Gregers Stig Andersen

Fat and fat-free mass at birth: air displacement plethysmography measurements on 350 Ethiopian newborns

LBW increases the risk of a number of noncommunicable diseases in adulthood. However, birth weight (BW) cannot describe variability in infant body composition (BC). Variability in fat mass (FM) and fat-free mass (FFM) at birth may be particularly important in low-income countries because they undergo nutritional transition. There is a need for data on birth BC and its predictors from low-income countries in transition. We assessed absolute FM and FFM at birth and examined the role of gender, parity, GA, and LBW as predictors of birth BC. FM and FFM were assessed within 48 h of birth on 350 Ethiopian newborns using air displacement plethysmography (ADP). Female gender and being an infant of primi- or secundiparous mothers predicted lower BW and lower birth FFM but not FM, compared with male gender and infants of multiparous mothers, respectively. There was a positive linear relationship between BW and relative amount of FM for boys and girls. This study presents reference data on birth FM and FFM from a low-income setting and provides background for further longitudinal mapping of the relationship between fetal BC, childhood growth, and adult disease.

A philosophical analysis of the Hill criteria

The epidemiological literature contains an ongoing and diversified discussion of the Hill criteria. This article offers a philosophical analysis of the criteria, showing that the criteria are related to two different views of causality. The authors argue that the criteria of strength, specificity, consistency, experiment, and biological gradient are related to a probabilistic regularity view of causality, whereas the criteria of coherence, plausibility, and analogy are related to a generative view of causality. The criterion of temporality is not related to either view, but may in contrast be central in inferring direction from cause to effect. The authors illuminate the aim and limitations of the various criteria that need to be included when discussing them.

Prediction of First Cardiovascular Disease Event in Type 1 Diabetes Mellitus: The Steno Type 1 Risk Engine.

Background— Patients with type 1 diabetes mellitus are at increased risk of developing cardiovascular disease (CVD), but they are currently undertreated. There are no risk scores used on a regular basis in clinical practice for assessing the risk of CVD in type 1 diabetes mellitus. Methods and Results— From 4306 clinically diagnosed adult patients with type 1 diabetes mellitus, we developed a prediction model for estimating the risk of first fatal or nonfatal CVD event (ischemic heart disease, ischemic stroke, heart failure, and peripheral artery disease). Detailed clinical data including lifestyle factors were linked to event data from validated national registers. The risk prediction model was developed by using a 2-stage approach. First, a nonparametric, data-driven approach was used to identify potentially informative risk factors and interactions (random forest and survival tree analysis). Second, based on results from the first step, Poisson regression analysis was used to derive the final model. The final CVD prediction model was externally validated in a different population of 2119 patients with type 1 diabetes mellitus. During a median follow-up of 6.8 years (interquartile range, 2.9–10.9) a total of 793 (18.4%) patients developed CVD. The final prediction model included age, sex, diabetes duration, systolic blood pressure, low-density lipoprotein cholesterol, hemoglobin A1c, albuminuria, glomerular filtration rate, smoking, and exercise. Discrimination was excellent for a 5-year CVD event with a C-statistic of 0.826 (95% confidence interval, 0.807–0.845) in the derivation data and a C-statistic of 0.803 (95% confidence interval, 0.767–0.839) in the validation data. The Hosmer-Lemeshow test showed good calibration (P>0.05) in both cohorts. Conclusions— This high-performing CVD risk model allows for the implementation of decision rules in a clinical setting.

Incidence of Ketoacidosis in the Danish Type 2 Diabetes Population Before and After Introduction of Sodium–Glucose Cotransporter 2 Inhibitors—A Nationwide, Retrospective Cohort Study, 1995–2014

The U.S. Food and Drug Administration warns that sodium–glucose cotransporter 2 (SGLT2) inhibitors may lead to diabetic ketoacidosis (DKA). To establish a baseline occurrence of DKA in type 2 diabetes, we used national registries in Denmark to estimate incidence rates of DKA and linked the data to information on filled prescriptions to determine treatment exposure, with special attention paid to SGLT2 inhibitor use. Patients with filled prescription(s) for antidiabetes medication or a type 2 diabetes diagnosis identified through national registers (1995–2014) (1,2) were included. Patients were followed from the date of diagnosis until an event or censoring due to death or emigration, or by end of study 31 December 2014, whichever occurred first. Events of DKA were defined as a primary or secondary diagnosis in the National Patient Register between 1 January 1995 and 31 December 2014. Patients diagnosed with type 1 diabetes or who had a filled …

