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.

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.

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.

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.

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.

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.

Low-dose combination therapy with rosiglitazone and metformin to prevent type 2 diabetes mellitus (CANOE trial): a double-blind randomised controlled study.

BACKGROUND: The evolving epidemic of type 2 diabetes has challenged health-care providers to assess the safety and efficacy of various diabetes prevention strategies. The CANOE (CAnadian Normoglycemia Outcomes Evaluation) trial investigated whether low-dose combination therapy would affect development of type 2 diabetes. METHODS: In this double-blind, randomised controlled trial undertaken in clinics in Canadian centres, 207 patients with impaired glucose tolerance were randomly assigned to receive combination rosiglitazone (2 mg) and metformin (500 mg) twice daily or matching placebo for a median of 3.9 years (IQR 3.0-4.6). Randomisation was computer-generated in blocks of four, with both participants and investigators masked to treatment allocation. The primary outcome was time to development of diabetes, measured by an oral glucose tolerance test or two fasting plasma glucose values of 7.0 mmol/L or greater. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00116932. FINDINGS: 103 participants were assigned to rosiglitazone and metformin, and 104 to placebo; all were analysed. Vital status was obtained in 198 (96%) participants, and medication compliance (taking at least 80% of assigned medication) was 78% (n=77) in the metformin and rosiglitazone group and 81% (n=80) in the placebo group. Incident diabetes occurred in significantly fewer individuals in the active treatment group (n=14 [14%]) than in the placebo group (n=41 [39%]; p<0.0001). The relative risk reduction was 66% (95% CI 41-80) and the absolute risk reduction was 26% (14-37), yielding a number needed to treat of 4 (2.70-7.14). 70 (80%) patients in the treatment group regressed to normal glucose tolerance compared with 52 (53%) in the placebo group (p=0.0002). Insulin sensitivity decreased by study end in the placebo group (median -1.24, IQR -2.38 to -0.08) and remained unchanged with rosiglitazone and metformin treatment (-0.39, -1.30 to 0.84; p=0.0006 between groups). The change in beta-cell function, as measured by the insulin secretion-sensitivity index-2, did not differ between groups (placebo -252.3, -382.2 to -58.0 vs rosiglitazone and metformin -221.8, -330.4 to -87.8; p=0.28). We recorded an increase in diarrhoea in participants in the active treatment group compared with the placebo group (16 [16%] vs 6 [6%]; p=0.0253). INTERPRETATION: Low-dose combination therapy with rosiglitazone and metformin was highly effective in prevention of type 2 diabetes in patients with impaired glucose tolerance, with little effect on the clinically relevant adverse events of these two drugs. FUNDING: GlaxoSmithKline.

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.

APOC1 T45S polymorphism is associated with reduced obesity indices and lower plasma concentrations of leptin and apolipoprotein C-I in aboriginal Canadians.

Apolipoprotein (apo) C-I is a constituent of chylomicrons, very low density lipoprotein, and high density lipoprotein. The role of apo C-I in human metabolism is incompletely defined. We took advantage of a naturally occurring amino acid polymorphism that is present in aboriginal North Americans, namely apo C-I T45S. We assessed the hypothesis that metabolic traits, including obesity-related and lipoprotein-related traits, would differ between carriers and noncarriers of apo C-I T45S. A genotyping assay was developed for APOC1 T45S and genotypes were determined in a sample of 410 Canadian Oji-Cree subjects. The allele frequency of the apo C-I S45 allele was approximately 8% in this sample. We observed the apo C-I S45 allele was significantly associated with 1) lower percent body fat (P < 0.05), 2) lower waist circumference (P = 0.058), 3) lower serum leptin levels (P < 0.05), and 4) lower plasma apo C-I levels (P < 0.0001), using a newly developed ELISA-based method. Taken together, these results suggest that at the whole human phenotype level, apo C-I is associated with the complex metabolic trait of obesity as well as with serum leptin levels.

Window to the brain: Can retinopathy be used to assess cognitive function.

