OBJECTIVE In the Italian Diabetes and Exercise Study_2 (IDES_2), behavioral counseling promoted a sustained increase in physical activity (PA) volume (+3.3 MET h ⋅ week⁻¹), moderate- to vigorous-intensity PA (MVPA) (+6.4 min ⋅ day⁻¹), and light-intensity PA (LPA) (+0.8 h ⋅ day⁻¹) and decrease in sedentary time (SED-time) (−0.8 h ⋅ day⁻¹). Here, we investigated the relationships of changes in PA/SED-time with changes in physical fitness and cardiometabolic risk profile in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In this 3-year randomized clinical trial, 300 physically inactive and sedentary patients were randomized 1:1 to receive 1-month theoretical and practical counseling once a year or standard care. Changes in physical fitness and cardiovascular risk factors/scores according to quartiles of accelerometer-measured changes in PA/SED-time were assessed, together with univariate and multivariable associations between these parameters, in the whole cohort and by study arm. RESULTS Physical fitness increased and HbA_1c and coronary heart disease 10-year risk scores decreased with quartiles of MVPA and SED-time change. In quartile IV of MVPA increase and SED-time decrease, cardiorespiratory fitness increased by 5.23 and 4.49 mL ⋅ min⁻¹ ⋅ kg⁻¹ and HbA_1c decreased by 0.73 and 0.85%, respectively. Univariate correlations confirmed these relationships, and mean changes in both MPVA and SED-time predicted changes in physical fitness and cardiovascular risk factors/scores independently of one another and of other confounders. Similar findings were observed with LPA and PA volume and in each group separately. CONCLUSIONS Even modest increments in MVPA may have a clinically meaningful impact, and reallocating SED-time to LPA may also contribute to improved outcomes, possibly by increasing total energy expenditure.

OBJECTIVE Studies have shown a disparate association between body composition and the risk of type 2 diabetes. We assessed whether associations between differences in body composition and type 2 diabetes vary among ethnic groups with disparate cardiometabolic risk. RESEARCH DESIGN AND METHODS We used data from the Healthy Life in an Urban Setting (HELIUS) study, including individuals aged 18–70 years of African Surinamese (n = 3,997), South Asian Surinamese (n = 2,956), Turkish (n = 3,546), Moroccan (n = 3,850), Ghanaian (n = 2,271), and Dutch (n = 4,452) origin living in Amsterdam. Type 2 diabetes was defined using the World Health Organization criteria. Logistic regression was used to assess the relation between body composition and type 2 diabetes. Waist-to-hip ratio (WHR), waist circumference, BMI, and body fat percentage by bioelectrical impedance were used to estimate body composition. RESULTS Per unit change in BMI, only Ghanaian (odds ratio [OR] 0.94 [95% CI 0.89–0.99]) and Moroccan (0.94 [0.89–0.99]) women had a smaller increase in type 2 diabetes compared with the Dutch population, whereas the ORs for body fat percentage were 0.94 (0.89–1.00) for Ghanaian, 0.93 (0.88–0.99) for Moroccan, and 0.95 (0.90–1.00) for South Asian Surinamese women. There was no interaction between WHR and ethnicity on the risk of type 2 diabetes, and there were no differences in men. WHR had the highest precision in predicting type 2 diabetes in both men (C statistic = 0.78) and women (C statistic = 0.81). CONCLUSIONS The association between differences in body composition and type 2 diabetes is roughly the same in all ethnic groups. WHR seems the most reliable and consistent predictor of type 2 diabetes regardless of ethnic background.

