Quoc Manh Nguyen

Changes in Risk Variables of Metabolic Syndrome Since Childhood in Pre-Diabetic and Type 2 Diabetic Subjects: The Bogalusa Heart Study

OBJECTIVE—That type 2 diabetes is associated with the metabolic syndrome is known. However, information is lacking regarding the long-term and adverse changes of metabolic syndrome variables in the development of type 2 diabetes from childhood to adulthood. RESEARCH DESIGN AND METHODS—Observations were examined, retrospectively, in a community-based cohort of normoglycemic (n = 1,838), pre-diabetic (n = 90), and type 2 diabetic (n = 60) subjects followed serially for cardiovascular risk factors during childhood (4–11 years), adolescence (12–18 years), and adulthood (19–44 years). RESULTS—Diabetic subjects versus normoglycemic subjects had significantly higher levels of subscapular skinfold, BMI, triglycerides, glucose, insulin, and homeostasis model assessment of insulin resistance and lower levels of HDL cholesterol beginning in childhood and higher levels of mean arterial pressure (MAP) in adolescence and adulthood. In a multivariate model including BMI, MAP, HDL cholesterol, LDL cholesterol, triglycerides, glucose, and insulin, adjusted for age, age2, race, sex, and race × sex interaction, adverse changes in glucose and LDL cholesterol were independently associated with pre-diabetic subjects, whereas adverse changes in BMI, glucose, and HDL cholesterol were associated with diabetic subjects. As young adults, pre-diabetic and diabetic groups displayed a significantly higher prevalence of obesity, hypertension, dyslipidemia, hyperinsulinemia, and metabolic syndrome. CONCLUSIONS—These findings indicate that adverse levels of risk variables of metabolic syndrome, adiposity, and measures of glucose homeostasis accelerating since childhood characterize the early natural history of type 2 diabetes and underscore the importance of early prevention and intervention on risk factors beginning in childhood.

A diagnosis of the metabolic syndrome in youth that resolves by adult life is associated with a normalization of high carotid intima-media thickness and type 2 diabetes mellitus risk: the Bogalusa heart and cardiovascular risk in young Finns studies.

OBJECTIVES The aim of this study was to examine the effect of resolution from metabolic syndrome (MetS) between youth and adulthood on carotid artery intima-media thickness (IMT) and type 2 diabetes mellitus (T2DM). BACKGROUND Published findings demonstrate that youth with MetS are at increased risk of cardio-metabolic outcomes in adulthood. It is not known whether this risk is attenuated in those who resolve their MetS status. METHODS Participants (n = 1,757) from 2 prospective cohort studies were examined as youth (when 9 to 18 years of age) and re-examined 14 to 27 years later. The presence of any 3 components (low high-density lipoprotein cholesterol, high triglycerides, high glucose, high blood pressure, or high body mass index) previously shown to predict adult outcomes defined youth MetS; the harmonized MetS criteria defined adulthood MetS. Participants were classified according to their MetS status at baseline and follow-up and examined for risk of high IMT and T2DM. RESULTS Those with MetS in youth and adulthood were at 3.4 times the risk (95% confidence interval: 2.4 to 4.9) of high IMT and 12.2 times the risk (95% confidence interval: 6.3 to 23.9) of T2DM in adulthood compared with those that did not have MetS at either time-point, whereas those that had resolved their youth MetS status by adulthood showed similar risk to those that did not have MetS at either time-point (p > 0.20 for all comparisons). CONCLUSIONS Although youth with MetS are at increased risk of adult high IMT and T2DM, these data indicate that the resolution of youth MetS by adulthood can go some way to normalize this risk to levels seen in those who have never had MetS.

Utility of childhood glucose homeostasis variables in predicting adult diabetes and related cardiometabolic risk factors: the Bogalusa Heart Study

OBJECTIVE This study examines the usefulness of childhood glucose homeostasis variables (glucose, insulin, and insulin resistance index [homeostasis model assessment of insulin resistance {HOMA-IR}]) in predicting pre-diabetes and type 2 diabetes and related cardiometabolic risk factors in adulthood. RESEARCH DESIGN AND METHODS This retrospective cohort study consisted of normoglycemic (n = 1,058), pre-diabetic (n = 37), and type 2 diabetic (n = 25) adults aged 19–39 years who were followed on average for 17 years since childhood. RESULTS At least 50% of the individuals who ranked highest (top quintile) in childhood for glucose homeostasis variables maintained their high rank by being above the 60th percentile in adulthood. In a multivariate model, the best predictors of adulthood glucose homeostasis variables were the change in BMI Z score from childhood to adulthood and childhood BMI Z score, followed by the corresponding childhood levels of glucose, insulin, and HOMA-IR. Further, children in the top decile versus the rest for insulin and HOMA-IR were 2.85 and 2.55 times, respectively, more likely to develop pre-diabetes; children in the top decile versus the rest for glucose, insulin, and HOMA-IR were 3.28, 5.54, and 5.84 times, respectively, more likely to develop diabetes, independent of change in BMI Z score, baseline BMI Z score, and total-to-HDL cholesterol ratio. In addition, children with adverse levels (top quintile versus the rest) of glucose homeostasis variables displayed significantly higher prevalences of, among others, hyperglycemia, hypertriglyceridemia, and metabolic syndrome. CONCLUSIONS Adverse levels of glucose homeostasis variables in childhood not only persist into adulthood but also predict adult pre-diabetes and type 2 diabetes and relate to cardiometabolic risk factors.

