#92454: Type 2 Diabetes in Youth: A Growing Concern

Diabetes is a chronic illness that affects 38.4 million people in the United States[1]. The vast majority have type 2 diabetes, a condition that usually affects people older than 45 years of age. While type 1 diabetes accounts for about 5% of all diagnosed diabetes, an estimated 352,000 individuals younger than 20 years of age in the United States are diagnosed with type 2 diabetes every year [2]. Although the numbers do not suggest an epidemic, they do represent an unprecedented worldwide rise in type 2 diabetes among children and adolescents over the past 30 years. Prevalence increases with age, tripling between 10 to 14 years of age and 15 to 18 years of age. For reasons that remain unclear, adolescent girls have a 60% higher prevalence rate than adolescent boys [3]. The Centers for Disease Control and Prevention (CDC) has projected that type 2 diabetes in persons younger than 20 years of age in the United States will increase 673% by 2060 [4]. Unfortunately, the rise in incidence of type 2 diabetes among youth is accompanied by a severe shortage of pediatric endocrinologists [5].

In the United States, the incidence of type 2 diabetes is greater in children of certain ethnic groups [3]. Among youth 10 to 19 years of age, type 2 diabetes represents 4.5% of the cases of diabetes in Non-Hispanic White individuals, 37.8% in Non-Hispanic Black individuals, 20.9% in Hispanics, 11.9% in Asian/Pacific Islanders, and 32.8% among Native Americans [6]. The problem is not limited to the United States. In fact, indigenous children around the world bear the greatest burden of youth-onset type 2 diabetes [3,7]. There is considerable variation in the prevalence of type 2 diabetes depending upon ethnicity and geographical region. Rates are lowest in Europe but increasing in China and India, which is concerning, given their large populations [8,9].

The potential burden of type 2 diabetes in youth is enormous. This disease is associated with serious, long-term complications, such as blindness, end stage renal disease, lower extremity amputation, and the development of cardiovascular disease. Experts believe that the progression of the disease in children may be more rapid and more severe than in adults [3]. In addition to the more well-known consequences of uncontrolled diabetes, research indicates that obese adolescents with type 2 diabetes may have diminished cognitive performance and brain abnormalities as indicated by magnetic resonance imaging studies. These brain abnormalities include reduced white matter and an increased amount of cerebrospinal fluid space [10,11,12].

Diabetes accounts for an overall economic burden of more than $413 billion annually, including a disproportionate use of hospital inpatient care, outpatient and physician office care, emergency visits, skilled nursing days, and home health visits [1]. In addition to these economic costs, diabetes takes an incalculable toll on the individual in terms of lost productivity, disability, decreased quality of life, and early mortality. People with diabetes have healthcare costs that are more than two times greater than those without diabetes [13].

The majority of spending for diabetes goes toward the treatment of long-term complications, such as blindness, renal failure, heart disease, hypertension, and amputation [1]. When the disease begins earlier in life, it is more likely to require more protracted treatment with increased economic, social, and personal burden. Furthermore, many children with type 2 diabetes are undiagnosed due to the asymptomatic nature of the disease, increasing the risk for undetected and untreated long-term complications.

Why has there been an escalation in the prevalence of type 2 diabetes in this previously unaffected population? The answer to this question appears to be closely related to features of our modern way of life. Increased body weight is strongly associated with type 2 diabetes in youth, pointing to lifestyle as a causative factor. Childhood obesity has more than tripled since the 1970s [14]. It is anticipated that obesity will affect the health of 91 million children worldwide by 2025 [15].

Modern eating habits are characterized by the consumption of calorie-laden convenience foods that are high in fat and sugar and low in fiber. Studies have shown that children and adolescents with type 2 diabetes eat more saturated fat than recommended and have inadequate intake of fiber, grains, fruits, and vegetables [16]. Not surprisingly, the combination of these factors has resulted in high rates of overweight and obesity in all age groups, including children. Excessive consumption of foods high in fat and sugar and low in fiber is associated with substantial increases in the risk for diabetes. Obesity alone can have serious consequences for children, including an increased risk for early adult cardiovascular disease.

