This study examined body-mass index, glucose tolerance, blood pressure, and cholesterol levels in American Indian children without diabetes who were then followed to adulthood. Obesity, glucose ...intolerance, and hypertension in childhood were strongly associated with premature death from endogenous causes, whereas hypercholesterolemia was not.
In American Indian children without diabetes who were followed to adulthood, obesity, glucose intolerance, and hypertension in childhood were strongly associated with premature death from endogenous causes, whereas hypercholesterolemia was not.
Despite recent increases in life expectancy, the rising global prevalence of obesity may reverse this trend.
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The rising rates and increasingly early onset of other chronic diseases such as type 2 diabetes may also affect mortality rates.
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Cardiovascular risk factors are common in children.
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,
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Although early-onset diabetes has been shown to raise mortality rates,
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and the relation between cardiovascular risk factors during adulthood and early death is well defined,
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–
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little is known about the way in which cardiovascular risk factors that are present during childhood affect life span. Defining such relationships may help predict the long-term human and . . .
Long-term data validating glycated hemoglobin (HbA
) in assessing the risk of type 2 diabetes in children are limited. HbA
, fasting plasma glucose (FPG), and 2-h postload plasma glucose (2hPG) ...concentrations were measured in a longitudinal study of American Indians to determine their utility in predicting incident diabetes, all of which is thought to be type 2 in this population.
Incident diabetes (FPG ≥126 mg/dL 7.0 mmol/L, 2hPG ≥200 mg/dL 11.1 mmol/L, HbA
≥6.5% 8 mmol/mol, or clinical diagnosis) was determined in 2,095 children without diabetes ages 10-19 years monitored through age 39, and in 2,005 adults ages 20-39 monitored through age 59. Areas under the receiver operating characteristic (ROC) curve for HbA
, FPG, and 2hPG in predicting diabetes within 10 years were compared.
During long-term follow-up of children and adolescents who did not initially have diabetes, the incidence rate of subsequent diabetes was fourfold (in boys) as high and more than sevenfold (in girls) as high in those with HbA
≥5.7% as in those with HbA
≤5.3%-greater rate ratios than experienced by adults in the same HbA
categories. Analyses of ROCs revealed no significant differences between HbA
, FPG, and 2hPG in sensitivity and specificity for identifying children and adolescents who later developed diabetes.
HbA
is a useful predictor of diabetes risk in children and can be used to identify prediabetes in children with other type 2 diabetes risk factors with the same predictive value as FPG and 2hPG.
Epigenetic markers are potential biomarkers for diabetes and related complications. Using a prospective cohort from the Hong Kong Diabetes Register, we perform two independent epigenome-wide ...association studies to identify methylation markers associated with baseline estimated glomerular filtration rate (eGFR) and subsequent decline in kidney function (eGFR slope), respectively, in 1,271 type 2 diabetes subjects. Here we show 40 (30 previously unidentified) and eight (all previously unidentified) CpG sites individually reach epigenome-wide significance for baseline eGFR and eGFR slope, respectively. We also develop a multisite analysis method, which selects 64 and 37 CpG sites for baseline eGFR and eGFR slope, respectively. These models are validated in an independent cohort of Native Americans with type 2 diabetes. Our identified CpG sites are near genes enriched for functional roles in kidney diseases, and some show association with renal damage. This study highlights the potential of methylation markers in risk stratification of kidney disease among type 2 diabetes individuals.
Gut microbial composition is associated with metabolic risk and differs markedly between industrialized (IND) and non-industrialized (non-IND) populations.
Objective: To characterize the gut ...microbiome of American Indian (AI) children with overweight/obesity relative to IND and non-IND individuals (including ancient AI gut microbiomes) .
Methods: Stool samples were from 7-10-year-old AI children with overweight/obesity enrolled in a lifestyle intervention trial on diabetes risk factors (2019-21) . Metagenomic analysis was performed on 39 samples from 25 individuals and compared to samples from age-matched (5-12-year-old) non-AI children in IND (N=380) or non-IND (N=90) populations.