Fasting Plasma Glucose Levels Within the Normoglycemic Range in Childhood as a Predictor of Prediabetes and Type 2 Diabetes in Adulthood: The Bogalusa Heart Study

OBJECTIVES To determine whether childhood elevated fasting plasma glucose (FPG) levels within the normoglycemic range predict diabetes in adulthood. DESIGN Retrospective cohort study. SETTING Community of Bogalusa, Louisiana. PARTICIPANTS Normoglycemic (n = 1723), prediabetic (n = 79), and type 2 diabetic (n = 47) adults aged 19 to 44 years followed up serially for an average of 21 years since childhood. Main Exposures Association of elevated baseline childhood FPG levels with the prediabetic or diabetic status at the last survey in adulthood. MAIN OUTCOME MEASURES Receiver operating characteristic analysis and longitudinal logistic regression odds ratios. RESULTS The prevalent rate of adult diabetes status by quartiles of baseline childhood FPG levels showed an adverse trend for prediabetes (P < .001) and diabetes (P = .03), with an apparent threshold occurring at or above the 50th percentile (86 mg/dL). Regarding the predictive value of the above threshold, the area under the receiver operating curve analysis yielded a C value of 0.855 for prediabetes and 0.789 for diabetes models, with sensitivity and specificity, respectively, of 76.9% and 85.2% for prediabetes and 75.0% and 76.0% for diabetes. In a multivariate analysis that included anthropometric, hemodynamic, and metabolic variables from childhood to adulthood and baseline childhood FPG status (> or = vs < 50th percentile), individuals with elevated childhood FPG levels were 3.40 times more likely to develop prediabetes (P < .001) and 2.06 times more likely to develop diabetes (P = .05) as adults. CONCLUSION The fact that elevated FPG level in childhood, even within the normoglycemic range, is a predictor of type 2 diabetes in younger adulthood has implications for health care policy.

Elevated liver function enzymes are related to the development of prediabetes and type 2 diabetes in younger adults: the Bogalusa Heart Study.

OBJECTIVE Elevations in alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT), surrogate markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of metabolic syndrome and related type 2 diabetes. However, information is limited regarding the long-term predictability of ALT and GGT in the development of prediabetes and type 2 diabetes. RESEARCH DESIGN AND METHODS In this retrospective cohort study, normoglycemic (n = 874), prediabetic (n = 101), and diabetic (n = 80) adults aged 26–50 years (average age 41.3 years) were followed over an average period of 16 years since their young adulthood (aged 18–38 years, average age 25.1 years), with measurements of cardiometabolic risk factor variables including ALT and GGT. RESULTS The follow-up prevalence rate of adult diabetes status by quartiles of baseline ALT and GGT levels showed an adverse trend for both prediabetes (P < 0.05) and diabetes (P < 0.01). In a longitudinal multivariate logistic regression analysis that included anthropometric, hemodynamic, and metabolic variables, as well as alcohol consumption and smoking, individuals with elevated baseline ALT and GGT levels (per 1-SD increment) were 1.16 and 1.20 times, respectively, more likely to develop diabetes (P = 0.05 for ALT and P < 0.01 for GGT); no such associations were noted for prediabetes. Regarding the predictive value of ALT and GGT, the area under the receiver operating curve analysis yielded C values ranging from 0.70 to 0.82, with values significantly higher for diabetes compared with prediabetes. CONCLUSIONS These findings in younger adults suggest potential clinical utility of including ALT and GGT as biomarkers in diabetes risk assessment formulations.

Correlates of Age Onset of Type 2 Diabetes Among Relatively Young Black and White Adults in a Community: The Bogalusa Heart Study

OBJECTIVE The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults. RESEARCH DESIGN AND METHODS This prospective cohort study consisted of normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18–50 years who were followed for an average of 16 years. RESULTS The incidence rate of the onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for age-groups 18–29, 30–39, and 40–50 and total sample, respectively. Incidences of diabetes increased with age by race and sex groups (P for trend ≤0.01); higher in black females versus white females and blacks versus whites in total sample (P < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio [HR] 5.24) and plasma insulin were significantly associated with diabetes incidence at the youngest age (18–29 years); black race, BMI, and glucose at age 30–39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40–50 years; and black race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole cohort. Further, patients with diabetes, regardless of age onset, displayed a significantly higher prevalence of maternal history of diabetes at baseline (P < 0.01). CONCLUSIONS In relatively young adults, predictability of baseline cardiometabolic risk factors along with race, sex, and parental history of diabetes for the onset of type 2 diabetes varied by age-group. These findings have implications for early prevention and intervention in relatively young adults.

