Early-Adulthood Cardiovascular Disease Risk Factor Profiles Among Individuals With and Without Diabetes in the Framingham Heart Study

OBJECTIVE Many studies of diabetes have examined risk factors at the time of diabetes diagnosis instead of considering the lifetime burden of adverse risk factor levels. We examined the 30-year cardiovascular disease (CVD) risk factor burden that participants have up to the time of diabetes diagnosis. RESEARCH DESIGN AND METHODS Among participants free of CVD, incident diabetes cases (fasting plasma glucose ≥126 mg/dL or treatment) occurring at examinations 2 through 8 (1979–2008) of the Framingham Heart Study Offspring cohort were age- and sex-matched 1:2 to controls. CVD risk factors (hypertension, high LDL cholesterol, low HDL cholesterol, high triglycerides, obesity) were measured at the time of diabetes diagnosis and at time points 10, 20, and 30 years prior. Conditional logistic regression was used to compare risk factor levels at each time point between diabetes cases and controls. RESULTS We identified 525 participants with new-onset diabetes who were matched to 1,049 controls (mean age, 60 years; 40% women). Compared with those without diabetes, individuals who eventually developed diabetes had higher levels of hypertension (odds ratio [OR], 2.2; P = 0.003), high LDL (OR, 1.5; P = 0.04), low HDL (OR, 2.1; P = 0.0001), high triglycerides (OR, 1.7; P = 0.04), and obesity (OR, 3.3; P < 0.0001) at time points 30 years before diabetes diagnosis. After further adjustment for BMI, the ORs for hypertension (OR, 1.9; P = 0.02) and low HDL (OR, 1.7; P = 0.01) remained statistically significant. CONCLUSIONS CVD risk factors are increased up to 30 years before diagnosis of diabetes. These findings highlight the importance of a life course approach to CVD risk factor identification among individuals at risk for diabetes

Fasting and postchallenge glycemia and cardiovascular disease risk. The Framingham Offspring Study

WSTĘP. Celem pracy było zbadanie słuszności hipotezy, według której hiperglikemia na czczo (FHG, fasting hyperglycemia) i glikemia 2 godziny po obciążeniu glukozą (2hPG, 2-h postchallenge glycemia) niezależnie zwiększają ryzyko chorób sercowo-naczyniowych (CVD, cardiovascular disease). MATERIAŁ I METODY. W latach 1991-1995 autorzy przebadali 3370 uczestników badania Framingham Offspring Study, u których nie występowały objawy kliniczne CVD (choroba wieńcowa, udar mózgu lub chromanie przestankowe) ani cukrzyca, wymagająca leczenia farmakologicznego. Okres obserwacji pod kątem występowania CVD wynosił 4 lata. W celu oceny ryzyka związanego z FHG (stężenie glukozy na czczo ł 7,0 mmol/l) i 2hPG niezależnie od wpływu standardowych czynników ryzyka CVD, zastosowano model regresji proporcjonalnego ryzyka Coxa. WYNIKI. Średni wiek badanych wynosił 54 lata, 54% chorych stanowiły kobiety. Uprzednio nierozpoznaną cukrzycę stwierdzono u 3,2% na podstawie FHG, a u 4,9% (164 osoby), opierając się na wartościach FHG lub 2hPG ł 11,1 mmol/l. Spośród tych 164 chorych u 55 (33,5%) 2hPG było ł 11,1 mmol/ przy prawidłowym FHG, ale stanowiły one jedynie 1,7% z 3261 badanych bez FHG. W czasie 12 242 pacjentolat obserwacji wystąpiło 118 incydentów CVD. W oddzielnych modelach, skorygowanych względem płci i standardowych czynników ryzyka chorób sercowo-naczyniowych, ryzyko względne (RR, relative risk) CVD dla glikemii na czczo (FPG, fasting plasma glucose) większej lub równej 7,0 mmol/l wynosiło 2,8 (95% przedział ufności 1,6&#8211;5,0), a dla wzrostu 2hPG o 2,1 mmol/l - 1,2 (1,1&#8211;1,3). W modelu wspólnym RR dla FHG zmalało i wynosiło 1,5 (0,7&#8211;3,6), podczas gdy RR dla 2hPG pozostało istotnie podwyższone (1,1; 1,02&#8211;1,3). Analiza statystyczna c dla modelu obejmującego jedynie standardowe czynniki ryzyka CVD wyniosła 0,744; po dołączeniu FHG - 0,746, a po dodaniu FHG i 2hPG - 0,752. WNIOSKI. Glikemia po doustnym obciążeniu glukozą jest niezależnym czynnikiem ryzyka chorób sercowo-naczyniowych, ale wartość predykcyjna 2hPG jest niewielka w stosunku do standardowych czynników ryzyka CVD.INTRODUCTION. To test the hypothesis that fasting hyperglycemia (FHG) and 2-h postchallenge glycemia (2hPG) independently increase the risk for cardiovascular disease (CVD). MATERIAL AND METHODS. During 1991&#8211;1995, we examined 3,370 subjects from the Framingham Offspring Study who were free from clinical CVD (coronary heart disease, stroke, or intermittent claudication) or medication-treated diabetes, and we followed them for 4 years for incident CVD events. We used proportional-hazards regression to assess the risk associated with FHG (fasting plasma glucose &#8805; 7.0 mmol/l) and 2hPG, independent of the risk predicted by standard CVD risk factors. RESULTS. Mean subject age was 54 years, 54% were women, and previously undiagnosed diabetes was present in 3.2% by FHG and 4.9% (164) by FHG or a 2hPG &#8805; 11.1 mmol/l. Of these 164 subjects, 55 (33.5%) had 2hPG &#8805; 11.1 without FHG, but these 55 subjects represented only 1.7% of the 3,261 subjects without FHG. During 12,242 person-years of follow-up, there were 118 CVD events. In separate sex- and CVD risk-adjusted models, relative risk (RR) for CVD with fasting plasma glucose &#8805; 7.0 mmol/l was 2.8 (95% CI 1.6&#8211;5.0); RR for CVD per 2.1 mmol/l increase in 2hPG was 1.2 (1.1&#8211;1.3). When modeled together, the RR for FHG decreased to 1.5 (0.7&#8211;3.6), whereas the RR for 2hPG remained significant (1.1, 1.02&#8211;1.3). The c-statistic for a model including CVD risk factors alone was 0.744; with addition of FHG, it was 0.746, and with FHG and 2hPG, it was 0.752. CONCLUSIONS. Postchallenge hyperglycemia is an independent risk factor for CVD, but the marginal predictive value of 2hPG beyond knowledge of standard CVD risk factors is small