OBJECTIVE Increasing evidence suggests that time spent sedentary predicts increasing cardiometabolic risk independent of other physical activity. We objectively measured activity levels in active older adults and examined the association between sedentary behavior and the continuous metabolic syndrome risk score (cMSy). RESEARCH DESIGN AND METHODS Older adults (age ≥65 years) were recruited from the Whistler Masters ski team, a group of active older adults who undergo organized group training. Daily activity levels were recorded with accelerometers (SenseWear) worn for 7 days. A compositional approach was used to determine proportion of the time spent sedentary as compared with all other nonsedentary behaviors (isometric log-ratio transformation for time spent sedentary [ILR1]). Waist circumference, triglycerides, HDL, systolic blood pressure, and fasting glucose were measured, and cMSy was calculated using principal component analysis (sum of eigenvalues ≥1.0). RESULTS Fifty-four subjects (30 women and 24 men, mean ± SE age 71.4 ± 0.6 years) were recruited. Subjects demonstrated high levels of physical activity (2.6 ± 0.2 h light activity and 3.9 ± 0.2 h moderate/vigorous activity). In our final parsimonious model, ILR1 showed a significant positive association with increasing cMSy (standardized β = 0.368 ± 0.110, R² = 0.40, P = 0.002), independent of age and biological sex. CONCLUSIONS Despite high levels of activity, ILR1 demonstrated a strong association with cMSy. This suggests that even in active older adults, sedentary behavior is associated with increasing cardiometabolic risk.

OBJECTIVE We investigated the cumulative burden and linear rates of change of major metabolic risk factors (MRFs) among Iranian adults in whom type 2 diabetes did and did not develop. RESEARCH DESIGN AND METHODS We included 7,163 participants (3,069 men) aged 20–70 years at baseline with at least three examinations during 1999–2018. Individual growth curve modeling was used for data analysis. Statistical interactions for sex by diabetes status were adjusted for age, family history of diabetes, smoking status, and physical activity level. RESULTS Study sample included 743 (316 men) new case subjects with diabetes. In both men and women, compared with individuals in whom diabetes did not develop, individuals in whom diabetes developed had a higher burden of all MRFs and a greater rate of change in BMI, fasting plasma glucose (FPG), systolic blood pressure (SBP), and diastolic blood pressure; however, the differences in burden and rate of change between those who did and did not develop diabetes were greater in women than in men. During the transition to diabetes, women experienced more adverse change in BMI, FPG, triglyceride, and HDL cholesterol (HDL-C) (diabetes-sex interaction P values <0.05) and faster rates of change in BMI, FPG, HDL-C, and total cholesterol (interaction P values <0.01) and SBP (interaction P = 0.055) than men. CONCLUSIONS The greater exposure of women to and burden of MRFs before onset of diabetes may have implications for implementing sex-specific strategies in order to prevent or delay diabetes complications.

OBJECTIVE We aimed to determine the individual and combined associations of lifestyle and metabolic factors with new-onset diabetes and major cardiovascular events among a Chinese population aged ≥40 years. RESEARCH DESIGN AND METHODS Baseline lifestyle information, waist circumference, blood pressure, lipid profiles, and glycemic status were obtained in a nationwide, multicenter, prospective study of 170,240 participants. During the up to 5 years of follow-up, we detected 7,847 individuals with new-onset diabetes according to the American Diabetes Association 2010 criteria and 3,520 cardiovascular events, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. RESULTS On the basis of 36.13% (population-attributable fraction [PAF]) risk attributed to metabolic risk components collectively, physical inactivity (8.59%), sedentary behavior (6.35%), and unhealthy diet (4.47%) moderately contributed to incident diabetes. Physical inactivity (13.34%), unhealthy diet (8.70%), and current smoking (3.38%) significantly contributed to the risk of major cardiovascular events, on the basis of 37.42% PAF attributed to a cluster of metabolic risk factors. Significant associations of lifestyle health status with diabetes and cardiovascular events were found across all metabolic health categories. Risks of new-onset diabetes and major cardiovascular events increased simultaneously according to the worsening of lifestyle and metabolic health status. CONCLUSIONS We showed robust effects of lifestyle status on new-onset diabetes and major cardiovascular events regardless of metabolic status and a graded increment of risk according to the combination of lifestyle and metabolic health, highlighting the importance of lifestyle modification regardless of the present metabolic status.

