Infant feeding experiences among Indigenous communities in Canada, the United States, Australia, and Aotearoa: a scoping review of the qualitative literature.

BACKGROUND: Although exclusive breastfeeding is recommended for the first six months of life, research suggests that breastfeeding initiation rates and duration among Indigenous communities differ from this recommendation. Qualitative studies point to a variety of factors influencing infant feeding decisions; however, there has been no collective review of this literature published to date. Therefore, the objective of this scoping review was to identify and summarize the qualitative literature regarding Indigenous infant feeding experiences within Canada, the United States, Australia, and Aotearoa. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses- Scoping Reviews and the Joanna Briggs Institute Guidelines, in October 2020, Medline, Embase, CINAHL, PsycINFO, and Scopus were searched for relevant papers focusing on Indigenous infant feeding experiences. Screening and full-text review was completed by two independent reviewers. A grey literature search was also conducted using country-specific Google searches and targeted website searching. The protocol is registered with the Open Science Framework and published in BMJ Open. RESULTS: Forty-six papers from the five databases and grey literature searches were included in the final review and extraction. There were 18 papers from Canada, 11 papers in the US, 9 studies in Australia and 8 studies conducted in Aotearoa. We identified the following themes describing infant feeding experiences through qualitative analysis: colonization, culture and traditionality, social perceptions, family, professional influences, environment, cultural safety, survivance, establishing breastfeeding, autonomy, infant feeding knowledge, and milk substitutes, with family and culture having the most influence on infant feeding experiences based on frequency of themes. CONCLUSIONS: This review highlights key influencers of Indigenous caregivers' infant feeding experiences, which are often situated within complex social and environmental contexts with the role of family and culture as essential in supporting caregivers. There is a need for long-term follow-up studies that partner with communities to support sustainable policy and program changes that support infant and maternal health.

Determinants of Anishinabeck infant and early childhood growth trajectories in Northwestern Ontario, Canada: a cohort study.

BACKGROUND: The Developmental Origins of Health and Disease (DOHaD) paradigm emphasizes the significance of early life factors for the prevention of chronic health conditions, like type 2 diabetes (T2DM) and obesity, which disproportionately affect First Nations communities in Canada. Despite increasing DOHaD research related to maternal health during pregnancy, early childhood growth patterns, and infant feeding practices with many populations, data from First Nations communities in Canada are limited. In partnership with Sandy Lake First Nation, the aims of this project were to characterize birthweights and growth patterns of First Nations infants/children over the first 6 years of life and to study the impact of maternal and infant social and behavioral factors on birthweight and growth trajectories. METHODS: We recruited 194 families through community announcements and clinic visits. Infant/child length/height and weight were measured at 1 and 2 weeks; 1, 2, 6, 12, and 18 months; and 2, 3, 4, 5 and 6 years. Maternal and infant/child questionnaires captured data about health, nutrition, and social support. Weight-for-Age z-score (WAZ), Height-for-Age z-score (HAZ), and BMI-for-Age z-score (BAZ) were calculated using WHO reference standards and trajectories were analyzed using generalized additive models. Generalized estimating equations and logistic regression were used to determine associations between exposures and outcomes. RESULTS: WAZ and BAZ were above the WHO mean and increased with age until age 6 years. Generalized estimating equations indicated that WAZ was positively associated with age (0.152; 95% CI 0.014, 0.29), HAZ was positively associated with birthweight (0.155; 95% CI 0.035, 0.275), and BAZ was positively associated with caregiver's BMI (0.049; 95% CI 0.004, 0.090). There was an increased odds of rapid weight gain (RWG) with exposure to gestational diabetes (OR: 7.47, 95% CI 1.68, 46.22). Almost 70% of parents initiated breastfeeding, and breastfeeding initiation was modestly associated with lower WAZ (-0.18; 95% CI -0.64, 0.28) and BAZ (-0.23; 95% CI -0.79, 0.34). CONCLUSIONS: This work highlights early life factors that may contribute to T2DM etiology and can be used to support community and Indigenous-led prevention strategies.