Results: Mean age was 8.4 years (SD 1.11) , 44% were male. Mean age-sex-adjusted BMI z-score was 2.12 (SD 0.45) . By principal coordinates analysis, AI samples clustered in an intermediate position between the IND and non-IND samples (Figure 1) . AI children shared microbes with non-IND children that are rare in IND populations but common in ancient AI individuals (Prevotella copri, Coprococcus catus) .
Conclusions: The gut microbiome in a subset of AI children is distinct from the non-AI American gut microbiome. Further, AI children may have "inherited" gut microbes from their AI ancestors, which may contribute to differences in their metabolism relative to non-AI children.
Disclosure
A.Kostic: None. R.L.Hanson: None. M.Sinha: None.
Funding
American Diabetes Association (1-17-INI-13) ; National Institutes of Health (P30DK036836)
There is a developing interest in how immune genes may function in other physiological roles, and how traditionally non-immune peptides may, in fact, be active in immune contexts. In the absence of ...infection, the induction of the immune response is costly, and there are well-characterized trade-offs between immune defense and fitness. The agents behind these fitness costs are less understood. Here we implicate antimicrobial peptides (AMPs) as particularly costly effectors of immunity using an evolutionary framework. We describe the independent loss of AMPs in multiple lineages of Diptera (true flies), tying these observations back to life history. We then focus on the intriguing case of the glycine-rich AMP,
, and find several instances of loss, pseudogenization, and segregating null alleles. We suggest that
may be a particularly toxic component of the Dipteran immune response lost in flies either with reduced pathogen pressure or other environmental factors. As
have recently been described to have neurological roles, these findings parallel a developing interest in AMPs as potentially harmful neuropeptides, and AMPs in other roles beyond immunity.
To examine the role of glycemic measures performed during childhood in predicting future diabetes-related nephropathy and retinopathy in a high-risk indigenous American cohort.
We studied ...associations between glycated hemoglobin (HbA1c) and 2-h plasma glucose (PG), measured during childhood (age 5 to <20 years) in a longitudinal observational study of diabetes and its complications (1965-2007), and future albuminuria (albumin creatinine ratio ACR ≥30 mg/g), severe albuminuria (ACR ≥300 mg/g), and retinopathy (at least one microaneurysm or hemorrhage or proliferative retinopathy on direct ophthalmoscopy). Areas under the receiver operating characteristic curve (AUCs) for childhood glycemic measures when predicting nephropathy and retinopathy were compared.
Higher baseline levels of HbA1c and 2-h PG significantly increased the risk of future severe albuminuria (HbA1c: hazard ratio HR 1.45 per %; 95% CI 1.02-2.05 and 2-h PG: HR 1.21 per mmol/L; 95% CI 1.16-1.27). When categorized by baseline HbA1c, children with prediabetes had a higher incidence of albuminuria (29.7 cases per 1,000 person-years PY), severe albuminuria (3.8 cases per 1,000 PY), and retinopathy (7.1 cases per 1,000 PY) than children with normal HbA1c levels (23.8, 2.4, and 1.7 cases per 1,000 PY, respectively); children with diabetes at baseline had the highest incidence of the three complications. No significant differences were observed between AUCs for models with HbA1c, 2-h PG, and fasting PG when predicting albuminuria, severe albuminuria, or retinopathy.
In this study, higher glycemia levels ascertained by HbA1c and 2-h PG during childhood were associated with future microvascular complications; this demonstrates the potential utility of screening tests performed in high-risk children in predicting long-term health outcomes.