Glycemic status, metabolic syndrome, and cardiovascular risk in children.

The metabolic syndrome and adult manifestation of prediabetes and diabetes are major public health problems that begin in childhood. Prevention must be considered as a serious public health issue. Health education and health promotion of school children needs incorporation as a community effort.

Progression of segment-specific carotid artery intima-media thickness in young adults (from the Bogalusa Heart Study).

Carotid intima-media thickness (CIMT) progression is predictive of future cardiovascular events in middle-age and older adults. However, information is scant on segment-specific CIMT progression by race (black vs white) and gender and its predictors during short-term follow-up in asymptomatic young adults. B-mode ultrasound images of the far walls of both carotid arteries were obtained in 842 subjects aged 24 to 43 years and enrolled in the Bogalusa Heart Study (70% whites and 42% men). The CIMT and cardiometabolic risk variables were measured at baseline and after an average of 2.4 years. The mean CIMT progression rates/year adjusted for age, race, and gender were greatest at the bulb, followed by the internal and common carotid segments (p <0.0001). In a multivariate logistic model, age, mean arterial pressure, and high-density lipoprotein cholesterol were significantly associated with common CIMT progression. Smoking, age, insulin resistance index, and mean arterial pressure were significantly associated with bulb CIMT progression; and the waist/height ratio, smoking, age, and mean arterial pressure were significantly associated with internal CIMT progression, independent of the baseline CIMT and traditional cardiometabolic risk variables, including adiponectin, C-reactive protein, and intercellular adhesion molecules. In addition, the status of progression was associated with a greater prevalence of metabolic syndrome (common and internal CIMT, p <0.05; bulb CIMT, p <0.0001) and diabetes (bulb CIMT only, p <0.001). In conclusion, in younger adults, the magnitude of progression of CIMT within a short period varied in a segment-specific manner, regardless of race or gender, and was predictable using modifiable traditional risk factors. This could have implications for preventive and interventional cardiology.

Distribution and Cardiovascular Risk Correlates of Plasma Soluble Intercellular Adhesion Molecule-1 Levels in Asymptomatic Young Adults from a Biracial Community: The Bogalusa Heart Study

PURPOSE That circulating soluble form of intercellular adhesion molecule-1 (sICAM-1) is associated with an increased risk for coronary artery disease is well recognized. However, information is scant regarding the distribution and cardiovascular (CV) risk correlates of sICAM-1 in asymptomatic young adults. METHODS Plasma sICAM-1 was measured in 1,184 black and white persons in the Bogalusa Heart Study cohort (70% white, 43% male), aged 24 to 44 years. CV risk was assessed in terms of CV risk factors, status of parental CV disease, and composite carotid intima-media thickness (IMT). RESULTS sICAM-1 levels displayed race difference (whites > blacks, p<0.0001), but no sex difference. In multivariate analysis including age, race, sex, smoking status, waist circumference, mean arterial pressure, low- and high-density lipoprotein (LDL and HDL) cholesterols, triglycerides, insulin resistance index, C-reactive protein (CRP), and adiponectin, the significant predictors of sICAM-1, in order of entry, were race (white > black), smoking, CRP, and waist circumference. Furthermore, there was a smoking by waist circumference interaction in that smoking attenuated the magnitude of correlation between waist circumference and sICAM-1. Levels of sICAM-1 adjusted for age, race, sex, and smoking increased with number of metabolic syndrome components (p for trend<0.01); positive family history of CV disease (p<0.05); and increased in composite carotid IMT specific for age, race, and sex (p for trend<0.05). CONCLUSION These findings underscore the potential value of plasma sICAM-1 as an additional biomarker for CV risk among asymptomatic young adults.

Black–White Divergence Influencing Impaired Fasting Glucose and Type 2 Diabetes Mellitus

Impaired glucose homeostasis is one of the most common causes of death in the U.S. The progressive global epidemic of obesity makes it a major causal factor for pre-diabetes and type 2 diabetes, which may represent the two categories of impaired glucose regulation. Recognition of the importance of black–white contrast in the prevalence of type 2 diabetes mellitus has stirred up interest in its potential role in the development and progression of diabetes. Accumulating evidence suggests that multiple cardiometabolic risk factors such as insulin resistance/hyperinsulinemia, adiposity, genetic predisposition, low birth weight, prepuberty, inflammation markers including C-reactive protein and adiponectin, chronic kidney dysfunction, and environmental and socio-economic status lead to the black–white divergence in type 2 diabetes. Early prevention and intervention for these risk factors, especially obesity and altered lifestyles involving physical activity and dietary consumption, may help to neutralize the racial disparities seen in the emerging epidemic of diabetes beginning in youth.