OBJECTIVE: Retinopathy status as a screening method to predict cognitive health is limited. The objective of this study was to examine the association between retinopathy and lowered cognitive performance in a Canadian First Nations population. METHODS: Eligible individuals were assessed by the Clock Drawing Test (CDT) and the Trail Making Test Parts A and B, which were combined into an executive function score (TMT-exec). Digital fundus photographs were taken for both eyes to assess retinopathy. Anthropometric, vascular and metabolic risk factors were assessed by interview, clinical examinations and blood tests. Carotid atherosclerosis was assessed by Doppler ultrasonography. RESULTS: Retinopathy was detected in 7.1% of the population. Individuals classified as having a previous history of cardiovascular disease, insulin resistance and diabetes were more likely to have retinopathy. No other cardiovascular risk factors were associated. In unadjusted analysis, there were no associations between retinopathy and lowered cognitive performance (CDT, odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.30­2.53; TMT-exec, OR: 1.79, 95% CI: 0.60­5.33). Multivariable adjusted analysis also showed no associations, although sample size may be limiting. CONCLUSIONS: Retinopathy was not associated with lowered cognitive performance. Associations for microvascular risk factors suggest a panel of cognitive tests is needed for future studies.

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.

An abnormal screening glucose challenge test in pregnancy predicts postpartum metabolic dysfunction, even when the antepartum oral glucose tolerance test is normal.

OBJECTIVE: In pregnancy, a normal result on the oral glucose tolerance test (OGTT) that follows an abnormal screening glucose challenge test (GCT) is considered a reassuring finding, requiring no further intervention. The obstetrical and metabolic implications of this presentation, however, have not been well studied. Thus, we sought to characterize the obstetrical and postpartum metabolic significance of an abnormal GCT in women with normal glucose tolerance (NGT) on antepartum OGTT. DESIGN/PATIENTS/MEASUREMENTS: A total of 259 women with NGT on antepartum OGTT (166 with an abnormal GCT and 93 with a normal GCT) underwent (i) metabolic evaluation in pregnancy, (ii) assessment of obstetrical outcome at delivery and (iii) repeat metabolic characterization by OGTT at 3 months postpartum. RESULTS: Neither infant birthweight nor Caesarean section rate differed between the abnormal GCT and normal GCT groups. At 3 months postpartum, however, compared to the normal GCT group, the abnormal GCT group exhibited greater glycaemia (mean area under the glucose curve (AUC(gluc)) 19.6 vs. 18.3, P = 0.0021), lower insulin sensitivity (median insulin sensitivity index (IS(OGTT)) 9.5 vs. 11.3, P = 0.0243) and poorer beta-cell function (median insulinogenic index/Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) 9.8 vs. 14.1, P = 0.0013). On multiple linear regression analyses, an abnormal GCT emerged as (i) the strongest independent predictor of postpartum AUC(gluc) (t = 2.77, P = 0.006) and (ii) the strongest independent negative predictor of log insulinogenic index/HOMA-IR (t = -2.36, P = 0.0191). Furthermore, the GCT was the antepartum parameter that best predicted postpartum pre-diabetes (area under the receiver operating characteristic curve (AROC) = 0.754). CONCLUSIONS: An abnormal antepartum GCT, even when followed by a normal OGTT, is associated with postpartum glycaemia and beta-cell dysfunction, factors that may portend an increased future risk of diabetes in this patient population.

Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

OBJECTIVE: Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. DESIGN/PATIENTS/MEASUREMENTS: A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. RESULTS: Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P < 0.0001). Furthermore, on multiple linear regression analysis, pre-gravid vigorous/sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P < 0.0001). CONCLUSIONS: Pre-gravid vigorous/sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

Metabolic syndrome and its components as predictors of incident type 2 diabetes mellitus in an Aboriginal community.

BACKGROUND: Risk factors for type 2 diabetes remain poorly characterized among Aboriginal Canadians. We aimed to determine the incidence of type 2 diabetes in an Aboriginal community and to evaluate prospective associations with metabolic syndrome and its components. METHODS: Of 606 participants in the Sandy Lake Health and Diabetes Project from 1993 to 1995 who were free of diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipid levels were measured. Fasting and 2-hour postload glucose levels were obtained at follow-up to determine incident cases of type 2 diabetes. RESULTS: The 10-year cumulative incidence of diabetes was 17.5%. High adiposity, dyslipidemia, hyperglycemia, hyperinsulinemia and hypertension at baseline were associated with an increased risk of diabetes after adjustment for age and sex (all p < or = 0.03). Metabolic syndrome had high specificity (75%-88%) and high negative predictive value (85%-87%) to correctly detect diabetes-free individuals at follow-up. It had low sensitivity (26%-48%) and low positive predictive value (29%-32%) to detect future diabetes. Metabolic syndrome at baseline was associated with incident diabetes after adjustment for age and sex, regardless of whether the syndrome was defined using the National Cholesterol Education Program criteria (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.10-3.75) or the International Diabetes Federation criteria (OR 2.14, 95% CI 1.29-3.55). The association was to the same degree as that for impaired glucose tolerance assessed using the oral glucose tolerance test (OR 2.87, 95% CI 1.52-5.40; p > 0.05 for comparison of C statistics). INTERPRETATION: Metabolic syndrome and its components can be identified with readily available clinical measures. As such, the syndrome may be useful for identifying individuals at risk of type 2 diabetes in remote Aboriginal communities.