OBJECTIVE We examined young adults with and young adults without diabetes by using demographic data and cardiometabolic risk profiles and compared the risk profiles of younger versus older (aged ≥45 years) adults with diabetes. RESEARCH DESIGN AND METHODS Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2007–2016. Diabetes was defined by self-report of health care provider diagnosis or by A1C levels of 6.5% or higher among those without a self-reported diagnosis. The cardiometabolic risk profile included adiposity, blood pressure, serum lipids, healthy eating, physical activity (PA), and exposure to tobacco smoke. Adjusted difference in difference was calculated as the difference among younger adults with and younger adults without diabetes minus the difference among older adults with and older adults without diabetes. RESULTS Adults with diabetes in both age-groups had higher levels of adiposity, hypertension, and cholesterol and lower levels of healthy eating and leisure-time PA. However, the differences in high cholesterol and adiposity by diabetes status were greater among young adults compared with older adults after adjustment for demographics and health insurance status. Elevated lipids were 9.6 percentage points higher (95% CI 4.6, 14.5) and obesity was 37.3 percentage points higher (95% CI 31.8, 42.7) among young adults with diabetes compared with those without diabetes than among older adults with diabetes compared with those without diabetes. CONCLUSIONS Young adults with diabetes have high rates of cardiometabolic risk factors, which can lead to an increased disease prevalence and mortality rate among these individuals as they age.

OBJECTIVE Intrauterine exposure to maternal type 1 diabetes is associated with a less favorable metabolic profile later in life. Nonalcoholic fatty liver disease is the hepatic manifestation of a cluster of metabolic abnormalities linked to insulin resistance. This study aimed to evaluate the effect of maternal pregestational type 1 diabetes on the presence of fatty liver in offspring and the association between maternal BMI, glycemic control during pregnancy, offspring metabolic risk factors, and offspring level of soluble CD163 (sCD163) (a marker of macrophage activation) and risk of fatty liver. RESEARCH DESIGN AND METHODS This study was a prospective nationwide follow-up study of offspring (n = 278) of mothers with pregestational type 1 diabetes between 1993 and 1999 and matched control subjects (n = 303). Mean age at the time of follow-up was 16.7 years (range 13.0–20.4 years). We used the fatty liver index (FLI) and waist-to-height ratio (WHtR) to evaluate the presence of fatty liver among the offspring. An FLI ≥60 or WHtR >0.469 were used as cutoff points for fatty liver. RESULTS More type 1 diabetes–exposed offspring had high FLI and WHtR indices compared with unexposed control subjects. We found significant associations between increasing maternal prepregnancy BMI, being born large for gestational age, offspring level of sCD163, as well as offspring metabolic risk factors (decreasing adiponectin and HDL cholesterol and increasing leptin, HOMA of insulin resistance, and HOMA of insulin secretion) and degree of fatty liver. CONCLUSIONS Intrauterine exposure to maternal type 1 diabetes and higher maternal prepregnancy BMI may predispose to fatty liver in the offspring. Offspring metabolic risk factors, including sCD163 levels, are associated with indices of fatty liver.

