnancy,
3
,
4
or they are the criteria used for the general population.
5
Overt diabetes mellitus during pregnancy is associated with significantly increased risks of adverse perinatal . . .
The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity.
A total of ...17,094 mothers and infants were included in the Hyperglycemia and Adverse Pregnancy Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and neonatal blood samples were collected. Biochemical neonatal hypoglycemia was defined as glucose levels of <10th percentile (2.2 mmol/L). Clinically identified hypoglycemia was ascertained through medical record review and associations were assessed.
Plasma glucose concentrations were stable during the first 5 hours after birth. Maternal glucose levels were weakly positively associated with biochemical neonatal hypoglycemia (odds ratios: 1.07-1.14 for 1-SD higher OGTT glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C-peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category). Larger and/or fatter infants were more likely to have hypoglycemia (P < .001), and infants with hypoglycemia tended to have a higher frequency of cord C-peptide levels of >90th percentile.
Mean neonatal plasma glucose concentrations varied little in the first 5 hours after birth, which suggests normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly related to maternal OGTT glucose measurements but were strongly associated with elevated cord serum C-peptide levels. Larger and/or fatter infants were more likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest physiologic relationships between maternal glycemia and fetal insulin production.
While there is increasing evidence for an altered clinical phenotype of Type 1 diabetes in several low-and middle-income countries, little is known about urban-rural differences and how the greater ...poverty of rural environments may alter the pattern of disease.
Investigation of urban-rural differences in demographic and anthropometric characteristics of type 1 diabetes in a resource-poor setting.
Analysis of a unique case register, comprising all patients (rural and urban) presenting with Type 1 diabetes over a 20 yr. period in a poor, geographically defined area in northwest Ethiopia. The records included age, sex, place of residence, together with height and weight at the clinical onset.
A total of 1682 new cases of Type 1 diabetes were registered with a mean age of onset of 31.2 (SD 13.4) yr. The patients were thin with 1/3 presenting with a body mass index (BMI) <17kg/m
. There was a striking male predominance of cases when clinical onset was between 20 and 35 yr., this was more marked in the very poor rural dwellers compared to the urban population. While most patients with Type 1 diabetes presented with low BMIs and reduced height, stunting preferentially affected rural men.
These data have led to the hypothesis that complex interactions among poor socioeconomic conditions in early life affect both pancreatic function and the development of autoimmunity and provide a possible explanation of the unusual phenotype of Type 1 diabetes in this very poor community.
Some have attributed risks of adverse outcomes associated with GDM, such as birth weight that is large for gestational age (LGA), excess fetal adiposity, and higher rate of cesarean section, to ...confounding characteristics, such as obesity, more advanced maternal age, or other medical complications, rather than glucose intolerance (7-9). ... it is likely that additional well-designed randomized controlled trials and other clinical studies will be needed to determine 1 cost-effective therapeutic strategies for treatment of GDM diagnosed by the IADPSG Consensus Panel-recommended criteria; 2 optimal glycemic treatment targets; 3 appropriate follow-up of mothers to determine risks for later development of diabetes, other metabolic disorders, or CVD risk factors; and 4 follow-up of children to assess potential associations of maternal glycemia with long-term risks of obesity, altered glucose metabolism, and CVD risk factors.
Aims/hypothesis
We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low ...autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations.
Methods
A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes (
n
= 236, ≤35 years) and control participants (
n
= 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and
HLA-DRB1
alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants.
Results
Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes.
HLA-DRB1*03:01
(
p
= 0.0014) and
HLA-DRB1*04
(
p
= 0.0001) were positively associated with this form of diabetes, while
HLA-DRB1*15
was protective (
p
< 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants (
p
= 1.60 × 10
−7
). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans.
Conclusions/interpretation
The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.
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