Pediatric Type 2 Diabetes Mellitus 

Updated: Feb 28, 2017
Author: Alba E Morales Pozzo, MD; Chief Editor: Sasigarn A Bowden, MD 

Overview

Practice Essentials

Although type 2 diabetes is widely diagnosed in adults, its frequency has markedly increased in the pediatric age group since the end of the 20th century. Most pediatric patients with type 2 diabetes belong to minority communities. A simplified scheme for the etiology of type 2 diabetes mellitus is shown in the image below.

Simplified scheme for the pathophysiology of type Simplified scheme for the pathophysiology of type 2 diabetes mellitus.

Signs and symptoms

Distinguishing between type 1 and type 2 diabetes at diagnosis is important. Typical characteristics of type 2 diabetes include the following:

  • Slow and insidious onset

  • Most common in overweight or obese patients from a minority group (Native Americans, blacks, and Pacific Islanders)

  • Signs of insulin resistance

  • Strong family history of type 2 diabetes: Familial lifestyle risk factors leading to obesity may be present, as may a family history of cardiovascular disease or metabolic syndrome

Physical findings may include the following:

  • Obesity (strongly associated with type 2 in children and adolescents)

  • Acanthosis nigricans

  • Polycystic ovary syndrome

  • Hypertension

  • Retinopathy

See Clinical Presentation for more detail.

Diagnosis

Testing for type 2 diabetes should be considered when a patient is overweight and has any 2 of the following[1] :

  • Family history of type 2 diabetes in first-degree or second-degree relative

  • Minority race or ethnicity (eg, American Indian, black, Hispanic, Asian or Pacific Islander)

  • Signs of insulin resistance or conditions associated with insulin resistance (eg, acanthosis nigricans, hypertension dyslipidemia, PCOS)

Recommendations for screening are as follows:

  • Initial screening may begin at age 10 years or at onset of puberty if puberty occurs at a young age

  • Screening should be performed every 2 years

  • A fasting plasma glucose test is the preferred screening study; if clinical suspicion is high but fasting blood glucose is normal (< 100 mg/dL), an oral glucose tolerance test should be considered

Glucose values may be interpreted as follows:

  • A random plasma glucose concentration of 200 mg/dL or greater in association with polyuria, polydipsia, or unexplained weight loss is diagnostic of diabetes[2]

  • In an asymptomatic patient, a fasting plasma glucose value of 126 mg/dL or greater or a 2-hour plasma glucose value of 200 mg/dL or greater during an oral glucose tolerance test is also diagnostic of diabetes[2]

Other laboratory results that usually suggest type 2 diabetes are as follows:

  • Elevated fasting C-peptide level

  • Elevated fasting insulin level

  • Absence of autoimmune markers (glutamic acid decarboxylase [GAD] and islet cell antibodies)[2]

Testing for albuminuria can be done by means of 1 of the following 3 methods:

  • Measurement of the albumin-creatinine ratio in a random spot collection

  • A 24-hour collection for albumin and creatinine determinations, which allows simultaneous measurement of creatinine clearance

  • Timed (eg, 4-hour or overnight) collection

Fasting lipid profiles should be obtained after stable glycemia is achieved and every 2 years thereafter if normal. Optimal values for children with type 2 diabetes are as follows[3] :

  • Triglycerides < 150 mg/dL

  • Low-density lipoprotein (LDL) < 100 mg/dL

  • High-density lipoprotein (HDL) >35 mg/dL

See Workup for more detail.

Management

The goal of therapy is to achieve and maintain euglycemia and near-normal hemoglobin A1c (HbA1c) levels (< 7%). More specifically, glycemic and nonglycemic goals may include the following[4] :

  • Fasting glycemia of less than 126 mg/dL

  • Resolution of polyuria, nocturia, and polydipsia

  • Healthy body weight

  • Maintenance of cardioprotective levels of lipids and blood pressure (LDL level < 100 mg/dL, triglyceride < 150 mg/dL, HDL level >35 mg/dL; blood pressure < 95th percentile for age, sex, and height)

  • Participation of the whole family as a unit

Treatments for pediatric type 2 diabetes include the following:

  • Diabetes education and lifestyle changes (diet, exercise, weight control)

  • Pharmacologic therapy with metformin, insulin, a sulfonylurea, or another hypoglycemic agent

  • Lipid-lowering agents and blood pressure medications to achieve cardioprotection, if necessary

To protect these patients from future cardiovascular disease, treatment should emphasize the following:

  • Improvement of glycemia, dyslipidemia, and hypertension

  • Weight management

  • Prevention of short- and long-term complications

  • Blood glucose monitoring 2-3 times daily (more often when insulin treatment is being adjusted)

  • Evaluation every 3 months at the diabetes clinic (more often, as necessary, when treatment is being adjusted)

HbA1c values should be monitored at each quarterly visit. HbA1c testing has the following advantages over glucose measurement:

  • It captures long-term glucose exposure

  • It has less biologic variability

  • It does not require fasting or timed samples

  • It is currently used to guide management decisions

Additional monitoring should be performed as follows:

  • Microalbuminuria and fasting lipid profile (annually)

  • Dilated eye examination (annually)

  • Blood pressure evaluation and careful neurologic examination (at each clinic visit)

See Treatment and Medication for more detail.