Association of Visceral Adipose Tissue and Insulin Resistance with Incident Metabolic Syndrome Independent of Obesity Status: The IRAS Family Study.

OBJECTIVE: Although increasing evidence suggests that visceral adipose tissue (VAT) is a major underlying cause of metabolic syndrome (MetS), few studies have measured VAT at multiple time points in diverse populations. VAT and insulin resistance were hypothesized to differ by MetS status within BMI category in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study and, further, that baseline VAT and insulin resistance and increases over time are associated with incident MetS. METHODS: Generalized estimating equations were used for differences in body fat distribution and insulin resistance by MetS status. Mixed effects logistic regression was used for the association of baseline and change in adiposity and insulin resistance with incident MetS across 5 years, adjusted for age, sex, race/ethnicity, and family correlation. RESULTS: VAT and insulin sensitivity differed significantly by MetS status and BMI category at baseline. VAT and homeostatic model assessment of insulin resistance (HOMA-IR) at baseline (VAT odds ratio [OR] = 1.16 [95% CI: 1.12-2.31]; HOMA-IR OR = 1.85 [95% CI: 1.32-2.58]) and increases over time (VAT OR = 1.55 [95% CI: 1.22-1.98]; HOMA-IR OR = 3.23 [95% CI: 2.20-4.73]) were associated with incident MetS independent of BMI category. CONCLUSIONS: Differing levels of VAT may be driving metabolic heterogeneity within BMI categories. Both overall and abdominal obesity (VAT) may play a role in the development of MetS. Increased VAT over time contributed additional risk.

Influence of Preexisting Diabetes on Survival After a Breast Cancer Diagnosis in First Nations Women in Ontario, Canada.

PURPOSE: Survival after a breast cancer diagnosis is poorer in First Nations women with a preexisting comorbidity compared with comorbidity-free First Nations women in Ontario, Canada. Given the high prevalence of diabetes in this population, it is important to determine whether preexisting diabetes is related to poorer survival after a breast cancer diagnosis. METHODS: All First Nations women were identified from a cohort of First Nations people diagnosed with breast cancer in diagnostic periods-1995 to 1999 and 2000 to 2004-and seen at a regional cancer program (RCP) in Ontario. Preexisting diabetes status and other factors, such as age at diagnosis, body mass index, and stage at diagnosis, were collected from medical charts at the regional cancer programs. The association between preexisting diabetes and First Nations status was examined by each of the demographic, personal, tumor, and treatment factors using logistic regression models. Survival was compared between First Nations women with (n = 67) and without (n = 215) preexisting diabetes, adjusted by significant study factors using a Cox proportional hazards regression model. RESULTS: The 5-year survival rate among First Nations women with diabetes was 59.8% versus 78.7% among those without diabetes (P < .01). Preexisting diabetes significantly increased the risk of death among First Nations women with breast cancer (hazard ratio, 1.87; 95% CI, 1.12 to 3.13) after adjustment for age group, period of diagnosis, body mass index, other comorbidities at diagnosis, and stage. CONCLUSION: This study recommends awareness of this survival discrepancy among the treatment team for First Nations patients with breast cancer with preexisting diabetes.

Delayed timing of post-challenge peak blood glucose predicts declining beta cell function and worsening glucose tolerance over time: insight from the first year postpartum.