Adequate physical activity in young people is essential in preventing type 2 diabetes. It is well known that exercise not only helps offset adiposity but enhances insulin sensitivity in young people [17]. In addition to poor eating habits, children have fewer opportunities to burn calories on a daily basis. Television, computers, telephones, and electronic devices provide the primary source of leisure activity for most young people today, while the typical family does not engage in physical activity sufficient to offset the consumption of high-calorie diets. According to government statistics, only 25% of students in grades 9 through 12 are engaged in an adequate amount of moderate-intensity physical activity [18]. Further, coronavirus disease 2019–2020 (COVID-19) increases risk factors for obesity in youth due to increased stress related to academic and social changes as well as decreased physical activity. Online education does not provide physical education classes, recess time, and normal levels of active movement for school-aged children and adolescents [19].

The correlation between obesity, sedentary lifestyle, and type 2 diabetes is clear. Obesity and inactivity are known to significantly impair the body's ability to utilize insulin. This results in a condition known as insulin resistance, which plays an important role in the development of type 2 diabetes and its associated complications.

In the United States, an estimated 97.6 million people older than 18 years of age have prediabetes [1]. Although more study is needed, it is estimated that about one in six adolescents have prediabetes [1]. Prediabetes is defined by a blood glucose level that is higher than normal but not high enough to meet the diagnostic criteria for diabetes. Having prediabetes greatly increases the risk for later development of type 2 diabetes, and most people with type 2 diabetes have had prediabetes prior to the onset of diabetes.

The American Diabetes Association defines persons at increased risk for diabetes (prediabetes) as those with impaired fasting glucose and/or impaired glucose tolerance and/or A_1c 5.7% to 6.4%. Prediabetes should not be viewed as a clinical entity in its own right but rather as an increased risk for diabetes and cardiovascular disease.

(https://diabetesjournals.org/care/issue/47/Supplement_1 Last Accessed: February 19, 2024)

Level of Evidence: Expert Opinion

Prediabetes is an asymptomatic condition and can only be detected by laboratory testing. Prediabetes includes any one of the following findings of increased risk for diabetes [20]:

The harmful effects of high blood glucose begin at much lower levels than those established to define diabetes. In other words, complications of diabetes begin early in the course of glucose intolerance—often before diabetes is diagnosed. Studies suggest that when blood glucose is higher than normal and remains untreated, patients have a greater risk for developing the microvascular and macrovascular complications associated with diabetes [21,22,23]. Research confirms that long-term damage to the body, especially to the heart and circulatory system, can occur during prediabetes [24]. Although many patients with prediabetes may inevitably develop type 2 diabetes, the Diabetes Prevention Program (DPP) has shown that it is possible to delay or even avoid progression completely by implementing lifestyle modification that leads to healthy weight loss [25]. Healthcare professionals must provide preventive care to individuals who have prediabetes in order to minimize the impact of this condition.

The CDC defines diabetes as, "a chronic (long-lasting) health condition that affects how your body turns food into energy" [26]. The CDC divides the various existing types of diabetes into three main classes [26]:

The majority of cases are either type 1 or type 2 diabetes. Other types of diabetes include diabetes that are chemically induced or that occur from genetic defects, other diseases, or infections.

Previously, type 1 was known as "juvenile-onset" diabetes, while type 2 was referred to as "adult onset" diabetes. However, these terms are no longer appropriate due to the fact that children and adolescents are now developing what was formerly known as adult onset diabetes in increasing numbers.

Type 2 Diabetes

When diagnosing diabetes in a child or young person, the National Guideline Alliance recommends assuming type 1 diabetes unless there are strong indications of type 2 diabetes. The possibility of type 2 diabetes should be considered in children and young people with suspected diabetes who:

• Have a strong family history of type 2 diabetes

• Are obese at presentation

• Are of black or Asian family origin

• Have no insulin requirement or have an insulin requirement of less than 0.5 units/kg body weight/day after the partial remission phase

• Show evidence of insulin resistance (e.g., acanthosis nigricans)

(https://www.nice.org.uk/guidance/ng18 Last Accessed: February 19, 2024.)