Background

In the past, type 2 diabetes mellitus was very rare in pediatric patients. However, coinciding with the increasing prevalence of obesity among American children, the incidence of type 2 diabetes in children and adolescents has markedly increased, to the extent that it now accounts for as many as one third of all new cases of diabetes diagnosed in adolescents. This trend is particularly pronounced in minority racial and ethnic groups. (See Epidemiology.)[5]

Complications

Although the natural history of type 2 diabetes mellitus in children is not well studied, the experience accumulated over years of treating adults may help to minimize the occurrence of complications in children. (See Prognosis and Clinical.)

Acute complications of type 2 diabetes include hyperglycemia, diabetic ketoacidosis, hyperglycemic-hyperosmolar state,[6] and hypoglycemia. Complications from insulin resistance include hypertension, dyslipidemia, and polycystic ovarian syndrome (PCOS).[7]

As many as 4% of patients with type 2 diabetes initially present in a hyperglycemic-hyperosmolar coma, which can lead to cerebral edema and death if not promptly recognized and treated.[6]

Long-term complications of type 2 diabetes mellitus include the following:

  • Nephropathy

  • Neuropathy

  • Retinopathy

  • Coronary artery disease

A retrospective study found that adults diagnosed with type 2 diabetes before age 45 years have a much higher risk of cardiovascular disease relative to age-matched control subjects. The investigators concluded that early onset type 2 diabetes appears to be a more aggressive disease from a cardiovascular standpoint. (See Prognosis, Clinical, and Treatment.)[8]

Etiology

In individuals without diabetes, approximately 50% of their total daily insulin is secreted during basal periods to suppress lipolysis, proteolysis, and glycogenolysis. In response to a meal, rapid insulin secretion (also called first-phase insulin secretion) ensues. This secretion facilitates the peripheral use of the prandial nutrient load, suppresses hepatic glucose production, and limits postprandial elevations in glucose levels. The second phase of insulin secretion follows and is sustained until normoglycemia is restored. A simplified scheme for the etiology of type 2 diabetes mellitus is shown in the image below.

Simplified scheme for the pathophysiology of type Simplified scheme for the pathophysiology of type 2 diabetes mellitus.

Type 2 diabetes spans a continuum from impaired glucose tolerance and impaired fasting glucose to frank diabetes that results from progressive deterioration of insulin secretion and action. Although the first phase of insulin response is markedly reduced early in the course of the disease, ongoing disorganized basal insulin secretion associated with deterioration of peripheral insulin action occurs during the progression from normal to impaired glucose tolerance to frank diabetes.[9]

In parallel, as a result of decreased insulin sensitivity in the liver, endogenous glucose output increase adds to the already hyperglycemic milieu, worsening peripheral insulin resistance and beta cell function. Failure of the beta cell to keep up with the peripheral insulin resistance is the basis for the progression from impaired glucose tolerance to overt clinical type 2 diabetes. Longitudinal studies have demonstrated that during the transition between normal glucose tolerance to diabetes, 31% of a person's insulin-mediated glucose disposal capacity, as well as 78% of his or her acute insulin response, is lost.

The UK Prospective Diabetes Study found that beta cell function was 50% of normal at the time of diagnosis of type 2 diabetes in adults.[10] A case study of the progression of diabetes in an adolescent female found an almost 15% decline in beta cell function per year over the 6-year duration of diabetes, with no substantial changes in insulin sensitivity.[11] Further prospective studies in young persons with type 2 diabetes are needed in order to clarify the mechanism of disease in this population.

Risk factors

The major risk factors for type 2 diabetes in young persons are as follows:[12]

  • Obesity and inactivity, which are important contributors to insulin resistance

  • Native American, black, Hispanic, Asian, or Pacific Islander descent

  • Family history of type 2 diabetes in first- and second-degree relatives

  • Age of 12-16 years, the mean age range of onset of type 2 diabetes in youths - These ages coincide with the relative insulin resistance that occurs during pubertal development

  • Low birth weight and high birth weight[13]

  • Maternal gestational diabetes or type 2 diabetes[14, 15]

  • Not breastfed during infancy[16]

In a retrospective cohort study of more than 43,000 individuals, study participants who were prescribed antipsychotics were significantly more likely to develop type 2 diabetes within the first year of use compared with matched controls who were not prescribed these medications. The risk increased with higher medication doses and remained elevated for up to 1 year after the medications were discontinued. The association between antipsychotic use and type 2 diabetes remained highly significant when only participants younger than 18 years were assessed.

The study included 28,858 first-time users of antipsychotic medications and 14,429 matched control individuals who had recently initiated use of a psychotropic other than an antipsychotic, all from the Tennessee Medicaid program. All participants were 6 to 24 years of age. Antipsychotics used included risperidone, quetiapine, aripiprazole, and olanzapine. Medications used by the control group included mood stabilizers such as lithium, as well as antidepressants, psychostimulants, α-agonists, and benzodiazepines.

