**6. Epidemiology studies**

*Cardiorespiratory Fitness*

larvae [28].

**4. Biological evidences**

**5. Thrifty hypothesis**

protein found in the skin, hair, and nails.

the product of epigenetic modification. Keratinocyte cells are the building blocks of the skin. They are the most common type of skin cell and make keratin, a

One condition that causes the pancreas to stop producing adequate enzymes is pancreatic acinar atrophy. This occurs because the disease hurts slowly and without obvious symptoms. The ability of many animals is adaptability to environmental evolution. This can make small size and slow metabolism to live and survive, while the enlarged size and accelerated metabolism are advantages of reproductive success when resources are available. Often this occurs early in life or even through inheritance from parents and even grandparents. However, fetuses who are adjusting to one environment, such as the uterus, may be at risk when exposed to other environment when they become adults [27]. Effects of prenatal exposure to the Dutch famine on adult disease in later life. Bees determine the number of larvae within the appropriate age group and begin to place these larvae to become queens. The only difference between the honeybees and the queen is the food received during the process of maturity: the workers feed potential queens royal jelly throughout their lives, while the bees are working on royal jelly during the first 2 days of the

Biological evidence may be relevant to understanding human development and susceptibility to disease. With the improved nutritional status of many mothers around the world, the characteristics of their offspring—such as body size and metabolism—also changed. Their mother's prenatal response may generally respond to individuals so that they are more appropriate to the environment's expectations through the signals available in early life. If the mother is a smoker during pregnancy, it is possible that the third generation of her offspring will be smokers. Ironically, however, rapid improvements in nutrition and other environmental conditions may have adverse effects on the health of those whose parents and grandparents lived in poor conditions, as happened in World War II in Europe [29] and the famine in India early in the last century [30]. The full understanding of the patterns of human plasticity in response to early nutrition and other environ-

The thrifty gene hypothesis indicates that certain populations may have genes that determine increased fat storage, which in times of famine represent a survival advantage, but in a modern environment result in obesity and type 2 diabetes. An example of the thrifty hypothesis showed by Dutch famine study which has shown that the offspring of mothers who were pregnant during the famine have more diabetes and those who were exposed in early gestation have more atherogenic lipid profile, altered clotting, more obesity, and a threefold increase in cardiovascular disease. Explanations for the heritability of these syndromes and the environmental contribution to disease susceptibility are addressed by the "thrifty genotype" and the "thrifty phenotype" hypotheses [27]. The underlying scientific hypothesis has been developed by epidemiology studies and emphasized by Dr. David Barker in the United Kingdom. During development fetuses respond to severe malnutrition by favoring the metabolic demands of the growing brain/CNS and heart at the expense of other tissues [31, 32]. In addition, the growing brain/CNS and heart tissue may

mental factors will have implications for public health management.

**42**

Epidemiology studies have shown that markers of malnutrition such as frank intrauterine growth retardation (IUGR), low birth weight, or small for gestation age (SGA) strongly predict the subsequent occurrence of hypertension, hyperlipidemia, insulin resistance, type 2 diabetes, and ischemic heart disease, in adult life.

It has been shown that fetuses that are growth retarded during the first trimester of development are three times more likely to be obese as adults. In the case of premature infants, at the age of 4–10 years, these children who had been born prematurely had an increase in their acute insulin response, which compensated for insulin resistance. This decrease in insulin sensitivity may predispose premature infants to type 2 diabetes mellitus in adulthood, as already demonstrated among infants born at term who are SGA [33, 34], that compared with young people from the same region of Finland who are born after a pregnancy, and young people who ranged from 18 to 27 years of age who were preterm infants have become higher in chronic insulin resistance and more prone to glucose and high blood pressure [35]. Preterm births happen on their own early means that some of what would be the third trimester is lost. This is typically a sensitive period for programming and certainly a time during which the final aspects of organogenesis occur. This is explained by spending in the more difficult environment of a hospital setting in which there are many toxic substances as well as nutritional challenges. Now that many more extremely premature babies are surviving to adulthood, ensuring their health is crucial [36]. On the other hand excessive energy supply to the fetus or infant also has adverse consequences so a U shape works similarly at the tow ends of the malnutrition (**Figure 1**).

Maternal hyperglycemia may lead to fetal hyperinsulinemia and fat deposition that influence the fetus. Offspring of obese women or women with diabetes are at greater risk for developing metabolic disorders themselves, even during childhood [37–39].

As a consequences, an infant usually has about 5–6 billion fat cells during the third trimester when a mother is pregnant. This number increases during early childhood and puberty, resulting in a healthy adult body possessing 25–30 billion fat cells [40]. Meanwhile, excessive energy supply to the fetus or infant will increase the potential of becoming obese. Babies who depend on milk factory have the highest amount of energy, leading to an increase in body weight than children who were breastfed; it can affect the increase in obesity and its risks later in life [41]. This complicate the long-term effects due to Prenatal and postnatal nutrition during early infancy. In one study, carotid intima-media thickness at 9 years of age in 216 children of European ancestry whose mothers had energy intake in the lowest quartile during early or late pregnancy was higher than that of children whose mothers had intake in the highest quartile, implying that maternal nutrition during pregnancy can affect the subsequent risk of atherogenesis in the offspring [42].

Thus, obesity comes from an increase in the numbers of fat cells, or adipocytes, and is hence due to a shift in the activity of certain genes during development. Because to maternal malnutrition during pregnancy, the offspring later suffering from obesity in the middle of the abdomen and lack of muscle mass, change the sensitivity of insulin, change in hepatic metabolism, decreased number of nephrons, high blood pressure, with a change in appetite regulation, activity level, and control of nerve endocrine glands [42]. There are critical periods in the differentiation and maturation of the tissues and cells involved in organogenesis throughout gestation and early postnatal life. The examples of the kidney, heart, and pancreas were obvious since their functional units are formed prenatally in the human fetus [43].
