Basics
Description
Hyperglycemia, fitting criteria for diabetes, in a setting of insulin resistance with insufficient insulin secretion for given insulin resistance
Epidemiology
- Increased prevalence over past three decades
- Type 2 diabetes mellitus (T2DM) accounts for 15-86% of newly diagnosed cases of diabetes in youth (10-19 years). Wide variation depending on population affected.
- Incidence (per 100,000 person-years, 0-19 years)
- Pima Indians = 330
- African American = 10
- Non-Hispanic whites = 2.8
- Prevalence (per 100,000 youth 10-19 years)
- Pima Indians = 5,100
- African American = 106
- Hispanic = 46
- Non-Hispanic whites = 18
Risk Factors
- Female gender
- Ethnic minorities
- Adolescence (10-19 years)
- Pubertal
- Offspring of mothers with gestational diabetes
- Family history of type 2 diabetes
- History of the following:
- Large for gestational age at birth
- Intrauterine growth retardation
- Impaired fasting glucose
- Fasting glucose 100 mg/dL (5.6 mmol/L)-125 mg/dL (6.9 mmol/L)
- Impaired glucose tolerance
- Based on 2-hour glucose from oral glucose tolerance test (OGTT; see the following) of 140 mg/dL (7.8 mmol/L)-199 mg/dL (11 mmol/L)
Pathophysiology
- Characterized by insulin resistance and beta cell dysfunction
- Insulin resistance
- Major abnormality in youth with T2DM
- A disorder in which tissues (muscle, hepatic, adipose) have a decreased response to insulin, mediated by abnormal phosphorylation of insulin receptor
- Ideally, a compensatory hyperinsulinemia develops to maintain euglycemia.
- In the presence of beta cell dysfunction, inadequate amounts of insulin are secreted to meet demands from insulin resistance.
- This relative deficiency in beta cell function leads to hyperglycemia and diabetes.
Diagnosis
- T2DM usually presents in setting of the following:
- Family history of type 2 diabetes
- Overweight or obesity (BMI ≥85th percentile for age, gender)
- Other abnormalities associated with insulin resistance (i.e., acanthosis nigricans)
- Residual (yet abnormal) beta cell function
- No diabetes autoimmunity
History
- Asymptomatic (most common)
- Polyuria
- Polydipsia
- Weight loss
- Blurry vision
- Increase in nocturia
- Improvement in acanthosis nigricans
- Family history of type 2 diabetes
- Maternal gestational diabetes
- Medications associated with hyperglycemia:
- For example: glucocorticoid, growth hormone, atypical psychotics, tacrolimus
Physical Exam
- Overweight (BMI ≥85th percentile but <95th percentile) or obesity (BMI ≥95th percentile)
- Hypertension
- Acanthosis nigricans
- Vaginal candidiasis
Diagnostic Tests & Interpretation
Lab
- Diagnosis of diabetes mellitus:
- HgbA1c ≥6.5%
- Using NGSP-certified method
- False negatives when increased blood cell turnover is present
- Fasting glucose ≥126 mg/dL (7 mmol/L)
- 2-hour OGTT glucose ≥200 mg/dL (11.1 mmol/L)
- At time 0, give oral glucose 1.75 g/kg (maximum dose 75 g) over 5 minutes.
- At time 120 minutes, measure glucose.
- If asymptomatic, do 2nd OGTT on a subsequent day to confirm.
- Random glucose >200 mg/dL with symptoms of hyperglycemia
- Distinguish type 1 from type 2 diabetes.
- C-peptide or insulin in setting of hyperglycemia
- Normal or elevated in type 2 diabetes
- Low C-peptide or insulin does not rule out type 2 diabetes.
- Diabetes autoimmune panel
- Negative usually in type 2 diabetes
- Pancreatic autoantibodies; insulin, islet cell, IA-2, GAD, ZnT8
- Evaluate for acute complications of diabetic ketoacidosis (DKA) and/or hyperglycemic hyperosmolar state (HHS).
- Check urine for ketones.
- If urine ketones present (in setting of hyperglycemia), check for DKA.
- Venous gas: pH <7.30
- Metabolic panel: HCO3- <15 mEq/L
- If urine ketones negative or low and patient appears ill, check for HHS.