A total of 106 study subjects receiving antipsychotics were diagnosed and treated for type 2 diabetes (mean age, 16.7 years; 63% girls), translating into 18.9 cases per 10,000 person-years. Antipsychotic users had a 3-fold increased risk of developing type 2 diabetes by the end of the study compared with the group of nonusers. This risk was significant within the first year of follow-up.[17, 18]

Epidemiology

Occurrence in the United States

Although type 2 diabetes is widely diagnosed in adults, its frequency has markedly increased in the pediatric age group since the end of the 20th century. Depending on the population studied, type 2 diabetes now represents 8-45% of all new cases of diabetes reported among children and adolescents.[19] Most pediatric patients with type 2 diabetes belong to minority communities.

The SEARCH for Diabetes in Youth Study (a US multicenter, observational study conducting population-based ascertainment of cases of diabetes mellitus in individuals over age 20 y) found that the incidence of type 2 diabetes was highest among American Indians aged 15-19 years (49.4 cases per 100,000 person-years). Second and third highest incidence belonged to Asian-Pacific Islanders and blacks, aged 15-19 years, with 22.7 cases per 100,000 person-years and 19.4 cases per 100,000 person-years, respectively.[20]

International occurrence

An increased prevalence of type 2 diabetes has also been recognized in countries other than the United States, including Japan, where the incidence of type 2 diabetes in school children after 1981 was found to be strongly related to an increasing prevalence of obesity.[21] Studies among the Indian, British, Chinese, Taiwanese, Libyan, Bangladeshi, Australian, and Maori populations also have shown increasing incidence of youth-onset type 2 diabetes.[22, 23, 24, 25, 26, 27, 28, 29]

Race-, sex-, and age-related demographics

Type 2 diabetes primarily affects minority populations.[20] From 1967-1976 to 1987-1996, the prevalence of type 2 diabetes increased 6-fold in Pima Indian adolescents and appeared for the first time in children and adolescents younger than age 15 years.[30] Similar increases in prevalence were observed among Japanese, Asian-American, and black children. In several clinics across the United States, pediatric patients with a diagnosis of type 2 diabetes were from minority ethnic groups (black, Asian, and Hispanic groups).

The prevalence of type 2 diabetes in the pediatric population is higher among girls than boys, just as the prevalence is higher among adult females than it is in adult males.[12]

The mean age range of onset of type 2 diabetes is 12-16 years; this period coincides with puberty, when a physiologic state of insulin resistance develops. In this physiologic state, type 2 diabetes develops only if inadequate beta cell function is associated with other risk factors (eg, obesity).[31]

A white paper by the FAIR Health organization that analyzed private claims from more than 21 billion 0- to 22-year-olds found that claim lines with a diagnosis of type 2 diabetes increased 109% between 2011 and 2015. The study also found that although obesity was diagnosed more frequently in females, type 2 diabetes were more frequently diagnosed in males, however, further study is warranted to analyze this association between prevalence of pediatric type 2 diabetes and gender as other studies have found conflicting results.[32, 33]

According to data from the SEARCH for Diabetes in Youth study, the overall prevalence of type 2 diabetes among American youths aged 10-19 years rose by 35% between 2001 and 2009 (from 0.34 per 1000 to 0.46 per 1000). Study data were obtained from 38 counties in five states, as well as American Indian reservations in Arizona and New Mexico, and included young people from several different racial-ethnic backgrounds.

The greatest increase in the prevalence of type 2 diabetes from 2001 to 2009 was observed in Hispanic youths (from 0.45 per 1000 to 0.79 per 1000), followed by blacks (from 0.95 per 1000 to 1.06 per 1000), and whites (from 0.14 per 1000 to 0.17 per 1000).[34] There were no significant changes in prevalence for either American Indians or Asian Pacific Islanders.

Prognosis

After 30 years of postpubertal diabetes, 44.4% of people with type 2 diabetes and 20.2% of people with type 1 diabetes develop diabetic nephropathy. Overall, the incidence of nephropathy has declined among patients with type 1 diabetes since the end of the 20th century; however, it has not for persons with type 2 diabetes.

So far, no population-based follow-up study has been conducted to determine the long-term prognosis of type 2 diabetes among children and adolescents. Mortality rates and standardized mortality ratios in type 2 diabetes are likely higher than those in type 1 diabetes, given that the major cause of death in type 1 diabetes is end-stage renal disease.