Abdominal Fat Distribution and Cardiovascular Risk in Men and Women With Different Levels of Glucose Tolerance

CONTEXT Regional fat distribution rather than overall obesity has been recognized as important to understanding the link between obesity and cardiovascular disease. OBJECTIVE We examined the associations of abdominal visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiovascular risk factors in a Caucasian population of men and women with normal glucose tolerance, prediabetes, or screen-detected diabetes. DESIGN, SETTING, AND PARTICIPANTS The study was based on cross-sectional analysis of data from 1412 adults age 45-80 years. VAT and SAT were assessed by ultrasound. The associations of VAT and SAT with blood pressure and lipids were examined by linear regression analysis adjusted for age, sex, smoking, alcohol, physical activity, glucose tolerance status (GTS), medication use, and body mass index. Effect modification by GTS and sex was examined, and stratified analyses performed. RESULTS Independent of SAT and overall obesity, VAT was associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels in both men and women and additionally associated with higher total cholesterol in men. SAT was independently associated with higher total cholesterol and low-density lipoprotein cholesterol levels in both sexes, and SAT was additionally associated with higher triglyceride and lower HDL cholesterol levels in women and with higher blood pressure in participants with diabetes. CONCLUSION Both abdominal VAT and SAT are independent of overall obesity associated with cardiovascular risk in a population of men and women at low to high risk of diabetes or with screen-detected diabetes.

Midupper arm circumference and weight-for-length z scores have different associations with body composition: evidence from a cohort of Ethiopian infants

BACKGROUND A midupper arm circumference (MUAC) <115 mm and weight-for-height z score (WHZ) or weight-for-length z score (WLZ) less than -3, all of which are recommended to identify severe wasting in children, often identify different children. The reasons behind this poor agreement are not well understood. OBJECTIVE We investigated the association between these 2 anthropometric indexes and body composition to help understand why they identify different children as wasted. DESIGN We analyzed weight, length, MUAC, fat-mass (FM), and fat-free mass (FFM) data from 2470 measurements from 595 healthy Ethiopian infants obtained at birth and at 1.5, 2.5, 3.5, 4.5, and 6 mo of age. We derived WLZs by using 2006 WHO growth standards. We derived length-adjusted FM and FFM values as unexplained residuals after regressing each FM and FFM against length. We used a correlation analysis to assess associations between length, FFM, and FM (adjusted and nonadjusted for length) and the MUAC and WLZ and a multivariable regression analysis to assess the independent variability of length and length-adjusted FM and FFM with either the MUAC or the WLZ as the outcome. RESULTS At all ages, length showed consistently strong positive correlations with the MUAC but not with the WLZ. Adjustment for length reduced observed correlation coefficients of FM and FFM with the MUAC but increased those for the WLZ. At all ages, both length-adjusted FM and FFM showed an independent association with the WLZ and MUAC with higher regression coefficients for the WLZ. Conversely, length showed greater regression coefficients for the MUAC. At all ages, the MUAC was shown to be more influenced than was the WLZ by the FM variability relative to the FFM variability. CONCLUSIONS The MUAC and WLZ have different associations with body composition, and length influences these associations differently. Our results suggest that the WLZ is a good marker of tissue masses independent of length. The MUAC acts more as a composite index of poor growth indexing jointly tissue masses and length. This trial was registered at www.controlled-trials.com as ISRCTN46718296.

Level and intensity of objectively assessed physical activity among pregnant women from urban Ethiopia

BackgroundWomen in low-income countries are generally considered to have a high physical workload which is sustained during pregnancy. Although most previous studies have been based on questionnaires a recent meta-analysis of doubly labeled water data has raised questions about the actual amount of physical activity performed. In this study we report objectively assessed levels of physical activity, cardiorespiratory fitness and muscular fitness among pregnant urban Ethiopian women, and their association with demographic characteristics and anthropometric measures.MethodsPhysical activity was measured for seven consecutive days in 304 women using a combined uniaxial accelerometer and heart rate sensor. Activity energy expenditure was determined using a group calibration in a branched equation model framework. Type and duration of activities were reported using a 24-hour physical activity recall and grip strength was assessed using a dynamometer.ResultsMedian (interquartile-range, IQR) activity energy expenditure was 31.1 (23.7-42.0) kJ/kg/day corresponding to a median (IQR) physical activity level of 1.46 (1.39-1.58). Median (IQR) time in sedentary, light, and moderate-to-vigorous intensity was 1100 (999–1175), 303 (223–374) and 40 (22–69) min/day, respectively. Mean (standard deviation) sleeping heart rate was 73.6 (8.0) beats/min and grip strength was 21.6 (4.5) kg. Activity energy expenditure was 14% higher for every 10 cm2 difference in arm muscle area and 10% lower for every 10 cm2 difference in arm fat area and 10-week difference in gestational age.ConclusionThe level and intensity of physical activity among pregnant women from urban Ethiopia is low compared to non-pregnant women from other low income countries as well as pregnant European women from high-income countries.