AIMS/HYPOTHESIS: On cross-sectional assessment, a delayed timing of the peak blood glucose level at ≥60 min post-challenge on an OGTT is associated with beta cell dysfunction. In this context, we hypothesised that longitudinal changes in the timing of this peak might predict changes in glucose metabolism. We thus sought to evaluate the longitudinal associations of changes in the timing of the peak glucose level with changes over time in insulin sensitivity, beta cell function and glucose tolerance. METHODS: A total of 532 women underwent an OGTT at both 3 months and 12 months postpartum. The participants were stratified into four groups according to the change in timing of their glucose peak between the two visits: women with no change in timing of the glucose peak at 30 min (n = 217), those whose glucose peak shifted to an earlier time point (n = 120), those whose peak shifted to a later time point (n = 87) and women with an unchanged glucose peak at ≥60 min (n = 108). Beta cell function was measured using the Insulin Secretion-Sensitivity Index-2 (ISSI-2). RESULTS: Compared with an unchanged glucose peak at 30 min, both the shift of the glucose peak to a later time point and a peak that was unchanged at ≥60 min were independently associated with declining ISSI-2 scores (ß = -127.5, p < 0.001 and ß = -98.8, p = 0.006, respectively) and increased 2 h post-challenge glucose levels (ß = 1.28, p < 0.001 and ß = 0.91, p < 0.001, respectively) between the two visits. Furthermore, both these patterns of change in peak were independently associated with worsening glucose tolerance (from normal to prediabetes [defined as impaired fasting glucose or impaired glucose tolerance]/diabetes or from prediabetes to diabetes) (OR 8.1, 95% CI 3.0, 22.1 and OR 3.7, 95% CI 1.2, 11.7, respectively). CONCLUSIONS/INTERPRETATION: A delayed timing of the post-challenge peak glucose level is associated with declining beta cell function and worsening glucose tolerance over time.

Insulin sensitivity and insulin clearance are heritable and have strong genetic correlation in Mexican Americans.

OBJECTIVE: The GUARDIAN (Genetics UndeRlying DIAbetes in HispaNics) consortium is described, along with heritability estimates and genetic and environmental correlations of insulin sensitivity and metabolic clearance rate of insulin (MCRI). METHODS: GUARDIAN is comprised of seven cohorts, consisting of 4,336 Mexican-American individuals in 1,346 pedigrees. Insulin sensitivity (SI ), MCRI, and acute insulin response (AIRg) were measured by frequently sampled intravenous glucose tolerance test in four cohorts. Insulin sensitivity (M, M/I) and MCRI were measured by hyperinsulinemic-euglycemic clamp in three cohorts. Heritability and genetic and environmental correlations were estimated within the family cohorts (totaling 3,925 individuals) using variance components. RESULTS: Across studies, age, and gender-adjusted heritability of insulin sensitivity (SI , M, M/I) ranged from 0.23 to 0.48 and of MCRI from 0.35 to 0.73. The ranges for the genetic correlations were 0.91 to 0.93 between SI and MCRI; and -0.57 to -0.59 for AIRg and MCRI (all P < 0.0001). The ranges for the environmental correlations were 0.54 to 0.74 for SI and MCRI (all P < 0.0001); and -0.16 to -0.36 for AIRg and MCRI (P < 0.0001-0.06). CONCLUSIONS: These data support a strong familial basis for insulin sensitivity and MCRI in Mexican Americans. The strong genetic correlations between MCRI and SI suggest common genetic determinants.

Fasting capillary glucose as a screening test for ruling out gestational diabetes mellitus.

OBJECTIVE: A common approach to screening for gestational diabetes mellitus (GDM) is the testing of all pregnant women with a one-hour, 50 g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) when the GCT is positive (≥ 7.8 mmol/L). As only a small subset of those with a positive GCT will have GDM, many more women undergo the OGTT than may be necessary. In this context, we hypothesized that measurement of fasting capillary glucose (FCG) could provide a strategy for reducing the number of unnecessary OGTTs. Thus, we sought to identify a threshold level of FCG below which GDM could be ruled out following a positive GCT, without need for the OGTT. METHODS: Following a positive GCT, 888 women underwent measurement of FCG prior to their OGTT. We evaluated the test characteristics of FCG for identifying the 209 women diagnosed with GDM on the OGTT. RESULTS: Fasting capillary glucose was positively associated with each glucose measurement on the OGTT (all P < 0.001) and inversely related to insulin sensitivity and pancreatic beta-cell function (both P < 0.001). As FCG increased, the prevalence of GDM progressively rose (P < 0.001). However, the area under the curve of the receiver-operating characteristic curve for FCG in predicting GDM was modest (0.67). Although using an FCG threshold of 4.8 mmol/L could reduce the number of OGTTs by 28.4%, this approach would miss 18.2% of cases of GDM. CONCLUSION: Fasting capillary glucose is associated with glycemia, insulin sensitivity, and pancreatic beta-cell function. However, a single FCG measurement is insufficient for reliably ruling out GDM after an abnormal GCT.