Morbidity and mortality/ Complications

Overall, morbidity and mortality associated with type 2 diabetes are related to short-term and long-term complications. A longitudinal, population-based study conducted from 1965-2002 in the Arizona Pima Indian population found that youth-onset type 2 diabetes is associated with substantially increased incidence of end-stage renal disease and mortality in middle age.[35]

In a comparative study among Japanese youths with type 1 and type 2 diabetes, the cumulative incidence of nephropathy among patients with type 2 diabetes was higher than it was in those with type 1 diabetes. Nephropathy also appeared earlier in type 2 diabetes than it did in type 1 diabetes.[36]

The SEARCH for Diabetes in Youth Study found that American youth with type 2 diabetes have a higher prevalence of elevated albumin-to-creatinine ratio (ACR) than do young persons with type 1 diabetes. The study also found that high blood pressure, hyperglycemia, and high triglyceride concentrations are associated with elevated ACR, independent of the type of diabetes.[37] Albuminuria is a risk factor for renal failure in pediatric type 2 diabetics. Youth with type 2 diabetes are at a fourfold increased risk of renal failure compared to pediatric patients with type 1 diabetes.[38]

Among the Pima Indians of Arizona, the risk of retinopathy is lower in patients with youth-onset type 2 diabetes than in those with adult-onset diabetes.[39]

The TODAY study was a recent multicenter clinical trial comparing treatment options in a large cohort of youth with recently diagnosed type 2 diabetes.[40] The trial showed that high rates of complications and comorbidities (hypertension, hyperlipidemia, retinopathy, and microalbuminuria) were already present in during the first few months of diagnosis and the rate of progression of these conditions increased progressively throughout the trial period. In fact, the common complications of type 2 diabetes seen in adults are also found in youth with type 2 diabetes but appear to progress on an accelerated timeline. Consequently, preventive measures, aggressive screening and a high index of suspicion are therefore required in order to curb these negative outcomes that could significantly burden this population during their third and fourth decades of life.[41, 42]

Patient Education

Education is an essential component of the treatment plan in type 2 diabetes; it is a continuing process involving the child, family, and all members of the diabetes team. The following strategies may be used:

  • Appropriate teaching of survival skills at diagnosis

  • Explanation and discussion about the possible causes of type 2 diabetes

  • Discussion about the need for blood glucose monitoring and the importance of compliance with the drug regimen

Practical skills training includes the following:

  • Insulin injections (if insulin is part of the treatment plan)

  • Blood and/or urine testing for ketone bodies

  • Hypoglycemia recognition and treatment

  • Emergency telephone contact procedure

  • Psychosocial adjustment to the diagnosis

  • Importance of regular follow-up

  • Basic dietary advice

Diabetes education is an ongoing process and should address the following issues:

  • Formal education during clinic visits or during diabetes classes

  • Educational holidays and camps

  • Support groups

  • Complications - Use times of crisis or acute complications as opportunities to reinforce the importance of some aspects of self ̶ diabetes management that may have been neglected

Educate the patient about the potential side effects of oral hypoglycemic agents (eg, the presence of ketonuria or of any condition predisposing to the accumulation of lactate in patients on metformin).

With regard to the patient’s sexual health, provide advice about contraception, genital hygiene, sexually transmitted diseases, and fungal infections. In pregnant patients with type 2 diabetes, emphasize the importance of good glycemic control before and during pregnancy and discuss the effect of maternal diabetes on the fetus.

 

Presentation

History

At the time of diagnosis, determining whether a patient has type 1 or type 2 diabetes is important, because patients with type 1 diabetes are totally dependent on exogenous insulin administration for survival, whereas patients with type 2 diabetes do not necessarily require exogenous insulin to survive.[2]

Because of the increasing prevalence of obesity in the pediatric population, the percentage of immune-mediated diabetes in overweight or obese patients is increasing, rendering the distinction between type 1 and type 2 diabetes difficult at times. Blood glucose monitoring is required regardless of the type of diabetes, and treatment with insulin should be started when indicated.[2]

The onset of type 2 diabetes is usually slow and insidious; it most often occurs in overweight or obese patients from a minority group (Native Americans, blacks, and Pacific Islanders). Patients with type 2 diabetes often have signs of insulin resistance, such as hypertension, PCOS,[43] or acanthosis nigricans.

A strong family history of type 2 diabetes is usually reported among affected youth. The families of adolescents with type 2 diabetes often have lifestyle risk factors leading to obesity.[44] In addition, children with type 2 diabetes are more likely to report a family history of cardiovascular disease and/or metabolic syndrome.

Type 1 diabetes occurs in people of all races; its onset is typically acute and severe. Patients with type 1 diabetes are often lean and do not show manifestations of insulin resistance.

Physical Examination

Obesity is strongly associated with type 2 diabetes in children and adolescents. Eighty-five percent of children with type 2 diabetes are either overweight or obese (defined as at or above the 85th percentile of the sex-specific body mass index [BMI] for age-based growth charts).[30]

Acanthosis nigricans, a marker of insulin resistance, is a velvety, hyperpigmented thickening of the skin; it is frequently seen on the nape of the neck and in intertriginous areas; it is found in as many as 90% of children with type 2 diabetes.[30]

PCOS is a reproductive disorder commonly seen in young women with acanthosis nigricans. It is characterized by hyperandrogenism and chronic anovulation. The role of insulin resistance in the etiology of PCOS has been extensively studied, and medications that decrease insulin resistance and/or hyperinsulinemia in women with this syndrome often attenuate the hyperandrogenism and metabolic abnormalities.

Hypertension may occur in children with type 2 diabetes. The risk of macrovascular and microvascular diabetic complications is positively associated with elevated systolic blood pressure.

Ophthalmologic examination should be performed at or shortly after diagnosis to detect incipient retinopathy.