Correlation of circulating full-length visfatin (PBEF/NAMPT) with metabolic parameters in subjects with and without diabetes: a cross-sectional study.

OBJECTIVE: Here we use a novel ELISA that is specific for full-length visfatin (PBEF/NAMPT), compare it with the existing C-terminal based assay and use it to investigate associations of visfatin with metabolic parameters. DESIGN, PATIENTS AND MEASUREMENTS: We established the specificity and effectiveness of the new ELISA and evaluated the associations of full-length visfatin with clinical, anthropometric and metabolic parameters in a cross-sectional study of 129 Thai subjects, consisting of 50 outpatients with type 2 diabetes and 79 healthy volunteers. RESULTS: The new ELISA accurately recovered full-length recombinant visfatin and detected visfatin secreted by primary human and rat adipocytes. We found serum full-length visfatin was significantly higher in subjects with diabetes compared to their nondiabetic peers (median 2.75 vs. 2.22 ng/ml, P = 0.0142). After adjustment for age, gender and traditional metabolic risk factors, adjusted mean visfatin remained significantly higher in the diabetes group (3.80 vs. 2.10 ng/ml, P = 0.0021). On Spearman univariate correlation analysis, visfatin was significantly associated with resistin (r = 0.30, P = 0.0011), but not with any other anthropometric or metabolic variables, including adiponectin multimers. On multiple linear regression analysis, the only covariates independently associated with visfatin were diabetes (t = 3.11, P = 0.0024) and log resistin (t = 2.68, P = 0.0086). CONCLUSIONS: Circulating visfatin is independently associated with diabetes and resistin concentration, but is not related to adiponectin multimers or other metabolic covariates. These data are suggestive of a potential role of visfatin in subclinical inflammatory states.

Maternal obesity and familial history of diabetes have opposing effects on infant birth weight in women with mild glucose intolerance in pregnancy.

OBJECTIVE: Pregnant women with an abnormal screening glucose challenge test (GCT) but without gestational diabetes mellitus (GDM) on subsequent oral glucose tolerance test (OGTT) are at increased risk of delivering macrosomic and large for gestational age (LGA) neonates. We thus sought to evaluate the maternal constitutional and biochemical factors that determine infant birth weight in this patient population. METHODS: Women with an abnormal GCT were evaluated at the time of their OGTT in late pregnancy. This analysis was restricted to Caucasian women without GDM (N = 86). Maternal demographic and biochemical factors were evaluated in relation to infant birth weight and LGA. RESULTS: After adjustment for length of gestation, birth weight was positively associated with pre-pregnancy body mass index (BMI) (r = 0.31, p = 0.0063) and negatively correlated with maternal serum levels of the insulin-sensitizing protein adiponectin (r = -0.30, p = 0.0084). On multiple linear regression analysis, pre-pregnancy BMI and weight gain in pregnancy were positive independent determinants of infant birth weight, while family history of diabetes emerged as a negative independent correlate. Logistic regression analysis confirmed that pre-pregnancy BMI was a positive predictor of LGA (odds ratio (OR) = 1.25, 95% confidence interval (CI) 1.05-1.49), whereas family history of diabetes was again identified as a negative determinant (OR = 0.10, 95% CI 0.02-0.59). In contrast, neither measures of glycemia nor insulin resistance/sensitivity were independently associated with birth weight or LGA. CONCLUSION: In pregnant women with an abnormal GCT but without GDM, pre-gravid maternal obesity predicts increased infant birth weight, whereas family history of diabetes is independently associated with decreased infant size.

Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans.