Level of Evidence: Expert Opinion

Because it is a relatively new phenomenon, there is still much to learn about the epidemiology and pathophysiology of type 2 diabetes in children. While it closely resembles that of adults, youth-onset type 2 diabetes displays unique aspects, such as rapidly progressive beta-cell decline and accelerated development of diabetes complications [20,27,28]. According to the CDC, type 2 diabetes in children is usually diagnosed between 10 and 19 years of age. Risk factors include obesity, having a family member with type 2 diabetes, and being born to a mother with gestational diabetes. After 10 years of age, being a member of minority populations, such as Hispanic, African American, Asian/Pacific Islander, and American Indian, greatly increases the risk for development of type 2 diabetes in youth [29]. Whether it occurs in adults or children, most cases of type 2 diabetes begin with insulin resistance. In this condition, the pancreas initially continues to produce insulin, but the tissues are unable to use it. This may be due to a scarcity of receptors on the cells or because the receptors do not function well. Reasons for poorly functioning receptors include adiposity, muscular inactivity, and genetic factors. The beta cells of the pancreas respond to insulin resistance by producing even more insulin in an attempt to compensate. However, much of the insulin remains unused and blood levels of insulin are temporarily high (hyperinsulinemia). After a period of manufacturing large amounts of insulin, the beta cells of the pancreas eventually become exhausted, the amount of endogenous insulin greatly declines, and clinical diabetes ensues. In some cases, type 2 diabetes can be managed with a combination of diet, exercise, and oral medications. Many times, insulin therapy is required to control blood glucose levels and to prevent long-term complications of the disease. Individuals with type 2 diabetes usually produce enough insulin to prevent ketoacidosis. Therefore, they are not truly "insulin dependent," even if they do use insulin therapy to control blood glucose.

The distinction between type 1 and type 2 diabetes in children can sometimes be difficult and complicated. Since the 1980s, the rates of both type 1 and type 2 diabetes in children have increased concurrently with obesity rates in children. Autoantigens and ketosis are often present in young patients with type 2 diabetes, pointing to the possibility that obesity may be driving the autoimmune beta-cell failure that underlies type 1 diabetes [20,30]. Furthermore, type 2 diabetes in children is often not detected until glucose levels are extremely high, with resulting ketoacidosis, a condition most commonly found in type 1 diabetes [31]. While challenging, proper diagnosis at onset is critical for the education and treatment of the patient.

Uncontrolled hyperglycemia over a number of years is known to cause damage to the small vessels that supply the retina of the eye (retinopathy), the nephrons of the kidney, and the motor, sensory, and autonomic nerves. There is evidence that these complications are especially aggressive in young people with type 2 diabetes; they are also highly prevalent [32,33,37]. The United Kingdom Prospective Diabetes Study demonstrated that intensive treatment of type 2 diabetes in adults can significantly lower the risk for developing diabetes-related eye, kidney, and nerve disease. The findings from this study included a 25% reduction of microvascular disease in subjects who maintained long-term glycemic control [38].

The development of serious large vessel disease is also a possible effect of diabetes. Macrovascular complications of diabetes involve the cardiovascular, cerebral vascular, and peripheral vascular systems, leading to high incidences of myocardial infarction, stroke, and lower extremity disease.

While the injurious effects of hyperglycemia on large blood vessels are believed to play a significant role in the development of large vessel disease, hyperinsulinemia is also responsible for other damaging effects to the cardiovascular system. Resulting from insulin resistance, high levels of insulin in the blood are associated with a series of adverse metabolic changes that greatly increase the risk for cardiovascular disease; these changes characterize the metabolic syndrome. This cluster of disorders includes two major independent risk factors for myocardial infarction: hypertension and dyslipidemia.

A person has metabolic syndrome if he or she has any three of the following risk factors [39,40]:

The presence of metabolic syndrome is a signal of the need for lifestyle modification. Weight loss, exercise, and a low-fat diet can often improve metabolic abnormalities without medication. Even a reduction in sitting time and sedentary pastime can have a positive effect metabolic risk factors [40].

Acanthosis nigricans is a skin condition characterized by brownish-black patches, usually found on the back of the neck, in the axillae, and on areas exposed to repeated friction. They are slightly raised lesions that feel velvety to touch. Presence of the condition is considered a marker of hyperinsulinemia, and it develops in some cases of type 2 diabetes in children. This sign is most frequently recognized in obese, dark-skinned individuals and occurs more frequently in Native Americans, African Americans, and Hispanics when compared to White or Asian-origin individuals [43]. Parents of children with this condition often mistake acanthosis nigricans for poor hygiene and attempt to treat it with vigorous scrubbing and topical medications or cleansers. Some schools have initiated screening procedures for acanthosis nigricans, as many obese children who go on to develop type 2 diabetes present with only this sign [31].