 

DDx

Diagnostic Considerations

Conditions to consider in the differential diagnosis of type 2 diabetes include the following:

  • Atypical diabetes mellitus (ADM)

  • Maturity-onset diabetes of the young (MODY)

  • Diabetes secondary to mutations in mitochondrial deoxyribonucleic acid (DNA)

  • Genetic defects of the beta cell

  • Genetic defects in insulin action

  • Diseases of the exocrine pancreas

  • Endocrinopathies

  • Drug- or chemical-induced diabetes

Differential Diagnoses

 

Workup

Approach Considerations

According to criteria established by the American Diabetes Association, testing for type 2 diabetes should be considered when a patient is overweight (eg, body mass index [BMI] at the 85th percentile for age and sex, weight at the 85th percentile, weight 120% of ideal for height) and any 2 of the following factors exist[1] :

  • Family history of type 2 diabetes in first-degree or second-degree relative

  • Minority race or ethnicity (eg, American Indian, black, Hispanic, Asian or Pacific Islander)

  • Signs of insulin resistance or conditions associated with insulin resistance (eg, acanthosis nigricans, hypertension dyslipidemia, PCOS)

Recommendations for screening are as follows:

  • Initial screening may begin at age 10 years or at onset of puberty if puberty occurs at a young age

  • Screening should be performed every 2 years.

  • A fasting plasma glucose test is the preferred screening study

In children who do not meet the criteria described above but in whom diabetes is highly suspected, clinical judgment should be applied. If clinical suspicion for diabetes is high but a fasting blood glucose level is normal (< 100 mg/dL), an oral glucose tolerance test should be considered as a more sensitive screening tool.

Because the onset of type 2 diabetes frequently precedes the diagnosis by several years, testing for end-organ effects of the disease is important. In addition, perform dilated eye examination for retinopathy shortly after diagnosis and yearly thereafter.

Plasma Glucose and Other Tests

A random plasma glucose concentration of 200 mg/dL or greater in association with polyuria, polydipsia, or unexplained weight loss is diagnostic of diabetes.[2]

In an asymptomatic patient, a fasting (ie, no caloric intake for at least 8 h) plasma glucose value of 126 mg/dL or greater or a 2-hour plasma glucose value of 200 mg/dL or greater during an oral glucose tolerance test is also diagnostic of diabetes.[2]

Fasting C-peptide and insulin levels are usually elevated in type 2 diabetes. Autoimmune markers (glutamic acid decarboxylase [GAD] and islet cell antibodies) are usually negative in type 2 diabetes but are frequently present in type 1 diabetes.[2]

Evaluation for Diabetic Nephropathy

Microalbuminuria is said to be present if urinary albumin excretion is 30 mg/24 h (equivalent to 20 µg/min with a timed specimen or 30 mg of albumin per gram creatinine with a random sample; see Urinalysis). Testing for albuminuria can be performed using 1 of 3 methods, as follows:

  • Measurement of the ACR in a random spot collection

  • A 24–hour collection for albumin and creatinine determinations, which allows for simultaneous measurement of creatinine clearance

  • Timed (eg, 4-h or overnight) collection

Evaluation for Dyslipidemia

Obtain fasting lipid profile after stable glycemia has been achieved and every 2 years thereafter if normal. Optimal lipid levels for children with type 2 diabetes are as follows[3] :

  • Triglycerides optimal level - Less than 150 mg/dL

  • Low-density lipoprotein (LDL) optimal level - Less than 100 mg/dL

  • High-density lipoprotein (HDL) optimal level - More than 35 mg/dL

 

Treatment

Approach Considerations

Ideally, management of diabetes should involve a pediatric endocrinologist, a diabetes nurse educator, a nutritionist, and a behavioral specialist.

In January 2013, the American Academy of Pediatrics (AAP) issued clinical practice guidelines on the management of type 2 diabetes in children and adolescents. The guidelines recommend insulin treatment in all patients who present with ketosis or extremely high blood glucose levels because it may not be clear initially whether these patients have type 2 or type 1 diabetes. Once a diagnosis of type 2 diabetes is confirmed, lifestyle modification and metformin treatment should be initiated.[45, 46]

The goal of therapy is to achieve and maintain euglycemia, as well as near-normal hemoglobin A1c (HbA1c) levels (≤7%). Patients who are not ill at diagnosis can be treated initially with lifestyle changes (eg, diet, exercise, weight control). However, because few patients can maintain euglycemia with lifestyle changes alone, most children and adolescents require medication.[2]

Hemoglobin A1c (HbA1c) levels should be measured every 3 months and treatment adjusted if goals for both HbA1c and blood glucose are not met. Fingerstick self-glucose monitoring is recommended for all patients receiving insulin or sulfonylureas, those starting or changing therapy, and those who have not met treatment goals or who have intercurrent illness.[45, 46]

Insulin therapy is indicated in symptomatic patients with persistent hyperglycemia, the presence of an HbA1c of more than 9%, or ketoacidosis. After blood glucose levels are normalized, efforts to taper insulin with progressive substitution of an oral agent are undertaken.

