Optimizing combination therapy for type 2 diabetes in adolescents and adults: A case-based approach
TABLE 1 provides criteria for screening for type 2 diabetes in children. The adolescent in the case presented has several risk factors for type 2 diabetes, including obesity, a positive family history, Hispanic descent, and acanthosis nigricans. To more definitively diagnose type 2 diabetes, additional laboratory tests are needed, including assessment of blood glucose and insulin production, as well as the presence of autoantibodies.
TABLE 1
Screening recommendations for type 2 diabetes in children
| Testing for type 2 diabetes is recommended every 2 years at onset of puberty or aged >10 years (whichever comes first) if the child* |
|
| *Clinical judgment should be used to test for diabetes in high-risk patients who do not meet these criteria. |
| †Overweight is defined as BMI >85th percentile for age and sex, weight for height >85th percentile, or weight >120% of ideal for height. |
| Copyright © 2004 American Diabetes Association from Diabetes Care,2004;27(suppl 1):S15-S35. Reprinted with permission. |
CASE 1 Laboratory assessment
The patient has a fasting plasma glucose (FPG) level of 215 mg/dL. β-Cell or insulin autoantibodies are not detected. He has a normal-to-high fasting C-peptide level, microalbuminuria, and a serum creatinine level of 0.8 mg/dL. His lipid panel results include: total cholesterol, 234 mg/dL; low-density lipoprotein (LDL) cholesterol, 159 mg/dL; high-density lipoprotein (HDL) cholesterol, 45 mg/dL; and triglycerides, 150 mg/dL.
A comparison of the typical presentation and laboratory findings in pediatric type 1 and type 2 diabetes is listed in TABLE 2. This information underscores that there is significant overlap between the 2 disease classifications.
The laboratory results for this patient confirm a diagnosis of type 2 diabetes. C peptide is a marker of endogenous insulin production and is particularly helpful in the classification of diabetes when it is high, which is indicative of type 2 diabetes. However, it should be noted that a finding of low C-peptide levels does not rule out type 2 diabetes since there is a possibility that glucose toxicity is temporarily limiting insulin production. Indeed, in such a case, insulin therapy can be initiated to establish glycemic control and promote endogenous insulin production by reducing glucose toxicity. Similarly, although the absence of pancreatic β-cells and insulin autoantibodies is consistent with a diagnosis of type 2 diabetes, the presence of such antibodies does not completely rule out type 2 diabetes.19
Like many patients with type 2 diabetes, the current patient exhibits a cluster of CVD risk factors that characterize the metabolic syndrome, including dyslipidemia (elevated total cholesterol, LDL cholesterol, triglyceride levels, and low HDL cholesterol levels), hypertension, glucose intolerance, hyperinsulinemia, and central or abdominal obesity. This is not surprising as an estimated 30% of overweight adolescents, defined as those with BMI at or above the 95th percentile, meet the criteria for metabolic syndrome.14
TABLE 2
Classification of type 1 and type 2 diabetes in pediatric patients
| TYPE 1 DIABETES | TYPE 2 DIABETES | |
|---|---|---|
| Age | Throughout childhood | Pubertal |
| Onset | Acute, severe | Mild to severe, often insidious |
| Insulin secretion | Very low | Variable |
| C-peptide level | Absent | Variable |
| Insulin sensitivity* | Normal | Decreased |
| Insulin dependence† | Permanent | No |
| Genetics | Polygenic | Polygenic |
| Race/ethnic distribution | All (low frequency in Asians) | African American, Hispanic, Asian, American Indian, Pacific Islanders |
| Association | ||
| Obesity | No | Yes, strong |
| Acanthosis nigricans | No | Yes |
| Autoimmunity | Yes | No |
| Presence of autoantibodies | Yes | No‡ |
| *Insulin sensitivity is given as a pathogenic factor. | ||
| † In the absence of acute illness or other stress. | ||
| ‡ Although autoimmunity is not a cause of type 2 diabetes, diabetic autoimmune markers can be present at times and should not be used to rule out a diagnosis of type 2 diabetes in children and adolescents.19 | ||
| Copyright © 2004 American Diabetes Association from Diabetes Care, 1999;22:345-354. Reprinted with permission. | ||
CASE 1 Initial therapy
The patient is provided with education on lifestyle modifications to reduce weight and obtain better control of glucose, lipids, and BP. Instructions include ways to improve his eating habits and to increase his physical activity when away from the football field, such as limiting time spent watching TV and playing video games and increasing exercise time and effort. The patient also is instructed on self-monitoring for blood glucose (SMBG) and is given a referral to an ophthalmologist to determine whether there is any baseline retinopathy.
At his 3-month follow-up, the patient’s A1C is 8.7%, and his weight has not changed. At this point, lifestyle modifications are reinforced, and pharmacotherapy with extended-release metformin is initiated and titrated to 2,000 mg/d.
Typically, the first approach to managing type 2 diabetes involves dietary changes and instituting an exercise program to reduce weight and to improve insulin sensitivity. This was the approach used in the patient described above. However, as is frequently the case, lifestyle modifications by themselves are insufficient to meet the American Diabetes Association (ADA) or American Association of Clinical Endocrinologists targets for glycemic control (A1C <7% and <6.5%, respectively).20,21 It is important to note here that the ADA does recommend less stringent glycemic control guidelines in very young children (ie, those aged less than 13 years).16 As is the case for adults with diabetes, pharmacologic therapies typically are needed in addition to lifestyle changes to lower elevated blood glucose levels. However, unlike the situation with adults, the list of drugs approved by the Food and Drug Administration for use in pediatric patients is limited (ie, currently only metformin and insulin preparations are approved for pediatric use).