PCOS is a disorder of the female reproductive system and is closely associated with insulin resistance. It is characterized by chronic anovulation, resulting in scanty or infrequent menstruation. In patients with PCOS, estrogen levels are usually normal while androgen levels are high. The elevated androgen levels can result in acne and hirsutism [44].

Nonalcoholic fatty liver disease is a chronic inflammatory process of the liver often associated with insulin resistance. Chronic hepatic inflammation can lead to liver dysfunction and ultimately failure. Evaluation for nonalcoholic fatty liver disease should be done at the time that type 2 diabetes is diagnosed in a child and annually thereafter [7].

The American Diabetes Association (ADA) recommends the screening of asymptomatic high-risk youth for type 2 diabetes every three years, beginning at 10 years of age or the onset of puberty, whichever occurs first. For the purposes of screening criteria, the ADA considers children at high risk if they are overweight (BMI ≥85th percentile) or obese (BMI ≥95th percentile) and have one or more of the following additional risk factors [20]:

The diagnostic criteria for diabetes in youth are the same as those established for adults and can be assessed using any of the tests listed in Table 3.

A family-centered approach is recommended for treating type 2 diabetes in youth[20,46]. Many families are greatly challenged by the lifestyle changes that are necessary to manage type 2 diabetes in children. Changes in daily habits, such as those involving food and activity, are difficult for people in general because they reflect embedded psychologic, social, and cultural influences. Therefore, psychologists, social workers, registered dieticians, and exercise physiologists play valuable roles in the interdisciplinary diabetes care team. Readiness to change refers to the theory that people move through a series of stages as they give up unhealthy behaviors and adopt those that are health-enhancing. James Prochaska's behavioral change model has been widely used in many areas of health education, including in diabetes self-management. There are five identified stages that people go through when they are trying to change behaviors (Table 5). For each stage of change, certain interventions on the part of the healthcare provider are recommended. By employing these interventions, healthcare professionals can help "meet" the families within their own particular stage of change at any given time[47].

According to the AAP, parenting skills are the key to success in treating childhood obesity. They recommend the following parental interventions in helping to change behavior in children [48]:

Diabetes care professionals should routinely ask the patient/family whether they are feeling overwhelmed or stressed by the diabetes diagnosis as distress can lead to resistance to and/or interruption of treatment [20]. Indications for referral to a qualified behavioral and/or mental health professional include positive screening for overall stress related to work-life balance, diabetes, distress, management difficulties, depression, anxiety, disordered eating, and cognitive dysfunction [20].

A family approach to health education is essential, as the lifestyle changes required to manage the child's diabetes will have an impact on the entire family. Parental education should include an assessment of existing knowledge about eating, weight, and health. Research has indicated that most parents of obese or overweight children do not consider their children overweight and do not believe that this is a health problem [49]. Therefore, many will need help in understanding that the child is overweight and that the problem must be addressed. Furthermore, there may be a misconception, especially in some cultures, that being overweight is a sign of good health. If this is the case, there will be a need to educate parents regarding the dangers of diabetes and heart disease related to being overweight in a culturally sensitive way.

In addition to lifestyle modification, comprehensive education for young people with type 2 diabetes and their families should include the following components:

Self-monitoring of blood glucose (SMBG) provides immediate feedback on the impact of various daily influences, such as food, activity, and medications, on blood glucose levels. For many individuals, this is an empowering activity that provides a sense of control in the management of the disease. By keeping blood glucose levels near normal as much as possible, patients with diabetes can reduce their risk for acute and chronic complications.

Children and adolescents with type 2 diabetes should monitor their blood glucose levels frequently to assess the quality of their control. The AAP recommends that patients with newly diagnosed type 2 diabetes perform fingerstick blood glucose monitoring before meals and at bedtime until glycemic control is achieved [46].

Target ranges for children with type 2 diabetes who monitor blood glucose are not specified in the practice guidelines published by the ADA and the ISPAD, except to say that they should be individualized [20]. As stated, a reasonable A1c target for most children and adolescents with type 2 diabetes is <7% [20]. As with adults, the overall goal is to maintain blood glucose as close to normal as much as possible, without excessive hypoglycemia, and to prevent long-term complications.