Glycemic and nonglycemic goals should be clearly stated and may include the following[4] :

  • Fasting glycemia of less than 126 mg/dL

  • Resolution of polyuria, nocturia, and polydipsia

  • Healthy body weight

  • Maintenance of cardioprotective levels of lipids and blood pressure - Ie, LDL level of less than 100 mg/dL, triglyceride level of less than 150 mg/dL, HDL level of greater than 35 mg/dL, blood pressure of less than the 95th percentile for age, sex, and height

  • Participation of the whole family as a unit

Unless an acute complication (eg, recurrent hypoglycemia, persistent ketosis, hyperglycemic hyperosmolar state) occurs or there is poor patient compliance with treatment, type 2 diabetes is usually managed in an outpatient setting.

Recognize that, in patients with PCOS who are receiving metformin, possible resumption of normal ovulation and menstrual cycles increases the risk of pregnancy. Transfer care to an obstetrician when pregnancy is established.

Diet

Referral to a nutritionist with experience in pediatric diabetes is necessary. Dietary recommendations should be culturally appropriate, sensitive to family resources, and provided to all caregivers, especially those in charge of cooking the family's meals.

The entire family should be encouraged to adopt healthier lifestyle habits such as participation in daily exercise and decreasing the intake of high-calorie, high-fat foods.[2]

Activity

A study by Loimaala et al study showed that long-term endurance and strength training resulted in improved metabolic control of type 2 diabetes compared with standard treatment. However, significant cardiovascular risk reduction and conduit arterial elasticity did not improve.[47]

Prevention

Because type 2 diabetes in children and adolescents is strongly associated with obesity and sedentary lifestyle, any intervention designed to increase physical activity and improve dietary habits should be encouraged.[48]

Pharmacologic Therapy

Pharmacologic therapy is indicated when the disease is not well controlled with diet and exercise. Metformin should be the first oral agent used in children and teenagers with an HbA1c level of less than 9%. If metformin is unsuccessful as monotherapy, the addition of insulin, a sulfonylurea, or another hypoglycemic agent may be appropriate.[2]

Lipid-lowering agents, such as 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), and blood pressure medications (ideally, angiotensin-converting enzyme [ACE] inhibitors) should be used if lifestyle modifications are insufficient in achieving cardioprotective levels of lipids and blood pressure. For example, statins may be needed to treat hyperlipidemia patients with type 2 diabetes if their fasting LDL ̶ level goals are not met after 3-6 months of lifestyle modification.[49, 3] ACE inhibitors are the agents of choice to treat hypertension and microalbuminuria.[50]

Proposed Management Algorithm

Diabetes education is indicated, including lifestyle changes to achieve healthy weight goals. First-line therapy is metformin at 1000-2000 mg/d. Goals include a fasting glucose level goal of less than 126 mg/dL and/or an HbA1c level of less than 7%.[4] If goals in step 1 are achieved, continue therapy.

If goals in step 1 not achieved after 3 months (fasting glucose level >126 mg/dL or HbA1c level >7%), add 0.4-0.6 U/kg of 24-hour insulin at bedtime (Glargine or Levemir). If combination therapy is adequate, continue therapy. If combination therapy is inadequate after 3 months, intensify insulin therapy until the fasting plasma glucose level is less than 126 mg/dL and the HbA1c level is less than 7%.

Stroke Prevention

In 2010, the American Heart Association-American Stroke Association released updated guidelines for the primary prevention of stroke. Specific recommendations for patients with diabetes are incorporated in these.[51]

Hypertension

Regular blood pressure screening, lifestyle modification, and drug therapy are recommended. A lower risk of stroke and cardiovascular events are seen when systolic blood pressure levels are less than 140 mm Hg and diastolic blood pressure is less than 90 mm Hg. In patients who have hypertension with diabetes or renal disease, the blood pressure goal is less than 130/80 mm Hg.

Diabetes

Blood pressure control is recommended in type 1 and 2 diabetes. Hypertensives agents that are useful in the diabetic population include ACE inhibitors and angiotensin receptor blockers (ARBs). Treating adults with diabetes with statin therapy, especially patients with other risk factors, is recommended, and monotherapy with fibrates may also be considered to lower stroke risk. Taking aspirin is reasonable in patients who are at high cardiovascular disease risk; however, the benefit of taking aspirin in diabetic patients for the reduction of stroke risk has not been fully demonstrated.

Dyslipidemia

Treating patients with statins is recommended in patients with coronary heart disease or certain high-risk conditions, for the primary prevention of ischemic stroke. In addition to statin therapy, therapeutic lifestyle changes and LDL-cholesterol goals are recommended. Niacin may be used in patients with low HDL cholesterol or elevated lipoprotein (a), but its efficacy in preventing ischemic stroke is not established.

Fibric-acid derivatives, niacin, bile acid sequestrants, and ezetimibe may be useful in patients who have not achieved target LDL levels with statin therapy or who cannot tolerate statins. However, their effectiveness in reducing the risk of stroke has not been established.