Objectif : Une approche courante pour le dépistage du diabète sucré gestationnel (DSG) consiste à soumettre toutes les femmes enceintes à une épreuve de charge en glucose (ECG, soit la glycémie une heure après l'ingestion de 50 g de glucose), suivie de la tenue d'une épreuve d'hyperglycémie provoquée par voie orale (EHPVO) diagnostique lorsque l'ECG s'avère positive (≥ 7,8 mmol/l). Puisque seul un faible sous-ensemble des femmes ayant obtenu des résultats positifs à l'ECG présenteront un DSG, un grand nombre de femmes sont donc inutilement soumises à une EHPVO. Dans ce contexte, nous avons émis l'hypothèse selon laquelle la mesure de la glycémie capillaire à jeun (GCJ) pourrait fournir une stratégie qui permettrait de réduire le nombre d'EHPVO menées inutilement. Ainsi, nous avons cherché à identifier un seuil de GCJ en deçà duquel la présence possible d'un DSG pourrait être écartée à la suite de l'obtention de résultats positifs à l'ECG, sans devoir avoir recours à l'EHPVO. Méthodes : Après avoir obtenu des résultats positifs à l'ECG, 888 femmes ont été soumises à la mesure de la GCJ avant la tenue d'une EHPVO. Nous avons évalué la valeur prévisionnelle de la GCJ pour ce qui est de l'identification des 209 femmes ayant obtenu un diagnostic de DSG à la suite de l'EHPVO. Résultats : La glycémie capillaire à jeun a été positivement associée à chacune des mesures de la glycémie obtenues au moyen de l'EHPVO (toutes P < 0,001) et s'est avérée inversement proportionnelle à l'insulinosensibilité et à la fonction des cellules ß pancréatiques (toutes deux P < 0,001). La GCJ s'est avérée directement proportionnelle à la prévalence du DSG (P < 0,001). Toutefois, la surface sous la courbe de la fonction d'efficacité du récepteur pour ce qui est de la valeur prévisionnelle de la GCJ en matière de DSG était modeste (0,67). Bien que l'utilisation d'un seuil de GCJ de 4,8 mmol/l puisse réduire le nombre de EHPVO de 28,4 %, 18,2 % des cas de DSG passeraient alors inaperçus. Conclusion : La glycémie capillaire à jeun est associée à la glycémie, à l'insulinosensibilité et à la fonction des cellules ß pancréatiques. Toutefois, une seule mesure de la GCJ ne s'avère pas suffisante pour écarter de façon fiable la présence possible du DSG à la suite de l'obtention de résultats anormaux à l'ECG.

Genetic analysis of adiponectin variation and its association with type 2 diabetes in African Americans.

OBJECTIVE: Adiponectin is an adipocytokine that has been implicated in a variety of metabolic disorders, including T2D and cardiovascular disease. Studies evaluating genetic variants in ADIPOQ have been contradictory when testing association with T2D in different ethnic groups. DESIGN AND METHODS: In this study, 18 SNPs in ADIPOQ were tested for association with plasma adiponectin levels and diabetes status. SNPs were examined in two independent African-American cohorts (nmax = 1,116) from the Insulin Resistance Atherosclerosis Family Study (IRASFS) and the African American-Diabetes Heart Study (AA-DHS). RESULTS: Five polymorphisms were nominally associated with plasma adiponectin levels in the meta-analysis (P = 0.035-1.02 × 10(-6) ) including a low frequency arginine to cysteine mutation (R55C) which reduced plasma adiponectin levels to <15% of the mean. Variants were then tested for association with T2D in a meta-analysis of these and the Wake Forest T2D case-control study (n = 3,233 T2D, 2645 non-T2D). Association with T2D was not observed (P ≥ 0.08), suggesting limited influence of ADIPOQ variants on T2D risk. CONCLUSIONS: Despite identification of variants associated with adiponectin levels, a detailed genetic analysis of ADIPOQ revealed no association with T2D risk. This puts into question the role of adiponectin in T2D pathogenesis: whether low adiponectin levels are truly causal for or rather a consequence.

