Globally, the number of people with diabetes mellitus has quadrupled in the past three decades, and diabetes mellitus is the ninth major cause of death. About 1 in 11 adults worldwide now have diabetes mellitus, 90% of whom have type 2 diabetes mellitus (T2DM). Asia is a major area of the rapidly emerging T2DM global epidemic, with China and India the top two epicentres. Although genetic predisposition partly determines individual susceptibility to T2DM, an unhealthy diet and a sedentary lifestyle are important drivers of the current global epidemic; early developmental factors (such as intrauterine exposures) also have a role in susceptibility to T2DM later in life. Many cases of T2DM could be prevented with lifestyle changes, including maintaining a healthy body weight, consuming a healthy diet, staying physically active, not smoking and drinking alcohol in moderation. Most patients with T2DM have at least one complication, and cardiovascular complications are the leading cause of morbidity and mortality in these patients. This Review provides an updated view of the global epidemiology of T2DM, as well as dietary, lifestyle and other risk factors for T2DM and its complications.

Global aetiology and epidemiology of type 2 diabetes mellitus and its complications.

Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations. Type 2 diabetes mellitus (T2DM) and prediabetes are increasingly observed among children, adolescents and younger adults. The causes of the epidemic of T2DM are embedded in a very complex group of genetic and epigenetic systems interacting within an equally complex societal framework that determines behavior and environmental influences. This complexity is reflected in the diverse topics discussed in this Review. In the past few years considerable emphasis has been placed on the effect of the intrauterine environment in the epidemic of T2DM, particularly in the early onset of T2DM and obesity. Prevention of T2DM is a 'whole-of-life' task and requires an integrated approach operating from the origin of the disease. Future research is necessary to better understand the potential role of remaining factors, such as genetic predisposition and maternal environment, to help shape prevention programs. The potential effect on global diabetes surveillance of using HbA(1c) rather than glucose values in the diagnosis of T2DM is also discussed.

The worldwide epidemiology of type 2 diabetes mellitus--present and future perspectives

Context With increasing globalization and East-West exchanges, the increasing epidemic of type 2 diabetes in Asia has far-reaching public health and socioeconomic implications. Objective To review recent data in epidemiologic trends, risk factors, and complications of type 2 diabetes in Asia. Evidence Acquisition Search of MEDLINE using the term diabetes and other relevant keywords to identify meta-analyses, systematic reviews, large surveys, and cohort studies. Separate searches were performed for specific Asian countries. The review was limited to English-language articles published between January 1980 and March 2009; publications on type 1 diabetes were excluded. Evidence Synthesis The prevalence of diabetes in Asian populations has increased rapidly in recent decades. In 2007, more than 110 million individuals in Asia were living with diabetes, with a disproportionate burden among the young and middle aged. Similarly, rates of overweight and obesity are increasing sharply, driven by economic development, nutrition transition, and increasingly sedentary lifestyles. The “metabolically obese” phenotype (ie, normal body weight with increased abdominal adiposity) is common in Asian populations. The increased risk of gestational diabetes, combined with exposure to poor nutrition in utero and overnutrition in later life in some populations, may contribute to the increasing diabetes epidemic through “diabetes begetting diabetes” in Asia. While young age of onset and long disease duration place Asian patients with diabetes at high risk for cardiorenal complications, cancer is emerging as an important cause of morbidity and mortality. Conclusions Type 2 diabetes is an increasing epidemic in Asia, characterized by rapid rates of increase over short periods and onset at a relatively young age and low body mass index. Prevention and control of diabetes should be a top public health priority in Asian populations.

Diabetes in Asia: epidemiology, risk factors, and pathophysiology.

The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.

/pdf/sex-and-gender-differences-in-risk-pathophysiology-and-1p8mzg4br6.pdf

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus.

Mendelian randomisation (MR) estimates causal effects of modifiable phenotypes on an outcome by using genetic variants as instrumental variables, but its validity relies on the assumption of no pleiotropy, that is, genes influence the outcome only through the given phenotype. Excluding pleiotropy is difficult, but the use of multiple instruments can indirectly address the issue: if all genes represent valid instruments, their MR estimates should vary only by chance. The Sargan test detects pleiotropy when individual phenotype, outcome and genotype data are measured in the same subjects. We propose an alternative approach to be used when only summary genetic data are available or data on gene-phenotype and gene-outcome come from different subjects. The presence of pleiotropy is investigated using the between-instrument heterogeneity Q test (together with the I(2) index) in a meta-analysis of MR Wald estimates, derived separately from each instrument. For a continuous outcome, we evaluate the approach through simulations and illustrate it using published data. For the scenario where all data come from the same subjects, we compare it with the Sargan test. The Q test tends to be conservative in small samples. Its power increases with the degree of pleiotropy and the sample size, as does the precision of the I(2) index, in which case results are similar to those of the Sargan test. In MR studies with large sample sizes based on summary data, the between-instrument Q test represents a useful tool to explore the presence of heterogeneity due to pleiotropy or other causes.

/pdf/detecting-pleiotropy-in-mendelian-randomisation-studies-with-35bwnzdwhi.pdf

Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome.

Context Low birth weight is implicated as a risk factor for type 2 diabetes. However, the strength, consistency, independence, and shape of the association have not been systematically examined. Objective To conduct a quantitative systematic review examining published evidence on the association of birth weight and type 2 diabetes in adults. Data Sources and Study Selection Relevant studies published by June 2008 were identified through literature searches using EMBASE (from 1980), MEDLINE (from 1950), and Web of Science (from 1980), with a combination of text words and Medical Subject Headings. Studies with either quantitative or qualitative estimates of the association between birth weight and type 2 diabetes were included. Data Extraction Estimates of association (odds ratio [OR] per kilogram of increase in birth weight) were obtained from authors or from published reports in models that allowed the effects of adjustment (for body mass index and socioeconomic status) and the effects of exclusion (for macrosomia and maternal diabetes) to be examined. Estimates were pooled using random-effects models, allowing for the possibility that true associations differed between populations. Data Synthesis Of 327 reports identified, 31 were found to be relevant. Data were obtained from 30 of these reports (31 populations; 6090 diabetes cases; 152 084 individuals). Inverse birth weight–type 2 diabetes associations were observed in 23 populations (9 of which were statistically significant) and positive associations were found in 8 (2 of which were statistically significant). Appreciable heterogeneity between populations (I 2  = 66%; 95% confidence interval [CI], 51%-77%) was largely explained by positive associations in 2 native North American populations with high prevalences of maternal diabetes and in 1 other population of young adults. In the remaining 28 populations, the pooled OR of type 2 diabetes, adjusted for age and sex, was 0.75 (95% CI, 0.70-0.81) per kilogram. The shape of the birth weight–type 2 diabetes association was strongly graded, particularly at birth weights of 3 kg or less. Adjustment for current body mass index slightly strengthened the association (OR, 0.76 [95% CI, 0.70-0.82] before adjustment and 0.70 [95% CI, 0.65-0.76] after adjustment). Adjustment for socioeconomic status did not materially affect the association (OR, 0.77 [95% CI, 0.70-0.84] before adjustment and 0.78 [95% CI, 0.72-0.84] after adjustment). There was no strong evidence of publication or small study bias. Conclusion In most populations studied, birth weight was inversely related to type 2 diabetes risk.

https://jamanetwork.com/journals/jama/articlepdf/183130/jrv80019_2886_2897.pdf

Birth Weight and Risk of Type 2 Diabetes: A Systematic Review

The fetal programming theory that birth weight contributes to blood pressure or body size in later life is examined in this study. A prospective longitudinal study was conducted on subjects who were examined as newborns and prospectively interviewed and re-examined at 11 to 14 years old. Low birth weight (<2500 g) was present in 36% of the sample. The adolescent examination included measurements of blood pressure (BP), both auscultation and oscillometric methods; anthropometrics (height, weight, and body mass index [BMI]); health status; and health behaviors. Data were analyzed on 250 subjects. Correlation coefficients of birth weight with all BP measures were nonsignificant, except for the last auscultated diastolic BP (r=0.19, P<0.01), which had a positive relationship. The simple correlation coefficients of birth weight with adolescent body size were significant and positive for weight and BMI. After multiple linear regression analyses with adjustments for age, Tanner stage, and gestational age, there was no significant effect of birth weight on adolescent weight or BMI. No significant correlations were detected for ponderal index at birth with adolescent measures. This study, which includes a substantial portion of low-birth-weight cases (36%), indicates that birth weight does not correlate negatively with later BP. These results do not support the low-birth-weight theory and indicate that childhood factors that are more proximal have a greater effect on adolescent BP than intrauterine factors.

Effect of Birth Weight on Blood Pressure and Body Size in Early Adolescence

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Birth Weight and Risk of Type 2 Diabetes: A Systematic Review

Effect of Birth Weight on Blood Pressure and Body Size in Early Adolescence