OBJECTIVE The evidence for liquid meal replacements in diabetes has not been summarized. Our objective was to synthesize the evidence of the effect of liquid meal replacements on cardiometabolic risk factors in overweight/obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS Data sources included MEDLINE, EMBASE, and the Cochrane Library through 10 December 2018. We included randomized trials of ≥2 weeks assessing the effect of liquid meal replacements in weight loss diets compared with traditional weight loss diets on cardiometabolic risk factors in overweight/obese subjects with type 2 diabetes. Two independent reviewers extracted relevant data and assessed risk of bias. Data were pooled using the inverse variance method. The overall certainty of the evidence was evaluated using GRADE (Grading of Recommendations Assessment, Development and Evaluation). RESULTS Nine trial comparisons (N = 961 [median follow-up 24 weeks]) met eligibility criteria. Mean differences were for body weight −2.37 kg (95% CI −3.30 to −1.44), BMI −0.87 kg/m² (−1.31 to −0.42), body fat −1.66% (−2.17 to −1.15), waist circumference −2.24 cm (−3.72 to −0.77), HbA_1c −0.43% (−0.66 to −0.19) (−4.7 mmol/mol [−7.2 to −2.1]), fasting glucose −0.63 mmol/L (−0.99 to −0.27), fasting insulin −11.83 pmol/L (−23.11 to −0.54), systolic blood pressure −4.97mmHg (−7.32 to −2.62), and diastolic blood pressure −1.98 mmHg (−3.05 to −0.91). There was no effect on blood lipids. The overall certainty of the evidence was low to moderate owing to imprecision and/or inconsistency. CONCLUSIONS Liquid meal replacements in weight loss diets lead to modest reductions in body weight, BMI, and systolic blood pressure, and reductions of marginal clinical significance in body fat, waist circumference, HbA_1c, fasting glucose, fasting insulin, and diastolic blood pressure. More high-quality trials are needed to improve the certainty in our estimates.

OBJECTIVE The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated the beneficial effects of intensive therapy on atherosclerosis and clinical cardiovascular disease (CVD) outcomes. The current analyses evaluated the relationship between longitudinal changes in insulin dose and CVD risk factors and outcomes. RESEARCH DESIGN AND METHODS A total of 1,441 participants were randomly assigned to intensive or conventional diabetes therapy during the DCCT. After an average of 6.5 years of follow-up, 96% of the surviving cohort enrolled in the EDIC observational study, which included annual visits with detailed medical history, physical examination, and laboratory testing. CVD events were adjudicated by a review committee. Generalized linear mixed models and Cox proportional hazards regression models were used to assess the association between insulin dose and cardiometabolic risk factors and CVD risk, respectively, over a total of 30 years. RESULTS Higher insulin doses were significantly associated with a less favorable cardiometabolic risk profile (higher BMI, pulse rate, and triglycerides and lower HDL cholesterol) with the exception of lower diastolic blood pressure and lower LDL cholesterol. In a minimally adjusted model, a 0.1 unit/kg body wt/day increase in insulin dose was associated with a 6% increased risk of any CVD (95% CI 3, 9). However, the association with insulin dose was no longer significant after adjustment for other CVD risk factors. CONCLUSIONS During DCCT/EDIC, higher insulin doses were associated with adverse trends in several cardiometabolic risk factors, even after multivariable adjustment, but not with incident CVD outcomes.

OBJECTIVE To examine the course of cardiovascular autonomic neuropathy (CAN) and related cardiometabolic risk factors in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS CAN and cardiometabolic risk factors were assessed in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) at 6-year (n = 777) and 13-year (n = 443) follow-up examinations. Cardiovascular autonomic reflex tests (CARTs)—that is, lying to standing, deep breathing, and the Valsalva maneuver—and 2-min resting heart rate variability (HRV) indices were obtained as the main measures of CAN. Risk factors related to CAN status, as determined by CARTs, were studied by using multivariate logistic regressions. The effects of risk factors on continuous CARTs and HRV indices, and their changes over time, were estimated in linear mixed models. RESULTS A progressive yet heterogeneous course of CAN occurred between the 6- and 13-year follow-ups. Higher HbA_1c, weight, BMI, and triglycerides were associated with prevalent CAN. No significant effect of risk factors on CARTs was found when they were analyzed as continuous variables. CART indices decreased over time, and a trend of decreasing HRV indices was seen. Higher HbA_1c and BMI were associated with lower HRV index values, but these differences diminished over time. CONCLUSIONS These data confirm that hyperglycemia, obesity, and hypertriglyceridemia are negatively related to indices of CAN, although these effects diminish over time. The observed heterogeneous course of CAN may challenge the present clinical approach of categorically classifying CARTs to diagnose CAN and the notion of CAN being irreversible.