Relationship of insulin sensitivity, insulin secretion, and adiposity with insulin clearance in a multiethnic population: the insulin Resistance Atherosclerosis study.

OBJECTIVE: We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS: We measured insulin sensitivity index (S(I)), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS: MCRI was positively related to S(I) and negatively to AIR and adiposity across sex, race/ethnicity populations, and varying states of glucose tolerance, adiposity, and family history of diabetes. Differences in MCRI by race/ethnicity (lower in African Americans and Hispanics compared with non-Hispanic whites) and glucose tolerance were largely explained by differences in adiposity, S(I), and AIR. CONCLUSIONS: Insulin sensitivity, insulin secretion, and adiposity are correlates of insulin clearance and appear to explain differences in insulin clearance by race/ethnicity and glucose tolerance status.

Estimating the contributions of rare and common genetic variations and clinical measures to a model trait: adiponectin.

Common genetic variation frequently accounts for only a modest amount of interindividual variation in quantitative traits and complex disease susceptibility. Circulating adiponectin, an adipocytokine implicated in metabolic disease, is a model for assessing the contribution of genetic and clinical factors to quantitative trait variation. The adiponectin locus, ADIPOQ, is the primary source of genetically mediated variation in plasma adiponectin levels. This study sought to define the genetic architecture of ADIPOQ in the comprehensively phenotyped Hispanic (n = 1,151) and African American (n = 574) participants from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Through resequencing and bioinformatic analysis, rare/low frequency (<5% MAF) and common variants (>5% MAF) in ADIPOQ were identified. Genetic variants and clinical variables were assessed for association with adiponectin levels and contribution to adiponectin variance in the Hispanic and African American cohorts. Clinical traits accounted for the greatest proportion of variance (POV) at 31% (P = 1.16 × 10-(47)) and 47% (P = 5.82 × 10-(20)), respectively. Rare/low frequency variants contributed more than common variants to variance in Hispanics: POV = 18% (P = 6.40 × 10-(15)) and POV = 5% (P = 0.19), respectively. In African Americans, rare/low frequency and common variants both contributed approximately equally to variance: POV = 6% (P = 5.44 × 10-(12)) and POV = 9% (P = 1.44 × 10-(10)), respectively. Importantly, single low frequency alleles in each ethnic group were as important as, or more important than, common variants in explaining variation in adiponectin. Cumulatively, these clinical and ethnicity-specific genetic contributors explained half or more of the variance in Hispanic and African Americans and provide new insight into the sources of variation for this important adipocytokine.

Association between ADIPOQ SNPs with plasma adiponectin and glucose homeostasis and adiposity phenotypes in the IRAS Family Study.

CONTEXT: Adiponectin is an adipocytokine associated with a variety of metabolic traits. These associations in human studies, in conjunction with functional studies in model systems, have implicated adiponectin in multiple metabolic processes. OBJECTIVE: We hypothesize that genetic variants associated with plasma adiponectin would also be associated with glucose homeostasis and adiposity phenotypes. DESIGN AND SETTING: The Insulin Resistance Atherosclerosis Family Study was designed to identify the genetic and environmental basis of insulin resistance and adiposity in the Hispanic- (n=1,424) and African-American (n=604) population. MAIN OUTCOME MEASURES: High quality metabolic phenotypes, e.g. insulin sensitivity (S(I)), acute insulin response (AIR), disposition index (DI), fasting glucose, body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and waist circumference, were explored. RESULTS: Based on association analysis of more than 40 genetic polymorphisms in the adiponectin gene (ADIPOQ), we found no consistent association of ADIPOQ variants with plasma adiponectin levels and adiposity phenotypes. However, there were two promoter variants, rs17300539 and rs822387, associated with plasma adiponectin levels (P=0.0079 and 0.021, respectively) in the Hispanic-American cohort that were also associated with S(I) (P=0.0067 and 0.013, respectively). In contrast, there was only a single promoter SNP, rs17300539, associated with plasma adiponectin levels (P=0.0018) and fasting glucose (P=0.042) in the African-American cohort. Strikingly, high impact coding variants did not show evidence of association. CONCLUSIONS: The lack of consistent patterns of association between variants, adiponectin levels, glucose homeostasis, and adiposity phenotypes suggests a reassessment of the influence of adiponectin in these pathways.