Achieving and maintaining a reasonable body weight is the major therapeutic goal in the management of type 2 diabetes in youth. Other goals of medical nutrition therapy include normalizing blood glucose (without excessive hypoglycemia) and maintaining healthy lipid and blood pressure values while allowing for normal growth and development [16,20].

Even minor reductions in weight can significantly improve blood glucose control. A weight-loss plan for a child should be developed and supervised by a registered dietician to ensure a nutritionally adequate meal plan that allows for growth and development while moderately restricting calories [31]. The ADA recommends that overweight/obese youth with type 2 diabetes and their families be provided with a developmentally and culturally appropriate comprehensive lifestyle program that is integrated with diabetes management and that aims to achieve a 7% to 10% decrease in excess weight [20].

Clinic-based weight management programs appear to be effective in improving the metabolic profile of obese children, if they remain in a supervised program for several years. Results of a pilot program in Philadelphia suggest that an informal, nonintensive program of regular clinician contacts over two years can be more effective than intensive time-limited programs. In this study, the greatest improvements in children's metabolic profile correlated with frequency of visits to the healthcare provider [50].

The safest and most efficacious method for losing weight is to decrease caloric intake from fat and sugar while increasing fiber intake and physical activity [7]. Although weight loss is the goal, the primary focus of treatment should be on healthy eating and physical activity. Nutrition for youth with type 2 diabetes (and for all youth) should focus on healthy eating patterns that emphasize the consumption of nutrient-dense, high-quality foods and decreased consumption of calorie-dense, nutrient-poor foods, particularly sugar-added beverages [20]. Providing the family with restrictive lists of forbidden and allowable foods is not recommended. Instead, overall changes in lifestyle should be promoted [20]. Encouraging positive changes in food consumption patterns improves the chances of successful, long-term weight management by working on the modification of unhealthy behaviors. Family involvement in the nutritional management plan is vital for the successful implementation of behavior changes in the child. This supports the patient with diabetes and treats or prevents obesity and obesity-related health conditions in the entire family.

An appropriate meal plan is based upon an assessment that includes family preferences, timing and location of meals and snacks, cultural preferences and restrictions, food preparation practices, and readiness to change. Dietary recommendations should always be culturally appropriate and sensitive to the financial situation of the family. In order to be successful, a weight-loss program requires frequent interaction with the patient, continuous monitoring, and positive reinforcement. Counseling interventions should include encouraging family-style meals that are low in fat and smaller in portion size [20]. It is also important to help the family increase its awareness of their snacking behaviors and to offer strategies for making healthy changes. Because many people engage in eating that has nothing to do with hunger, families should be offered tactics for changing these habits as well.

Guidelines for facilitating healthy eating-related behaviors in youth include:

Physical activity counteracts both insulin resistance and obesity, making it an essential component for both the prevention and treatment of type 2 diabetes. Physical activity and exercise also help improve obesity-related risk factors in youth (e.g., proinflammatory state, metabolic health) [52,53,54]. A study presented at the 2010 ADA annual meeting revealed that obese boys who engaged in aerobic and resistance exercise decreased their total body fat, visceral fat, and insulin resistance, even without any changes in diet. The study also indicated that resistance exercise training is appealing to boys and that it expends similar energy to aerobic training in this population [55].

The CDC and the ADA recommend that children and adolescents get at least 60 minutes of physical activity every day [20,56]. Children should be encouraged to participate in sustained activities that use large muscle groups on a daily basis. Aerobic exercise should make up most of the 60 minutes of daily exercise. This should include vigorous intensity exercise at least three days per week. Children should have muscle-strengthening exercise at least three days per week as part of their 60 minutes per day [20]. This could include push-ups and climbing on playground equipment. Bone-strengthening exercise is recommended three days per week, included in the 60 minutes per day requirement [20]. Bone-strengthening exercises include weight-bearing exercise, such as jumping rope and running.

Extended periods of inactivity should be avoided. A 2010 study showed that adolescent boys with two or more hours a day of television or computer screen time are at greater risk for insulin resistance and other markers of metabolic syndrome [57]. A 2017 study found several factors that contribute to prolonged screen time and physical inactivity, including the youth's socioeconomic status, unhealthy food habits, and urban residence (with less exposure to other children) [58]. Overall physical activity can be increased by helping young people find ways to be more active in everyday activities, such as using stairs instead of the elevator, walking instead of riding, and playing outside as much as possible.

