The three major non-modifiable risk factors responsible for DMII include intrauterine exposure, family history, and ethnicity (9). These factors contribute towards the development of this lethal disease in their respective unique manner.

The most prominent factor of genetic nature responsible for childhood DMII is intrauterine exposure to maternal diabetes (10). However, the diabetes caused in the young infant is DMI, DMII, or gestational diabetes. Medically it has been proven that maternal hyperglycemia and unstable balance between insulin and glucose are the core factors responsible for DMII in young infants (11). Despite advancements in the medical management of blood glucose levels of the mother during pregnancy, it has been observed that intrauterine exposure to maternal diabetes is lethal for infants. The resultant pathologies observed in children who have developed DMII are hyperglycemia, macrosomia, together with the association of improper development of the endocrine system (11).

The state of hyperglycemia in the pregnant mother with diabetes leads to continuous exposure of high levels of glucose to the developing fetus throughout the pregnancy (11). The route of increased glucose transfer to the fetus occurs via the umbilical cord, which in turn stimulates the developing pancreas to elevate insulin secretion in order to prevent hyperglycemia. Thus, the infants that are born under these circumstances are usually adapted to high glucose levels (12,13). Therefore, the unavailability of high glucose levels following birth results in decreased insulin production in newborn infants and these marked changes in the environment and glucose intake cause premature insulin resistance in childhood, which essentially constitutes a growth point for the development of DMII (14). In addition, the above abnormal conditions directly affect the young endocrine control in the infant, leading to associated pathological states in the near future as discussed earlier in this study. The severity as well as duration of the hyperglycemic conditions of the mother determine the extent of DMII disease in the newborn infant.

The condition of abnormally high birth weight in neonates is medically known as macrosomia. The excessive weight is usually the result of the mother's defective endocrine system or the effects of existing metabolic syndrome. Diabetic mothers who undergo treatment and whose glucose levels are well-controlled by medical personnel may give birth to a child with overweight or macrosomic infant (15). The causative factor responsible for the conditon of macrosomia is the rapid and continuous formation of fat tissue in the infant despite regulated glucose levels in the mother. Previous findings confirmed that an infant's adipose growth is directly affected by intrauterine metabolic factors that cause malfunctioning of the infant endocrinal system (16).

As mentioned above, exposure to abnormally high glucose levels in the mother result in impaired endocrine development in neonates. The important molecular step involved in disturbing the normal physiological system of a young infant is the excess production of insulin by the infant endocrine system, leading to the state of hyperinsulinism (17). The initiation of hyperinsulinism in the first trimester greatly affects the neural development of the infant as this period is crucial for brain development. Hyperinsulinism at this stage direclty results in a faulty hypothalamic center that under normal circumstances regulates endocrine function. This results in significant growth maladaptation in the growing infant, which leads to childhood DMII (18). The above associated complications of the endocrine system along with DMII condition in these young infants makes them a high-risk population of individuals with strong possiblities of having obesity and other associated diseases in their adult life (19).

Family history of the disease is a crucial factor responsible for the spread of DMII among neonates. Children with an immediate family member that has been diagnosed with this pathological state are at high risk for the development of childhood DMII as the genetic makeup of the infant promotes the feasibility of this lethal disease (20,21). In mathematical terms, the approximate percentage of risk of development of DMII is 40% when one of the parents is affected with diabetes. On the other hand, when both the parents have diabetes, the likelihood of development of DMII in neonates increases to 70% (22). The genetic makeup of affected parents basically promotes obesity in the young patient, which in turn is useful in the diagnosis of DMII. A previous study suggested the possibility of a confirmed genetic factor, such as a gene or transcription factor, responsible for control of glucose intake and insulin regulation (23). Previous findings indicated an association of TCF7L2 and MTNR1B genes with the development of DMII (24). Thus, it is crucial for children of affected parents to get screened early in order that proper treatment planning can be undertaken in a timely manner. Early diagnosis of DMII is one of the major research hotspots and the stress is on the identification of highly specific genetic markers for the diagnosis of DMII in young infants.

Irreversible factors are responsible for DMII. Reversible factors are also crucial in the spread of diabetes. These factors can be controlled by human, contributing to the well-being of diabetic patients. The lifestyle of an individual is the self-contained factor that can be modified by the individuals themselves (25). Other factors in children for which parents are responsible include diet and breast feeding.

The proper health of a child is the result of proper breastfeeding in his/her infancy (26). Improper breastfeeding is a prime factor responsible for the development of obesity and metabolic syndrome in future (27). Studies have identified a 24% decrease in the risk of prevalence of childhood DMII and associated obesity in children with access to proper breastfeeding (28). Furthermore, a systemic review of 17 studies has revealed a direct correlation between duration of breastfeeding and risk of development of childhood DMII and obesity in neonates (29). One of these 17 studies (29) emphasized that children in the 9–14-year age group who were breastfed for longer durations were not affected by obesity or any other metabolic syndrome disease, including childhood DMII (29). Thus, breastfeeding is an important aspect in the prevention of this chronic disorder.

Obesity is the second major reversible factor responsible for this pathological state. Weight is the deciding criterion for distinguishing high- and low-risk children of developing DMII. Children of a healthy weight are less likely to be affected by childhood DMII as opposed to obese children who are at high risk. There is also a direct interdependence of obesity with childhood DMII (30). The important linking factor between obesity and DMII is insulin resistance, which results in the excess of free fatty acids (FFAs) in obese infants (31). These excess of FFAs in obese infants contribute towards lipolytic activity, an important causative factor for DMII, as discussed in earlier sections. On the other hand, decline in physical activity also promotes insulin resistance (32). By increasing physical activity the growth of muscle volume can be stimulated, resulting in enhanced glucose transport and a decrease in insulin demand. In this manner, enhanced physical activity promotes the efficient utilization of glucose intake and maintains a check over the development of DMII (33). Modification of diet risk of development of DMII is also greatly reduced. Previous findings have shown that excessive intake of carbohydrates in diet favoured the development of childhood DMII (34).

There are significant long-term efffects of childhood DMII, such as life-threatening pathologies including peripheral neuropathy (35,36). Cardiac complications, renal failure, and vision impairment are other well-reported complications of DMII.

Common complications associated with DMII are cardiac ones. Important cardiac alterations in the literature included cardiomyocyte-altered metabolism, changes in cardiac insulin signaling, general calcium control and the stimulation of vascular as well as cardiac fibrosis (37). Fibrotic build up along with overworking of cardiac muscles is also common among DMII patients (38). These complications lead to other well-known complications of cardiac pathology including hyperlipidemia, coronary artery disease, hypertension and diabetic cardiomyopathy (6,39). Previous findings suggested that 50% of infants confirmed with DMII usually develop cardiac complications such as contractility dysfunction and cardiac autonomic neuropathy (40).

The renal complications associated with DMII are also frequently recorded and are mainly the result of poor flow of blood towards kidneys, a condition medically termed chronic kidney disease (41). The condition of hyperglycemia results in damage of masangial cells that ultimately blocks kidney function. This function blockage of the kidneys leads to albuminuria (42).