Impact of maternal physical activity and infant feeding practices on infant weight gain and adiposity.

Increasing evidence supports the contribution of intrauterine environmental exposures on obesity risk in offspring. Few studies have included maternal and infant lifestyle factors. Our objective was to study the impact of maternal physical activity, infant feeding, and screen time on offspring weight gain and adiposity. In a prospective cohort study, 246 mothers underwent testing during pregnancy to assess glucose tolerance status and insulin sensitivity. Anthropometry and questionnaires on physical activity, infant feeding, and screen time were completed. Multiple-linear regression was performed to examine the impact of maternal and infant factors on infant weight gain and weight-for-length z-score at 1 year. Infant weight outcomes were negatively predicted by maternal pregravid vigorous/sport index and exclusive breastfeeding duration. After adjustment, each unit increase in maternal pregravid vigorous/sport index decreased infant weight gain by 218.6 g (t = 2.44, P = 0.016) and weight-for-length z-score by 0.20 (t = 2.17, P = 0.031). Each month of exclusive breastfeeding reduced infant weight gain by 116.4 g (t = 3.97, P < 0.001) and weight-for-length z-score by 0.08 (t = 2.59, P = 0.01). Maternal pregravid physical activity and exclusive breastfeeding duration are associated with weight gain and adiposity as early as 1 year of age.

Circadian variation in the response to the glucose challenge test in pregnancy: implications for screening for gestational diabetes mellitus.

OBJECTIVE: A common approach to screening for gestational diabetes mellitus (GDM) is the universal testing of all pregnant women with a 1-h, 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those in whom the GCT is positive (≥7.8 mmol/L). More important, the GCT is performed at any time of day, but there has been limited study of the effect of time of day on test performance. Thus, using their subsequent OGTT (performed in the morning), we sought to characterize the metabolic function of women with positive GCTs in relation to the timing of their test. RESEARCH DESIGN AND METHODS: A total of 927 women with positive GCTs underwent a 3-h 100-g OGTT. They were stratified into four groups by time of day (hours) of their GCT: <0900 (n = 171), 0900-1059 (n = 288), 1100-1259 (n = 189), and ≥1300 (n = 279). RESULTS: On the OGTT, the prevalence of GDM progressively decreased across the GCT groups from <0900 h (26.9%) to 0900-1059 h (25.0%) to 1100-1259 h (21.7%) to ≥1300 h (21.5%; P = 0.0022). After adjustment for GDM risk factors, mean adjusted glucose area under the curve (AUC(gluc)) similarly decreased across the groups, while insulin sensitivity (Matsuda index) and ß-cell function (Insulin Secretion-Sensitivity Index-2) progressively increased (all P < 0.0001). In particular, compared with the <0900- and 0900-1059-h groups, women whose positive GCT occurred after 1300 h had superior metabolic function, as evidenced by lower AUC(gluc), higher insulin sensitivity, and better ß-cell function (all P ≤ 0.0097). CONCLUSIONS: Among women with a positive GCT, those tested in the afternoon have better metabolic function and a lower risk of GDM on subsequent OGTT.

Effect of maternal weight, adipokines, glucose intolerance and lipids on infant birth weight among women without gestational diabetes mellitus.

BACKGROUND: The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight. METHODS: We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery. RESULTS: The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05-1.27, per 1 kg/m(2) increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05-1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30-0.82, per 1 standard deviation change). INTERPRETATION: Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels.

Circulating levels of TNF-α are associated with impaired glucose tolerance, increased insulin resistance, and ethnicity: the Insulin Resistance Atherosclerosis Study.