Because they are typically not motivated by long-term benefits, young people will not usually be interested in exercising for health reasons. Instead, activities must offer the immediate reward of being fun as well as developmentally appropriate. Physical activities that an adolescent or child may enjoy include dancing, jumping rope, swimming, skating, skateboarding, and team sports. Children and adolescents who have been sedentary should increase activity levels in increments to reach the overall recommendation of 60 minutes per day [18].

Family involvement in the activity plan is recommended to provide support to the child with diabetes and to promote the overall health of the family [16]. Exercising with others, such as parents and friends, promotes the pleasurable aspects of the program and validates its importance [58]. Because finding time to exercise can be challenging for many families, quality school programs that encourage physical activity are also very important. Children should be encouraged to participate in as many different sports as possible. Most importantly, the child must enjoy whatever activities are being encouraged to ensure that he or she will want to continue with them on a regular and consistent basis.

Reduced exercise tolerance is a problem in most overweight children with type 2 diabetes. Walking is considered one of the best forms of activity for those who are exercise intolerant. Walking regimens must be started slowly and engaged in for short periods of time to build tolerance.

Obese children are likely to be uncomfortable participating in organized sports activities. Therefore, other ways of being active should be encouraged. Obese children should begin with a limitation on access to television and increasing non-weight-bearing activities such as swimming, cycling, and paced walking [18].

Evidence suggests that type 2 diabetes in youth is different not only from type 1 diabetes but also from type 2 diabetes in adults. Additionally, given the current obesity epidemic, distinguishing between type 1 and type 2 diabetes in children can be difficult[20]. Accurate diagnosis is critical. Although general treatment goals for patients with the two diagnoses are the same, specific treatment regimens differ markedly between patients with type 1 and type 2 diabetes.

The ADA recommends the initiation of pharmacologic therapy, in addition to lifestyle therapy, at diagnosis of type 2 diabetes[20]. Insulin therapy should be initiated for children and adolescents who are ketotic, in diabetic ketoacidosis, or whose disease cannot be clearly identified as either type 1 or type 2 diabetes[3,7,20]. After acidosis is resolved, metformin should be initiated while subcutaneous insulin therapy is continued[20]. Patients treated with insulin therapy who do not meet glycemic targets should be moved to multiple daily injections with basal and premeal bolus insulins[20]. Patients initially treated with insulin and metformin who meet glucose targets (based on SMBG) can be tapered over two to six weeks by decreasing the insulin dose 10% to 30% every few days[20].

In 2023, the U.S. Food and Drug Administration (FDA) approved empagliflozin (Jardiance) and empagliflozin plus metformin (Synjardy) for use in the treatment of type 2 diabetes in children 10 years of age and older [59]. The safety and efficacy of empagliflozin in children were studied in a double-blind, randomized, placebo-controlled trial in 157 patients 10 to 17 years of age with inadequately controlled type 2 diabetes. Participants were randomly assigned to one of three treatment arms for 26 weeks: empagliflozin, a DPP-4 inhibitor (linagliptin), or placebo. At the beginning of the trial, 51% of patients were taking metformin alone, 40% of patients were taking a combination of metformin and insulin, 3% of patients were taking insulin alone, and 6% of patients were not taking other medicines for diabetes. The trial found that, at week 26, treatment with empagliflozin was superior in reducing hemoglobin A1ccompared with placebo. Patients treated with empagliflozin also had reductions in fasting plasma glucose, compared to patients taking placebo [59]. Jardiance and Synjardy received FDA approval in 2014 and 2015, respectively, as an adjunct to diet and exercise for treatment of type 2 diabetes in adults [59,60].

Table 6 lists various medications used in the treatment of type 2 diabetes, although many are not labeled for use in children. Metformin and insulin are approved for children with type 2 diabetes[20,31]. In addition, the GLP-1 agonists dulaglutide, extended-release exenatide, and liraglutide are approved for use in children 10 years of age and older if glycemic targets are not met with metformin (with or without insulin) and if the child's medical and family history allow[20,60]. In metabolically stable patients, metformin, if not contraindicated and if tolerated, is the preferred initial pharmacologic agent for the treatment of type 2 diabetes[20].