OBJECTIVE The aim of the present cross-sectional study was to examine the association among physical activity (PA), sedentary time (ST), and cardiometabolic risk in adults with prediabetes. RESEARCH DESIGN AND METHODS Participants (n = 2,326; 25–70 years old, 67% female) from eight countries, with a BMI >25 kg ⋅ m⁻² and impaired fasting glucose (5.6–6.9 mmol ⋅ L⁻¹) or impaired glucose tolerance (7.8–11.0 mmol ⋅ L⁻¹ at 2 h), participated. Seven-day accelerometry objectively assessed PA levels and ST. RESULTS Multiple linear regression revealed that moderate-to-vigorous PA (MVPA) was negatively associated with HOMA of insulin resistance (HOMA-IR) (standardized β = −0.078 [95% CI −0.128, −0.027]), waist circumference (WC) (β = −0.177 [−0.122, −0.134]), fasting insulin (β = −0.115 [−0.158, −0.072]), 2-h glucose (β = −0.069 [−0.112, −0.025]), triglycerides (β = −0.091 [−0.138, −0.044]), and CRP (β = −0.086 [−0.127, −0.045]). ST was positively associated with HOMA-IR (β = 0.175 [0.114, 0.236]), WC (β = 0.215 [0.026, 0.131]), fasting insulin (β = 0.155 [0.092, 0.219]), triglycerides (β = 0.106 [0.052, 0.16]), CRP (β = 0.106 [0.39, 0.172]), systolic blood pressure (BP) (β = 0.078 [0.026, 0.131]), and diastolic BP (β = 0.106 [0.39, −0.172]). Associations reported between total PA (counts ⋅ min⁻¹), and all risk factors were comparable or stronger than for MVPA: HOMA-IR (β = −0.151 [−0.194, −0.107]), WC (β = −0.179 [−0.224, −0.134]), fasting insulin (β = −0.139 [−0.183, −0.096]), 2-h glucose (β = −0.088 [−0.131, −0.045]), triglycerides (β = −0.117 [−0.162, −0.071]), and CRP (β = −0.104 [−0.146, −0.062]). CONCLUSIONS In adults with prediabetes, objectively measured PA and ST were associated with cardiometabolic risk markers. Total PA was at least as strongly associated with cardiometabolic risk markers as MVPA, which may imply that the accumulation of total PA over the day is as important as achieving the intensity of MVPA.

OBJECTIVE To investigate 1) differences in cardiometabolic risk and HOMA of insulin resistance (HOMA-IR) across BMI categories (underweight to morbid obesity), 2) whether fit children have lower cardiometabolic risk/HOMA-IR than unfit children in each BMI category, and 3) differences in cardiometabolic risk/HOMA-IR in normal-weight unfit children and obese fit children. RESEARCH DESIGN AND METHODS A pooled study including cross-sectional data from three projects (n = 1,247 children aged 8–11 years). Cardiometabolic risk was assessed using the sum of the sex- and age-specific z scores for triglycerides, HDL cholesterol, glucose, and the average of systolic and diastolic blood pressure and HOMA-IR. RESULTS A significant linear association was observed between the risk score and BMI categories (P trend ≤0.001), with every incremental rise in BMI category being associated with a 0.5 SD higher risk score (standardized β = 0.474, P < 0.001). A trend was found showing that as BMI categories rose, cardiorespiratory fitness (CRF) attenuated the risk score, with the biggest differences observed in the most obese children (−0.8 SD); however, this attenuation was significant only in mild obesity (−0.2 SD, P = 0.048). Normal-weight unfit children had a significantly lower risk score than obese fit children (P < 0.001); however, a significant reduction in the risk score was found in obese fit compared with unfit children (−0.4 SD, P = 0.027). Similar results were obtained for HOMA-IR. CONCLUSIONS As BMI categories rose so did cardiometabolic risk and HOMA-IR, which highlights the need for obesity prevention/treatment programs in childhood. Furthermore, CRF may play an important role in lowering the risk of cardiometabolic diseases in obese children.

OBJECTIVE Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA_1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.