CONTEXT: Hypoadiponectinemia has emerged as an independent risk factor for type 2 diabetes and cardiovascular disease. Although associations of adiponectin with central obesity and insulin resistance have been reported, very little data are available from studies using detailed measures of insulin sensitivity (S(I)) and/or body fat distribution in ethnic groups at high risk for metabolic disease. OBJECTIVE: The aim of the study was to identify the correlates of adiponectin in 1636 nondiabetic Hispanics and African-Americans. DESIGN: A cross-sectional analysis of participants in the Insulin Resistance Atherosclerosis Family Study was conducted. S(I) was determined from frequently sampled iv glucose tolerance tests with minimal model analysis. Subcutaneous and visceral adipose tissues (SAT, VAT, respectively) were determined with computed tomography. Triglyceride, high-density lipoprotein, C-reactive protein, and adiponectin were measured in fasting samples. Generalized estimating equation (GEE) models were used to identify factors associated with adiponectin concentration. SETTING: A multicenter study using a family-based design was conducted. PARTICIPANTS: A total of 1636 nondiabetic Hispanic and African-American subjects participated. MAIN OUTCOME MEASURES: Circulating adiponectin concentration was measured. RESULTS: Age, female gender, high-density lipoprotein, SAT, and S(I) were positive independent correlates of adiponectin, whereas glucose, CRP, and VAT were negative independent correlates (all P < 0.05). Ethnicity was not an independent correlate of adiponectin in this model (P = 0.27); however, an ethnicity by VAT interaction term was retained, indicating a stronger negative association of VAT with adiponectin in African-Americans compared with Hispanics. CONCLUSION: Directly measured S(I), VAT, and SAT were independently correlated with adiponectin in Hispanic and African-American subjects. The inverse association of VAT with adiponectin was stronger in African-Americans compared with Hispanics, a finding that suggests possible ethnic differences in the effects of visceral obesity.

Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample.

BACKGROUND: Common polymorphisms in the promoter of the APOC3 gene have been associated with hypertriglyceridemia and may impact on phenotypic expression of the metabolic syndrome (MetS). The rs7566605 marker, located near the INSIG2 gene, has been found to be associated with obesity, making it also a potential genetic determinant for MetS. The objective of this study is to examine the APOC3 -455T>C and the INSIG2 rs7566605 polymorphisms as potential genetic determinants for MetS in a multi-ethnic sample. METHODS: Subjects were genotyped for both the APOC3 -455T>C and INSIG2 rs7566605 polymorphisms, and classified for the presence or absence of MetS (NCEP ATP III and IDF definitions). The total study population included 2675 subjects (> or =18 years of age) from six different geographical ancestries. RESULTS: For the overall study population, the prevalence of MetS was 22.6% (NCEP ATP III definition). Carriers of > or =1 copy of APOC3 -455C were more likely to have MetS (NCEP ATP III definition) than noncarriers (carrier odds ratio 1.73, 95% CI 1.40 to 2.14, adjusting for age and study group). The basis of the association was related not only to a higher proportion of -455C carriers meeting the triglyceride and high-density lipoprotein cholesterol criteria, but also the blood pressure criteria compared with wild-type homozygotes. Plasma apo C-III concentrations were not associated with APOC3 -455T>C genotype. The INSIG2 rs7566605 polymorphism was not associated with MetS or measures of obesity. CONCLUSION: Meta-analysis of the sample of multiple geographic ancestries indicated that the functional -455T>C promoter polymorphism in APOC3 was associated with an approximately 2-fold increased risk of MetS, whereas the INSIG2 rs7566605 polymorphism was not associated with MetS.

Peroxisome proliferator-activated receptor gamma polymorphism Pro12Ala is associated with nephropathy in type 2 diabetes.

AIM: One putative determinant of diabetic nephropathy is the Pro12Ala (P12A) polymorphism in the gene encoding peroxisome proliferator-activated receptor gamma (PPARgamma). Previous research has found a "protective" role for the A12 allele in association with type 2 diabetes, atherosclerosis, and measures of kidney damage. The objective of this study was to investigate a possible role for the P12A PPARgamma gene polymorphism with diabetic nephropathy in an isolated aboriginal Canadian population at high risk for renal disease. METHODS: The P12A PPARgamma gene polymorphism was genotyped in 159 subjects (62 men and 97 women) of Oji-Cree descent. Participants were selected from a communitywide survey, which included diabetic nephropathy assessment by albumin/creatinine (A/C) ratio measurement. Genetic associations were tested by multivariate regression analysis, using a forward stepwise modeling approach. RESULTS: PPARgamma A12 allele carriers had reduced prevalence of microalbuminuria with a approximately 1.5-fold reduction in A/C ratio. Both PPARG P12A genotype [odds ratio (OR)=0.25, 95% confidence interval (95% CI)=0.076-0.85, P=.026] and systolic blood pressure (OR=1.69, 95% CI=1.15-2.48, P=.0075) were associated with microalbuminuria. CONCLUSIONS: The genetic influence of PPARG P12A genotype is modest and is overshadowed by duration of diabetes and systolic blood pressure as the major risk factors for diabetic nephropathy in the Oji-Cree population. The observed genetic association with diabetic nephropathy, however, confirms earlier findings, highlighting the importance of this polymorphism.