Metformin acts by decreasing the amount of glucose produced by the liver and improving insulin sensitivity. For adolescents using metformin, it is important to screen for alcohol abuse, including binge drinking, as this medication is contraindicated in those with moderate-to-heavy alcohol use. Besides being effective in lowering blood glucose levels, metformin has other advantages:

When monotherapy with metformin does not result in appropriate glucose control after three months, other oral medications such as thiazolidinediones, sulfonylureas, incretin mimetics, or sodium-glucose co-transporter 2 inhibitors may be added. Further, insulin may be used alone or with oral medications[7,20]. A combination of metformin plus rosiglitazone has been found to be more effective than metformin alone[34]. Use of medications not approved by the FDA for youth with type 2 diabetes is not recommended outside research trials[20].

The most common and serious side effect of using insulin is hypoglycemia. An important consideration in any age group, it is of special concern in children because they are believed to be less careful about preventing and recognizing the symptoms[62]. When insulin is used, parents and children must be educated on the signs, symptoms, causes, and treatment of hypoglycemia (Table 7).

Oral contraceptive agents with low androgenic activity are often prescribed to normalize menstrual cycles in cases of PCOS. Metformin can also increase menstrual regularity. Often prescribed in tandem, oral contraceptives and metformin appear to work synergistically in normalizing reproductive function. Metformin should be prescribed with caution in sexually active young women with PCOS, as this could increase the risk for unplanned pregnancy. Counseling on abstinence, safer sex practices, and birth control options is strongly indicated in teens.

The prevention and control of long-term complications in young patients with diabetes is of vital importance due to the increased risks associated with earlier disease onset. The coexistence of obesity, hypertension, and dyslipidemia, which are common in children with type 2 diabetes, greatly increases the risk for cardiovascular disease. Because of the seriousness of these complications, hypertension and dyslipidemia must be aggressively treated and should be considered as important as blood glucose control. These comorbidities are often already present at the time of diagnosis. Therefore, the ADA recommends that blood pressure measurement, fasting lipid profile, microalbuminuria assessment, and dilated eye exam be performed at the time of diagnosis [20]. In addition to cardiovascular risk, hypertension is a risk factor for the development of eye and kidney disease. Routine preventive care can often delay or slow the progression of complications by ensuring early treatment. The routine preventive care schedule recommended for all patients with diabetes consists of [3,7,20]:

Careful control of blood pressure is imperative for the prevention of early-onset cardiac and renal disease in this population [20]. One large study concluded that strict blood pressure management in adults with type 2 diabetes was related to a significant reduction in cardiovascular morbidity, including a 44% reduction in stroke and a 56% reduction in heart failure [63]. Therefore, blood pressure should be monitored regularly and treated aggressively in children with diabetes when either the diastolic or systolic reading is consistently at or above the 95th percentile for age, sex, and height [20]. Nonpharmacologic measures to reduce blood pressure include dietary intervention and physical activity aimed at weight control. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) should be initiated for treatment of confirmed hypertension. Patients of childbearing potential should be advised that these medications have potential teratogenic effects and pregnancy should be avoided while taking them [20].

ACE inhibitors are generally considered first-line pharmacologic agents to treat hypertension in young people with type 2 diabetes [20]. These agents are preferred because, in addition to their lowering effects on blood pressure, they are known to have an independent renal protective function when microalbuminuria is present.

Dyslipidemia outweighs all other risk factors for the development of cardiovascular disease in adults with type 2 diabetes. There is increasing evidence that the atherosclerotic process is present in childhood, beginning as early as 10 years of age [64]. Lipid disorders occur comorbidly in most people with type 2 diabetes, including children. Like hypertension, lipid disorders must be treated aggressively. Optimal goals for children and adolescents are LDL-C less than 100 mg/dL, HDL-C greater than 35 mg/dL, and triglycerides less than 150 mg/dL [20].

First-line therapy for dyslipidemia includes lifestyle management aimed at optimizing glucose control and weight loss through healthy eating and increased physical activity. If LDL-C remains greater than 130 mg/dL after six months of dietary intervention, treatment with statins is indicated, with a goal of LDL-C less than 100 mg/dL [20].