Diet

A diet that is low in sodium and high in potassium is recommended to reduce blood pressure. Diets that promote the consumption of fruits, vegetables, and low-fat dairy products, such as the DASH (Dietary Approaches to Stop Hypertension)-style diet, help to lower blood pressure and may lower risk of stroke.

Physical activity

Increasing physical activity is associated with a reduction in the risk of stroke. The goal is to engage in at least 30 minutes of moderate intensity activity on a daily basis.

Long-Term Monitoring

Prevention and treatment of hyperlipidemia and hypertension in individuals with type 2 diabetes are necessary in order to protect these patients from future cardiovascular disease. (The risk for vascular complications and cardiovascular mortality in patients with diabetes mellitus is increased by poor glucose control.) Treatment of type 2 diabetes should target the improvement of glycemia, dyslipidemia, and hypertension, as well as weight management and the prevention of short- and long-term complications.[4] Blood sugar monitoring should be performed 2-3 times daily, and more often than this when insulin treatment is being adjusted.

The patient should be seen every 3 months at the diabetes clinic, and more often, as necessary, when treatment is being adjusted.

Hemoglobin monitoring

HbA1c values should be monitored at each quarterly visit. An international expert committee composed of appointed representatives of the American Diabetes Association, the European Association for the Study of Diabetes, and others, recommended HbA1c assay for the diagnosis of diabetes mellitus in nonpregnant adults.[52] The committee’s recommendation to diagnose diabetes is an HbA1c level of 6.5% or higher, with confirmation from repeat testing (unless clinical symptoms are present and the glucose level is >200 mg/dL). Glucose measurement should remain the choice for diagnosing pregnant women or should be used if HbA1c assay is unavailable. The committee listed the following advantages of HbA1c testing over glucose measurement:

  • Captures long-term glucose exposure

  • Has less biologic variability

  • Does not require fasting or timed samples

  • Is currently used to guide management decisions

Additional concerns

Additional monitoring should be performed as follows:

  • Microalbuminuria and fasting lipid profile - Should be checked yearly

  • Dilated eye examination - Should be done annually

  • Blood pressure evaluation and careful neurologic - Should be performed at each clinic visit

Weight loss, increased physical activity, and better food choices should be encouraged because they improve fasting lipid profile. Growth assessment is important.

 

Metformin (Glucophage, Glumetza, Riomet, Fortamet)

Metformin use frequently results in weight loss and mild improvement of all aspects of the lipid profile. It cannot be used in renal or hepatic insufficiency or decompensated congestive heart failure requiring pharmacologic therapy (due to an increased risk for lactic acidosis).

Metformin can be used as monotherapy or with sulfonylureas, glitazones, or insulin. It reduces hepatic glucose output, may decrease intestinal absorption of glucose, and may increase glucose uptake in peripheral tissues. It is a major drug used in obese patients with type 2 diabetes.

Because of adverse gastrointestinal (GI) effects from metformin, titrate the drug slowly and have patients take the medication during (rather than before) meals. Many patients tolerate metformin best if it is administered in the middle or at the end of the meal. The drug is available in immediate-release (IR) or extended-release (ER) form. Only the IR form has been approved for children.

Tolbutamide

Tolbutamide increases insulin secretion from pancreatic beta cells.

Nateglinide (Starlix)

Nateglinide is an amino acid derivative that stimulates insulin secretion from the pancreas (within 20 minutes of oral administration), which, in turn, reduces blood glucose levels. The drug's action depends on functional beta cells in pancreatic islets. Nateglinide interacts with the adenosine triphosphate (ATP) ̶ sensitive potassium channel on pancreatic beta cells.

Miglitol (Glyset)

Miglitol delays glucose absorption in the small intestine and lowers postprandial hyperglycemia.

Pioglitazone (Actos)

Pioglitazone improves target cell response to insulin without increasing insulin secretion from the pancreas. It decreases hepatic glucose output and increases insulin-dependent glucose use in skeletal muscle and, possibly, in liver and adipose tissue.

Liraglutide (Victoza)

Liraglutide is an incretin mimetic agent that elicits glucagonlike peptide-1 (GLP-1) receptor agonist activity. It activates the GLP-1 receptor by stimulating G-protein in pancreatic beta cells. Liraglutide increases intracellular cyclic adenosine monophosphate (AMP), leading to insulin release in the presence of elevated glucose concentrations. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. The drug has not been studied in combination with insulin.

Pramlintide (Symlin)

Pramlintide is a synthetic analogue of human amylin, a naturally occurring hormone made in pancreatic beta cells. It slows gastric emptying, suppresses postprandial glucagon secretion, and regulates food intake through centrally mediated appetite modulation. The drug is indicated to treat type 1 and type 2 diabetes in combination with insulin. It is administered before mealtime for patients who have not achieved desired glucose control despite optimal insulin therapy. Pramlintide helps to achieve lower blood glucose levels after meals, less fluctuation of blood glucose levels during the day, and improvement of long-term control of glucose levels (ie, HbA1C levels), compared with insulin alone. Less insulin use and a reduction in body weight are also observed.