Trends in the Association of Parental History of Obesity over 60 Years

Objective: The association of familial as compared to genetic factors in the current obesogenic environment, compared to earlier, leaner time periods, is uncertain. Design and Methods Participants from the Framingham Heart Study were classified according to parental obesity status in the Original, Offspring, and Third Generation cohorts; mean BMI levels were estimated and we compared the association of parental history across generations. Finally, a genetic risk score comprised of 32 well-replicated single nucleotide polymorphisms for BMI was examined in association with BMI levels in 1948, 1971, and 2002. Results: BMI was 1.49 kg/m2 higher per each affected parent among the Offspring, and increased to 2.09 kg/m2 higher among the Third Generation participants (p-value for the cohort comparison=0.007). Parental history of obesity was associated with increased weight gain (p<0.0001) and incident obesity (p=0.009). Despite a stronger association of parental obesity with offspring BMI in more contemporary time periods, we observed no change in the effect size of a BMI genetic risk score from 1948 to 2002 (p=0.11 for test of trend across the time periods). Conclusions: The association of parental obesity has become stronger in more contemporary time period, whereas the association of a BMI genetic risk score has not changed

Comparing Two Waist-to-Height Ratio Measurements with Cardiometabolic Risk Factors among Youth with Diabetes

Background: Waist circumference (WC) is commonly measured by either the World Health Organization (WHO) or National Health and Nutrition Examination Survey (NHANES) protocol. Objective: Compare the associations of WHO vs. NHANES WC-to-height ratio (WHtR) protocols with cardiometabolic risk factors (CMRFs) in a sample of youth with diabetes. Methods: For youth (10–19 years old with type 1 [N=3082] or type 2 [N=533] diabetes) in the SEARCH for Diabetes in Youth Study, measurements were obtained of WC (by two protocols), weight, height, fasting lipids (total cholesterol, triglycerides, HDL cholesterol, Non-HDL cholesterol) and blood pressures. Associations of CMRFs with WHO and NHANES WHtR were modeled stratified by body mass index (BMI) percentiles for age/sex: lower BMI (&lt;85th BMI percentile; N=2071) vs. higher BMI (≥85th percentile; N=1594). Results: Among lower-BMI participants, both NHANES and WHO WHtR were associated (p&lt;0.005) with all CMRFs except blood pressure. Among higher-BMI participants, both NHANES and WHO WHtR were associated (p&lt;0.05) with all CMRFs. WHO WHtR was more strongly associated (p&lt;0.05) than NHANES WHtR with triglycerides, non-HDL cholesterol, and systolic blood pressure in lower-BMI participants. Among high-BMI participants, WHO WHtR was more strongly associated (p&lt;0.05) than NHANES WHtR with triglycerides and systolic blood pressure. Conclusion: Among youth with diabetes, WHtR calculated from either WC protocol captures cardiometabolic risk. The WHO WC protocol may be preferable to NHANES WC

Correlates of Medical Nutrition Therapy and Cardiovascular Outcomes in Youth With Type 1 Diabetes

To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) varies by socio-demographic characteristics and cardiovascular (CVD) risk factor

The influence of exposure to maternal diabetes in utero on the rate of decline in β-cell function among youth with diabetes

A relationship between exposure to maternal diabetes in utero and a younger age at diagnosis of type 2 diabetes was detected in SEARCH for Diabetes in Youth Study, while no significant association was detected with paternal diabetes status, suggesting an independent effect of the intrauterine exposure to hyperglycemia. We assessed the influence of exposure to maternal diabetes in utero on beta cell decline measured using fasting C-peptide (FCP) among 1079 youth with diabetes, including 941 with type 1 and 138 with type 2, who were followed post-diagnosis for an average of 58 months. No significant relationship was detected between exposure to maternal diabetes in utero and change in FCP levels in youth with type 1 or type 2 diabetes. These findings suggest that exposure to maternal diabetes in utero may not be an important determinant of short-term beta-cell function decline in youth with type 1 or type 2 diabetes

The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions

The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions