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(a)Axial unenhanced computed tomography (CT) image. Hepatic attenuation values are 25-50 HU, suggesting that the patient has a fatty liver.(b)Visceral fat area measurement by a CT slice at the L4-L5 level. Visceral fat area (blue) 92.7 cm2; subcutaneous fat area (red) 253.8 cm2; and visceral fat area/subcutaneous fat area ratio 0.37.sure to a low-nutrition environment. Therefore, full- term FGR/SGA and preterm infants have similar risks of developing lifestyle-related diseases3).In the late 1980s, Barker et al. reported an epide-miological cohort study in England and Wales that included more than 15,000 newborns and found that LBW infants appeared to have an increased risk of significantly higher mortality from cardio-vascular events (Barker’s hypothesis)1), following researches determined association with obesity, impaired glucose tolerance, impaired lipid metabo-lism, and hypertension in adulthood4, 5, 6, 7). However, Barker’s hypothesis did not adequately account for acquired factors and intergenerational transmis-sion of disease risk. Later, Gluckman et al. devel-oped Barker’s hypothesis and proposed the Devel-opmental Origin of Health and Disease (DOHaD) theory8). The DOHaD theory is that environmental factors such as placental insufficiency, maternal overnutrition or undernutrition during fertilization, fetal life, and early postnatal life lead to predictive adaptive responses (PARs), and that a mismatch with the actual postnatal environment is a risk factor for future disease8).Recent progress in epigenetic research have led to a better understanding of the molecular biology of the DOHaD hypothesis. Animal studies have suggested that various environmental factors during the developmental period may lead to epigenetic changes, such as DNA methylation and histone modifications, and they may be associated with future health and disease risk9). In recent years, it has become clear that both underfeeding and overfeeding during the fetal period could be related to the risk for developing metabolic syndrome10, 11, 12). Meta-analyses from Europe and the United States have shown that the lowest risk of developing metabolic diseases is associated with birth weight of 3.3-4.5 kg, for every 0.5 kg drop in birth weight, the risk of hypertension, diabetes mellitus, and ischemic heart disease increases by about 10%7). In this review, we introduce the DOHaD theory by exemplifying specific course of an adolescent born FGR/SGA who presented with obesity, impaired glucose tolerance, abnormal lipid metabolism, and hypertension from school age.513Figure 1Lifestyle-related diseases describable by the An 11-year-old Japanese boy visited our hospital with the complaint of proteinuria identified at a regular health check at his school. He was born at the 31st week of gestational age weighing 880 g [-5.1 standard deviation (SD)] due to pregnan-cy-induced hypertension. His mother was neither obese nor a smoker. Although his mental develop-ment was normal, he began to be obese around the age of 4 years, and finally proteinuria appeared at the age of 10 years. His height and weight at the first visit were 150.3 cm and 60.1 kg, respectively, [body mass index (BMI), 26.6 kg/m2], and his blood pressure was 128/50 mmHg. Physical exam-ination showed stretch marks and acanthosis nigri-cans due to obesity. Laboratory analysis [standard value] showed elevated hepatic enzyme levels (alanine aminotransferase (ALT): 185 [6–43] U/L), hyperinsulinemia (insulin 31.5 [2.2-12.4] μU/mL, homeostatic model assessment for insulin resis-tance (HOMA-IR) 17.7 [<1.6]), hyperglycemia (blood sugar 228 [65-109] mg/dL, HbA1c 10.7 [4.6-6.2] %), dyslipidemia (total cholesterol 202 [<200] mg/dL, high-density lipoprotein cholesterol (HDL-C) 31 [>35] mg/dL, low-density lipoprotein cholesterol (LDL-C) 135 [<130] mg/dL, triglycerides 268 [<150] mg/dL), and hyperuricemia (uric acid 7.7 [3.5-6.9] mg/dL). Urinalysis showed protein-uria (urine total protein/urine creatinine 1.97 [<0.2] g/g Cre; urine albumin/urine creatinine 1,275 [<30] mg/g Cre) and urine sugar (semi-quan-DOHaD theory: A case presentation