OBJECTIVE: Although several epidemiological studies have investigated associations between TNF-α and insulin resistance, results have been inconsistent. We studied the relationship between TNF-α and glucose tolerance status as part of the Insulin Resistance Atherosclerosis Study. RESEARCH DESIGN AND METHODS: Serum concentrations of TNF-α were measured in 1558 individuals in a triethnic population across a spectrum of glucose tolerance. Insulin sensitivity and insulin secretion were assessed by a frequently sampled iv glucose tolerance test (FSIGT). RESULTS: Compared with those with normal glucose tolerance, circulating levels of TNF-α were elevated in individuals with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2D) after adjusting for age, gender, ethnicity, clinic site, and body mass index (3.3, 3.5, and 3.7 pg/ml in subjects with normal glucose tolerance, IGT, and T2D, respectively; P<0.05). Age-, sex-, and body mass index-adjusted levels of TNF-α differed by ethnicity, with Hispanics having the highest levels and African-Americans having the lowest (4.1, 3.6, and 3.0 pg/ml in Hispanics, non-Hispanic whites, and African-Americans, respectively; P<0.05). TNF-α was correlated with waist circumference, high-density lipoprotein, triglycerides, plasminogen activator inhibitor-1 and insulin sensitivity index (SI) (r=0.22, -0.30, 0.35, 0.31, and -0.25; P<0.0001); however, correlations varied by ethnicity. After adjusting for demographics and adiposity, individuals characterized by increased insulin resistance (lower SI), had higher levels of TNF-α than subjects characterized by high insulin sensitivity (3.8 and 3.3 pg/ml in subjects with an SI below/above the median at baseline; P<0.0001). No differences were found for acute insulin response. CONCLUSIONS: We confirm that TNF-α is associated with IGT and T2D in a large, multiethnic population, independent of measures of adiposity. Adjusted values of TNF-α, as well as relationships between TNF-α and variables related to T2D, varied by ethnicity. Increased TNF-α levels were predominantly associated with insulin resistance but not with primary defects in ß-cell function.

A socioecological framework to understand weight-related issues in Aboriginal children in Canada.

Obesity prevention efforts in Aboriginal (First Nations, Métis, or Inuit) communities in Canada should focus predominantly on children given their demographic significance and the accelerated time course of occurrence of type 2 diabetes mellitus in the Aboriginal population. A socioecological model to address childhood obesity in Aboriginal populations would focus on the numerous environments at different times in childhood that influence weight status, including prenatal, sociocultural, family, and community environments. Importantly, for Aboriginal children, obesity interventions need to also be situated within the context of a history of colonization and inequities in the social determinants of health. This review therefore advocates for the inclusion of a historical perspective and a life-course approach to obesity prevention in Aboriginal children in addition to developing interventions around the socioecological framework. We emphasize that childhood obesity prevention efforts should focus on promoting maternal health behaviours before and during pregnancy, and on breastfeeding and good infant and child nutrition in the postpartum and early childhood development periods. Ameliorating food insecurity by focusing on improving the sociodemographic risk factors for it, such as increasing income and educational attainment, are essential. More research is required to understand and measure obesogenic Aboriginal environments, to examine how altering specific environments modifies the foods that children eat and the activities that they do, and to examine how restoring and rebuilding cultural continuity in Aboriginal communities modifies the many determinants of obesity. This research needs to be done with the full participation of Aboriginal communities as partners in the research.

Postpartum metabolic function in women delivering a macrosomic infant in the absence of gestational diabetes mellitus.