Saxagliptin (Onglyza)

Saxagliptin blocks DPP-4, which is known to degrade incretin hormones, increasing concentrations of active intact incretin hormones (GLP-1 and GIP). The hormones stimulate insulin release in response to increased blood glucose levels following meals. This action enhances glycemic control. Saxagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes.

Insulin degludec (Tresiba)

Ultra-long-acting insulin that is the only insulin product approved by the FDA to improve glycemic control in pediatric patients aged ≥1 y with type 2 DM. It usually takes 3-4 days for insulin degludec to reach steady state, peak plasma time is 9 h and the duration of action is at least 42 h. It is highly protein bound, and following SC administration, the protein-binding provides a depot effect.

Insulin degludec is produced by a process that includes expression of recombinant DNA in Saccharomyces cerevisiae followed by chemical modification. Insulin degludec differs from human insulin in that the amino acid threonine in position B30 has been omitted and a side-chain consisting of glutamic acid and a C16 fatty acid has been attached.

 

Questions & Answers

Overview

What causes pediatric type 2 diabetes mellitus (DM)?

How is pediatric type 2 diabetes mellitus (DM) characterized?

Which physical findings suggest pediatric type 2 diabetes mellitus (DM)?

What are the indications for pediatric type 2 diabetes mellitus (DM) testing?

What are the recommendations for pediatric type 2 diabetes mellitus (DM) screening?

How are glucose values interpreted in pediatric type 2 diabetes mellitus (DM)?

Which lab results suggest pediatric type 2 diabetes mellitus (DM)?

How is albuminuria tested in pediatric type 2 diabetes mellitus (DM)?

What are the optimal values of fasting lipid profiles in the workup of pediatric type 2 diabetes mellitus (DM)?

What are the glycemic and nonglycemic goals in pediatric type 2 diabetes mellitus (DM) treatment?

How is pediatric type 2 diabetes mellitus (DM) treated?

How is pediatric type 2 diabetes mellitus (DM) monitored?

What is pediatric type 2 diabetes mellitus (DM)?

What are the acute complications of pediatric type 2 diabetes mellitus (DM)?

What are long-term complications of pediatric type 2 diabetes mellitus (DM)?

What causes pediatric type 2 diabetes mellitus (DM)?

What are the risk factors for pediatric type 2 diabetes mellitus (DM)?

What is the prevalence of pediatric type 2 diabetes mellitus (DM) in the US?

What is the global prevalence of pediatric type 2 diabetes mellitus (DM)?

Which patient groups have the highest prevalence of pediatric type 2 diabetes mellitus (DM)?

What is the prognosis of pediatric type 2 diabetes mellitus (DM)?

What are the components of patient education for pediatric type 2 diabetes mellitus (DM)?

What is included in practical skills training for patients with pediatric type 2 diabetes mellitus (DM)?

What should be addressed in ongoing patient education about pediatric type 2 diabetes mellitus (DM)?

Presentation

Which clinical history findings are characteristic of pediatric type 2 diabetes mellitus (DM)?

Which physical findings are characteristic of pediatric type 2 diabetes mellitus (DM)?

DDX

Which conditions are included in the differential diagnoses of pediatric type 2 diabetes mellitus (DM)?

What are the differential diagnoses for Pediatric Type 2 Diabetes Mellitus?

Workup

What are the ADA guidelines for pediatric type 2 diabetes mellitus (DM) screening and testing?

What is the role of plasma glucose testing in the workup of pediatric type 2 diabetes mellitus (DM)?

How is microalbuminuria assessed in pediatric type 2 diabetes mellitus (DM)?

How is dyslipidemia assessed in the workup of pediatric type 2 diabetes mellitus (DM)?

Treatment

What are the AAP treatment guidelines for pediatric type 2 diabetes mellitus (DM)?

What are the glycemic and nonglycemic goals in pediatric type 2 diabetes mellitus (DM) treatment?

When is inpatient care indicated for the treatment of pediatric type 2 diabetes mellitus (DM)?

What increases the risk of pregnancy in pediatric type 2 diabetes mellitus (DM)?

Which dietary modifications are used in the treatment of pediatric type 2 diabetes mellitus (DM)?

Which activity modifications are used in the treatment of pediatric type 2 diabetes mellitus (DM)?

How is pediatric type 2 diabetes mellitus (DM) prevented?

What is the role of medications in the treatment of pediatric type 2 diabetes mellitus (DM)?

What is a proposed management algorithm for pediatric type 2 diabetes mellitus (DM)?

What are the AHA-ASA guidelines for the prevention of stroke in pediatric type 2 diabetes mellitus (DM)?

What is included in the long-term monitoring of pediatric type 2 diabetes mellitus (DM)?

Medications

Which medications in the drug class Antidiabetics, Insulins are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Dipeptidyl peptidase IV (DPP-4) inhibitors are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Amylin analogue are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Glucagon-like Peptide-1 (GlP-1) Receptor Agonists are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Thiazolinediones (glitazones) are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Alpha-glucosidase inhibitors are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Meglitinides are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Sulfonylureas are used in the treatment of Pediatric Type 2 Diabetes Mellitus?

Which medications in the drug class Biguanides are used in the treatment of Pediatric Type 2 Diabetes Mellitus?