The American Heart Association has established these dietary recommendations for preventing cardiovascular disease [51]:

Parents still take major responsibility for the healthcare needs of school-aged children, including responsibility for what foods are eaten. However, the school-aged child's environment is expanding, with more activities out of the home and away from parents. The importance of the peer group and fear of being different from others are basic developmental issues in this age group. At the same time, these children are especially impressionable to the examples set by parents and other adults. As adolescence approaches, the importance of body image intensifies. Children at this age also begin experimenting with independent decision making and may begin to challenge authority. By 12 years of age, most children can manage their own insulin therapy, but parents must supervise to ensure that doses are not missed or forgotten.

Even without having to face a chronic illness, adolescence is a complex time for many. Major issues during this stage of life include hormonal fluctuations and sexual development, changes in body image, and strong peer influences. The struggle for independence from parents and other authority figures may lead some adolescents to ignore treatments and falsify blood glucose results. Basic identity issues are important during this time and extend into young adulthood. Risk-taking is a characteristic at this stage, and substance abuse is a well-known related problem. Substance misuse may interfere with the treatment plan and can even be the source of dangerous interactions if the patient is using certain types of medications to manage diabetes. Healthcare providers should be aware of these developmental issues and plan to spend quality, one-on-one time with adolescents to explore the barriers to self-care that are perceived by the patient. Parents need support and guidance during this time as well.

Some parents may think that the recommended lifestyle changes may be too difficult for the child to handle. They may also feel sorry for the child and fear that the child is fragile due to his or her illness. In this case, they may respond inappropriately by failing to place limits on the child's eating or by forgoing blood glucose monitoring because it hurts. If parents seem overindulgent, the appropriate intervention is to explore the reasons why they behave this way. Are they afraid? Do they lack confidence? Do they feel guilt? What is their readiness to change? Feelings of fear or lack of confidence can often be overcome with education and support. Teach parents that their behavior may be reinforcing their child's own sense of inadequacy. Always identify the stage of change that the family is in and provide interventions accordingly.

Some parents may cope by trying to achieve perfection in meeting therapeutic goals. This is manifested by rigid adherence to diet and unrealistically expecting blood glucose values to be within the target range all of the time. In these cases, parents should be educated that their child's self-esteem may be threatened by the overemphasis on treatment. They can also be educated that it is appropriate to make compromises in the meal plan as long as the overall eating pattern is healthy. For example, cake and ice cream for a birthday may add calories and raise blood sugar, but consumption of these types of food can occasionally be accommodated by working them into the entire day's meal plan and by maintaining or increasing physical activity.

Reassure these parents that "ideal" control is not necessary all of the time, and encourage them to work with the child for the best control. Also educate parents that blood glucose target ranges are usually guidelines to strive for and that occasional out-of-range results will not adversely affect health in the long run. Caution them to avoid words like "cheating" and "bad blood sugar," as this may be construed by the child as personal failure or misbehavior. Parents and healthcare providers can help the child avoid some of these detrimental feelings by reminding him or her that the target levels are used as a guide and are not a reflection of failure [67].

As youth move from childhood to adolescence, diabetes management is gradually shifted from parent to child. However, this shift often occurs more abruptly as teens enter the developmental stage that theorists refer to as "emerging adulthood"—a critical period between 18 and 25 to 30 years of age [20,68,69]. This is generally the time when youth begin to leave their parents' home and must become fully responsible for their diabetes care. These responsibilities include diabetes self-management, making medical appointments, and financing health care (if they are no longer covered by their parents' insurance plans). It is also a time associated with a deterioration in glycemic control; increased occurrence of acute complications; psychosocial, emotional, and behavioral challenges; and the emergence of chronic complications [70,71,72,73]. The transition from pediatric to adult health care often leads to fragmented healthcare delivery, which negatively impacts healthcare quality, cost, and outcomes [74].

To facilitate a seamless transition from pediatric to adult health care, comprehensive, coordinated planning for the transition should begin in early adolescence, preferably at least one year prior to the expected date of transition [20,75,76]. A discussion of the challenges faced during this period and specific recommendations for managing them may be found in the ADA position statement Diabetes Care for Emerging Adults: Recommendations for Transition From Pediatric to Adult Diabetes Care Systems[71]. Additionally, the Endocrine Society, in collaboration with the ADA and other organizations, has developed transition tools for clinicians, youth, and families that may be accessed at https://www.endocrine.org/improving-practice/transitions [76].