The United States Preventive Services Task Force recently questioned the benefits of risk-based screening for prediabetes/T2D in asymptomatic children with overweight/obesity due to lack of long-term ...health outcomes data. We examined associations of HbA1c and 2-hour post-load plasma glucose (2-hr PG), obtained during childhood (5 - <18 years) in a longitudinal study in an American Indian community (1965-2007), with future albuminuria albumin creatinine ratio (ACR) ≥ 30 mg/g, severe albuminuria (ACR ≥ 300 mg/g), and retinopathy (at least one microaneurysm or hemorrhage or proliferative retinopathy on direct ophthalmoscopy). We compared the performance of childhood glycemic measures in predicting these complications using area under the ROC curve (AUC). In children without T2D at baseline, higher HbA1c (HR=3.09 per 1%, 95% CI: 1.17-8.22) and 2-hr PG (HR= 1.48 per 1 mmol/L, 95% CI: 1.31-1.67) significantly increased retinopathy risk. Children with T2D based on baseline HbA1c had the highest incidence of albuminuria, severe albuminuria, and retinopathy compared to those with prediabetes and normal HbA1c levels. AUCs for HbA1c, 2-hr PG, or FPG were not significantly different (Figure). Higher levels of glycemia in childhood associated with future microvascular complications demonstrating the utility of screening tests performed in high-risk children in predicting long-term health outcomes.
Disclosure
L.Vazquez: None. E.Vazquez arreola: None. R.L.Hanson: None. M.Sinha: None.
Funding
National Institute of Diabetes and Digestive and Kidney Diseases
Short telomere length (TL) has been found to be associated with obesity related traits. However, most studies were cross-sectional in nature and conducted in adult subjects only. We aimed at ...examining the temporal relationship between telomere length and adiposity levels, measured by BMI, in both adults and youth. Our samples were selected from a population-based prospective cohort study in Southwest Amerindians who are at high risk for metabolic disorders. We obtained TL measures at 2 time points >10 years apart for 805 individuals who had concomitant BMI measures, and designated these as baseline and follow-up (f/u) exams; 1/3 were male and 1/3 were aged <18 years at baseline The means (range) of TL (measured in SD units), age at baseline, BMI at baseline, and the f/u period were 4.8±1.0 (2.2-8.5) SD units, 24.6±10.3 (5-63) years, 31.7±7.9 (15-63) kg/m2, and 13.6±1.7 years (11-18.4 years), respectively. No significant sex difference was observed, and 48% of subjects had longer TL at f/u. TL at baseline in youth was 14% longer than that of adults on average (p<E-4). There was no association between BMI at baseline and change in TL at f/u (β=-0.0036±0.0048 SD unit/kg*m-2, p=0.45 in the entire sample, similar results observed in adults or youth only), adjusted for effects of age, sex, ancestry, assay batches and the length of f/u. Longer TL at baseline had a modest association with lower change in BMI at f/u in youth (β=-2.89±1.47 kg*m-2/SD unit, p=0.050) but not in adults (β=0.96±0.96, p=0.32). In conclusion, our findings suggest that TL may be a risk factor for obesity, especially in younger people, but not the other way around. A larger study is underway to provide more robust estimates.
Disclosure
W.Hsueh: None. J.Lin: None. R.L.Hanson: None.
Funding
National Institutes of Health
Type 2 diabetes is a common disease worldwide, but its prevalence varies widely by geographical region and by race/ethnicity. This review summarises differences in the frequencies of type 2 diabetes ...according to race, ethnicity, socioeconomic position, area of residence and environmental toxins. Type 2 diabetes susceptibility often begins early in life, starting with genetic susceptibility at conception and continuing in later life, via in utero, childhood and adult exposures. Early-life factors may lead to overt type 2 diabetes in childhood or in later life, supporting the concept of developmental origins of health and disease. The causes of the racial/ethnic differences in incidence of type 2 diabetes are not well understood. Specifically, the relative contributions of genetic and environmental factors to such differences are largely unknown. With a few exceptions in isolated populations, there is little evidence that differences in frequencies of known type 2 diabetes susceptibility genetic alleles account for racial/ethnic differences, although the search for genetic susceptibility has not been uniform among the world’s racial/ethnic groups. In the USA, race/ethnicity is associated with many other risk factors for type 2 diabetes, including being overweight/obese, diet and socioeconomic status. Some studies suggest that some of these factors may account for the race/ethnic differences in prevalence of type 2 diabetes, although there is inadequate research in this area. A better understanding of the impact of these factors on type 2 diabetes risk should lead to more effective prevention and treatment of this disease. This has not yet been achieved but should be a goal for future research.
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