Calibration of bioelectrical impedance analysis for body composition assessment in Ethiopian infants using air-displacement plethysmography

Background/Objectives:Assessment of infant body composition (BC) is crucial to understand the consequences of suboptimal nutritional status and postnatal growth, and the effects of public health interventions. Bioelectrical impedance analysis (BIA) is a feasible, relatively inexpensive and noninvasive method for assessing BC. However, very little research has been conducted in low- and middle-income populations, where efforts to prevent or treat malnutrition in early life are a public health priority. We aimed to develop equations for predicting fat-free mass (FFM) and fat mass (FM) based on BIA in 0- to 6-month-old Ethiopian infants.Subjects/Methods:The study comprised a total of 186 BC assessments performed in 101 healthy infants, delivered at Jimma University Specialized Hospital. Infant air-displacement plethysmography (IADP) was the criterion method, whereas weight, length, sex, age and an impedance index (L2/Z50) were predictors. Prediction equations were developed using stepwise multiple linear regression and the accuracy was evaluated with a 10-fold cross-validation approach.Results:A linear regression model based on body weight, age and sex predicted FFM, estimated by IADP, with an adjusted R2 and root mean square error (RMSE) of 0.94 and 200 g, respectively. Adding impedance index to the model resulted in a significantly improved model fit (R2=0.95; RMSE=181 g). For infants below 3 months of age, inclusion of impedance index did not contribute to an improved model fit for predicting FFM compared with a model already comprising weight, sex and age.Conclusions:The derived equations predicted FFM with acceptable accuracy and may be used in future field surveys, epidemiological studies and clinical trials conducted in similar sub-Saharan African population groups aged 0–6 months.

Diabetes among migrants in Denmark: Incidence, mortality, and prevalence based on a longitudinal register study of the entire Danish population

OBJECTIVE Studies of diabetes in migrant populations have shown a higher prevalence compared to their respective countries of origin and to people natively born in the host country, but there is little population-based data on diabetes incidence and mortality in migrant populations. The aim of the current study was (1) to describe the incidence rates and prevalence of diabetes among first generation migrants in Denmark compared to the Danish background population, and (2) to compare standardised mortality rates (SMRs) for individuals with and without diabetes according to country of origin. RESEARCH DESIGN AND METHODS Information was obtained from linkage of the National Diabetes Register with mortality statistics and information from the Central Personal Register on country of origin. Age- and sex-specific estimates of prevalence, incidence rates, mortality rates and SMRs relative to the part of the population without diabetes were calculated based on follow up of the entire Danish population. RESULTS Compared with native born Danes, the incidence of diabetes was about 2.5 times higher among migrants from Africa, Asia, and the Middle East, and these migrant groups also showed significantly higher prevalence. The standardised mortality rates (SMR) were higher particularly above 50years of age among most migrant groups compared with native born Danes, and with a higher annual increase. CONCLUSIONS The highest diabetes incidence rates and prevalence estimates were observed among migrants from Africa, Asia, and the Middle East, and the annual increase in SMRs was higher in these groups compared to native born Danes.

The DEXLIFE study methods: Identifying novel candidate biomarkers that predict progression to type 2 diabetes in high risk individuals §

The incidence of type 2 diabetes (T2D) is rapidly increasing worldwide and T2D is likely to affect 592 million people in 2035 if the current rate of progression is continued. Today, patients are diagnosed with T2D based on elevated blood glucose, either directly or indirectly (HbA1c). However, the information on disease progression is limited. Therefore, there is a need to identify novel early markers of glucose intolerance that reflect the underlying biology and the overall physiological, metabolic and clinical characteristics of progression towards diabetes. In the DEXLIFE study, several clinical cohorts provide the basis for a series of clinical, physiological and mechanistic investigations in combination with a range of--omic technologies to construct a detailed metabolic profile of high-risk individuals across multiple cohorts. In addition, an exercise and dietary intervention study is conducted, that will assess the impact on both plasma biomarkers and specific functional tissue-based markers. The DEXLIFE study will provide novel diagnostic and predictive biomarkers which may not only effectively detect the progression towards diabetes in high risk individuals but also predict responsiveness to lifestyle interventions known to be effective in the prevention of diabetes.