Background: The fast-growing literature suggests that the Chinese famine of 1959–1961 drives current and future type 2 diabetes (T2D) epidemics in China. This conclusion may be premature, as many Chinese famine studies have major methodological problems. We examine these problems, demonstrate how they bias the study results, and formulate recommendations to improve the quality of future studies. Methods: We searched English and Chinese databases for studies that examined the relationship between prenatal exposure to the Chinese famine and adult T2D from inception to 8 February 2022. We extracted information on T2D cases and study populations of individuals born during the famine (famine births), before the famine (prefamine births), and after the famine (postfamine births). We used random-effects models to compare the odds of T2D in famine births to several control groups, including postfamine births, combined pre- and postfamine births, and prefamine births. We used meta-regressions to examine the impacts of age differences between comparison groups on famine effect estimates and the role of other characteristics, including participant sex, age, and T2D assessments; famine intensity; residence; and publication language. Potential sources of heterogeneity and study quality were also evaluated. Results: Twenty-three studies met our inclusion criteria. The sample sizes ranged from less than 300 to more than 360,000 participants. All studies defined the famine exposure based on the participants’ dates of birth, and 18 studies compared famine births and postfamine births to estimate famine effects on T2D. The famine and postfamine births had an age difference of three years or more in all studies. The estimates of the famine effect varied by the selection of controls. Using postfamine births as controls, the OR for T2D among famine births was 1.50 (95% CI 1.34–1.68); using combined pre- and postfamine births as controls, the OR was 1.12 (95% CI 1.02–1.24); using prefamine births as controls, the OR was 0.89 (95% CI 0.79–1.00). The meta-regressions further showed that the famine effect estimates increased by over 1.05 times with each one-year increase in ignored age differences between famine births and controls. Other newly identified methodological problems included the poorly assessed famine intensity, unsuitable study settings for famine research, and poor confounding adjustment. Interpretation: The current estimates of a positive relationship between prenatal exposure to the Chinese famine and adult T2D are mainly driven by uncontrolled age differences between famine births and postfamine births. Studies with more rigorous methods, including age-balanced controls and robust famine intensity measures, are needed to quantify to what extent the famine exposure is related to current T2D patterns in China.

There has been a limited recognition of hypertension and diabetes in China which has compromised optimal treatment. It is not clear if a screening program implemented by a national health survey has improved awareness and management of these conditions. The China Health and Retirement Longitudinal Study (CHARLS) is an ongoing longitudinal health survey conducted since 2011 among Chinese people aged 45 years and older. Participants have been assessed every two years by interviews, physical examinations, and fasting glucose samples were taken in 2011. In 2013 and 2015, participants were asked about awareness and management of selected chronic diseases, and they first became aware of these conditions. Of the 11,000+ participants screened in 2011, 4594 were identified with hypertension and 1703 with diabetes by medical examinations. Over 80% of the middle-aged and elderly Chinese diagnosed with hypertension and/or diabetes in 2011 reported in 2015 that they were unaware of the disease(s). Although some improvement was observed between 2011 and 2015, the main reason for the increase in awareness was a medical examination initiated by the study participant (over 75%), by their work unit or community (12–15%), and rarely (less than 3%) by the CHARLS examination. Participants with a rural household registration status and lower BMI were the most likely to be unaware and to remain unaware of their condition(s). Disease screening in CHARLS did not lead to significant improvements in awareness of hypertension and diabetes. Improvements should be made by the systematic feedback of screening results to survey participants and the monitoring of disease awareness over time. This will be essential to improve disease recognition and facilitate optimal management.

Although the flipped classroom model has been widely adopted in medical education, reports on its use in graduate-level public health programs are limited. This study describes the design, implementation, and evaluation of a flipped classroom redesign of an introductory epidemiology course and compares it to a traditional model. One hundred fifty Masters-level students enrolled in an introductory epidemiology course with a traditional format (in-person lecture and discussion section, at-home assignment; 2015, N = 72) and a flipped classroom format (at-home lecture, in-person discussion section and assignment; 2016, N = 78). Using mixed methods, we compared student characteristics, examination scores, and end-of-course evaluations of the 2016 flipped classroom format and the 2015 traditional format. Data on the flipped classroom format, including pre- and post-course surveys, open-ended questions, self-reports of section leader teaching practices, and classroom observations, were evaluated. There were no statistically significant differences in examination scores or students’ assessment of the course between 2015 (traditional) and 2016 (flipped). In 2016, 57.1% (36) of respondents to the end-of-course evaluation found watching video lectures at home to have a positive impact on their time management. Open-ended survey responses indicated a number of strengths of the flipped classroom approach, including the freedom to watch pre-recorded lectures at any time and the ability of section leaders to clarify targeted concepts. Suggestions for improvement focused on ways to increase regular interaction with lecturers. There was no significant difference in students’ performance on quantitative assessments comparing the traditional format to the flipped classroom format. The flipped format did allow for greater flexibility and applied learning opportunities at home and during discussion sections.

The short-term impact of famines on death and disease is well documented, but estimating their potential long-term impact is difficult. We used the setting of the man-made Ukrainian Holodomor famine of 1932–1933 to examine the relation between prenatal famine and adult type 2 diabetes mellitus (T2DM). This ecological study included 128,225 T2DM cases diagnosed from 2000 to 2008 among 10,186,016 male and female Ukrainians born from 1930 to 1938. Individuals who were born in the first half-year of 1934, and hence exposed in early gestation to the mid-1933 peak famine period, had a greater than twofold likelihood of T2DM compared with that of unexposed controls. There was a dose-response relationship between severity of famine exposure and increase in adult T2DM risk.

To test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944 to 1945, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life.

Inflammation plays an important role in the genesis, progression, and manifestation of cardiovascular diseases (CVDs).¹ C-reactive protein (CRP), an acute phase protein produced by the liver, is one of the most extensively studied systemic markers of inflammation. The CRP increases within a few hours after an inflammatory trigger, peaks in 2 days, and decreases rapidly with the resolution of inflammation. Over the past three decades, extensive epidemiological and clinical evidence has linked the concentration of CRP to major CVDs.^2–4 Since the 2000s, multiple cardiology organizations across the world have recommended adding CRP as an adjunct to assess or predict risks for CVDs.^5–8 However, the role of CRP in CVDs among human populations, especially whether a causal relationship between them exists, remains unclear. This leads to substantial debates on whether CRP can be used as a therapeutic target for CVDs.^9–13