OBJECTIVE: Gestational diabetes mellitus (GDM) is associated with fetal macrosomia and maternal postpartum dysglycemia, insulin resistance, and ß-cell dysfunction. Indeed, in practice, a prior pregnancy that resulted in a large-for-gestational-age (LGA) delivery is often considered presumptive evidence of GDM, whether or not it was diagnosed at the time. If this clinical assumption is correct, however, we would expect these women to exhibit postpartum metabolic dysfunction. Thus, to test this hypothesis, we assessed metabolic function during and after pregnancy in a cohort of women stratified according to the presence/absence of GDM and LGA delivery, respectively. RESEARCH DESIGN AND METHODS: A total of 562 women underwent metabolic characterization, including oral glucose tolerance test (OGTT), in late pregnancy and at 3 months' postpartum. The women were stratified into three groups: those with neither GDM nor LGA delivery (nonGDM, n = 364), those without GDM but with LGA delivery (nonGDM-LGA, n = 46), and those with GDM (n = 152). RESULTS: On logistic regression, GDM predicted postpartum glucose intolerance (OR 4.1 [95% CI 2.5-6.8]; P < 0.0001), whereas nonGDM-LGA did not (P = 0.65). At 3 months' postpartum, the mean adjusted levels of fasting glucose and area under the glucose curve on the OGTT were significantly higher in the GDM women compared with either nonGDM or nonGDM-LGA (all P < 0.05), with no differences between the latter two groups. In a similar manner, mean adjusted insulin sensitivity (Matsuda index) and ß-cell function (Insulin Secretion-Sensitivity Index-2) were lower in GDM women compared with either nonGDM or nonGDM-LGA (all P < 0.05), again with no differences between the latter two groups. CONCLUSIONS: Women with nonGDM-LGA do not exhibit postpartum metabolic dysfunction, arguing against the assumption of undiagnosed GDM in these patients.

Hepatic insulin resistance is an early determinant of declining ß-cell function in the first year postpartum after glucose intolerance in pregnancy.

OBJECTIVE The increased risk of type 2 diabetes in women with glucose intolerance in pregnancy is mediated by deterioration of their ß-cell function, which occurs as early as the first year postpartum. We thus sought to identify early determinants of their declining ß-cell function. RESEARCH DESIGN AND METHODS Women with recent gestational glucose intolerance (166) underwent oral glucose tolerance test at 3 and 12 months postpartum. They were stratified into those in whom ß-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]) declined over this time (decliners; n = 92) and those in whom it did not (nondecliners; n = 74). RESULTS Between 3 and 12 months, hepatic insulin sensitivity (1/homeostasis model assessment of insulin resistance [HOMA-IR]) decreased in decliners but not in nondecliners. Over this time, the change in 1/HOMA-IR emerged as an independent predictor of the change in ISSI-2 (t = 5.5; P < 0.0001). Increased hepatic insulin sensitivity independently predicted a lower likelihood of declining ß-cell function (odds ratio = 0.13 [95% CI 0.06-0.29]; P < 0.0001). CONCLUSIONS Hepatic insulin resistance is an early determinant of declining ß-cell function after gestational dysglycemia.

Adiponectin and the incidence of type 2 diabetes in Hispanics and African Americans: the IRAS Family Study.

OBJECTIVE: A recent meta-analysis of 13 prospective studies reported that higher levels of adiponectin were significantly associated with lower risk of type 2 diabetes. Most previous studies, however, were limited in their ability to adjust for appropriate confounding variables. Our objective, therefore, was to study this association after adjustment for directly measured adiposity and insulin sensitivity, expressed as the insulin sensitivity index (S(I)). RESEARCH DESIGN AND METHODS: The study included 1,096 Hispanic and African American participants free of diabetes at baseline (2000-2002) who returned for follow-up after 5 years. S(I) was determined from frequently sampled intravenous glucose tolerance tests with minimal model analysis. Visceral adipose tissue (VAT) area was determined by computed tomography. Diabetes and impaired fasting glucose (IFG) were defined using American Diabetes Association criteria. Multivariate generalized estimating equation logistic regression models were used to account for correlations within families. RESULTS: A total of 82 subjects met criteria for incident diabetes. After adjustment for age, sex, ethnicity, and smoking, adiponectin was significantly inversely associated with diabetes (odds ratio [OR] 0.54 per 1 SD difference [95% CI 0.38-0.76]). The association remained significant after additional adjustment in individual models for BMI, homeostasis model assessment of insulin resistance, or VAT (all P < 0.05). However, adiponectin was no longer associated in separate models adjusted for S(I) or IFG (OR 0.81 [0.56-1.16] and 0.75 [0.53-1.06], respectively). CONCLUSIONS: Adiponectin was inversely associated with incident diabetes after adjustment for conventional anthropometric and metabolic variables or VAT. Adjustment for detailed measures of S(I) attenuated this relationship, however, suggesting that the link between adiponectin and diabetes may operate at least in part through insulin resistance.