- Serum glucose: >600 mg/dL (33 mmol/L)
- Serum osmolality: >330 mOsm/kg
- Metabolic panel: HCO3- >15 mEq/L
Differential Diagnosis
- Type 1 diabetes
- Atypical diabetes
- Medication-induced diabetes
- Maturity onset diabetes of youth (MODY)
- Monogenic disorders of glucose regulation
- Abnormalities of beta cell function common
- However, youth can be overweight or obese.
- Genetic testing for MODY is available.
- Renal glycosuria
- Stress-induced hyperglycemia
Alert
Treat youth with possible type 2 diabetes with insulin, as if they have type 1 diabetes, until clinical course and laboratory findings prove otherwise.
Treatment
- Treatment will focus on youth presenting with type 2 diabetes who don't have DKA or HHS.
- Goal of treatment is glucose regulation in order to 1) limit hypoglycemia and hyperglycemia and 2) minimize and delay onset of microvascular and macrovascular disease.
Medication
Insulin
- Initiate treatment with insulin unless clinical picture and laboratory studies support type 2 diabetes and not type 1 diabetes.
- If diagnosis is type 2 diabetes, but initial glucose is >250 mg/dL or HgbA1c ≥9%, insulin therapy is still recommended.
- Initiate basal-bolus insulin regimen (may need to individualize)
- Total daily dose 0.5-1.0 unit/kg/day (TDD)
- 40% in long-acting (detemir, glargine) usually given at bedtime
- For meals and snacks, calculate number of carbohydrates to be eaten and cover with short-acting insulin (lispro, aspart, glulisine).
- Calculate carbohydrate coverage: 1 unit of insulin for every X grams of carbohydrates, often start with X = 500/TDD.
- For hyperglycemia prior to mealtimes, give correction doses of short-acting insulin by using the sensitivity factor.
- Insulin sensitivity factor: 1 unit of insulin will drop glucose by X, often start with X = 1800/TDD.
- Correct until goal blood glucose is reached: begin with goal 120-150 mg/dL.
- Insulin regimen outlined above gives increased flexibility and decreased risk of hypoglycemia with at least 4 injections a day.
- When hyperglycemia is improved and diagnostic tests supportive of type 2 diabetes, introduce metformin and attempt insulin wean.
- Insulin regimen needs to be tailored to the patient and family, and often alternative regimens with fewer injections but more rigid eating schedules and higher risk of hypoglycemia are preferred.
- Two injections per day: premixed insulin
- 2/3 of TDD with breakfast
- 1/3 of TDD with dinner
- Three injections per day: split-mixed
- 2/3 of TDD with breakfast (2/3 NPH, 1/3 short-acting)
- 1/9 of TDD with dinner (short-acting)
- 2/9 of TDD at bedtime (NPH)
- Side effect of all insulin regimens is hypoglycemia, especially with increased activity, decreased oral intake, addition of oral antihyperglycemic. Adjust dose to prevent.
Metformin
- Only FDA-approved medication for type 2 diabetes in youth
- First line of therapy for youth with type 2 diabetes with random glucose <250 mg/dL and HgbA1c <9%
- Begin at 500 mg once a day. Increase by 500 mg every 1-2 weeks as tolerated to reach goal of 2,000 mg daily.
- Side effects:
- Short-term: anorexia, flatus, abdominal pain
- Long-term: lactic acidosis (avoid with renal failure, hypoxia, liver disease) and vitamin B12 deficiency
- Stop 48 hours prior to elective surgery or contrast study with dye.
Additional Treatment
Weight management
- Physical activity
- 60 minutes moderate to vigorous activity a day
- Can be split throughout the day
- Start with shorter periods of daily activity and gradually increase to 60-minute goal.
- Treat orthopedic, respiratory issues.
- Individualize plan: walking to formal sports.
- Sedentary activity
- Decrease sedentary activity.
- Limit screen time (handheld devices, computers, television) to <2 hours a day.
- Remove televisions/screens from bedrooms.
- Nutrition
- Healthy eating choices
- Guidelines from Pediatric Weight Management Evidence-based Nutrition Practice Guidelines, Academy of Nutrition and Dietetics
- Surgical intervention (i.e., gastric bypass)
- Rarely, as part of weight loss program
Ongoing Care
Follow-up Recommendations
- Blood glucose monitoring
- Insulin Rx: preprandial, bedtime
- Oral medication: Consider fasting, bedtime.
- Increase when ill, changing dose, concern for low or high glucose.
- Decrease when stable, in good control.
- Clinic visit with HgbA1c every 3 months
- Goal HgbA1c <7% (may need to individualize); modify treatment as needed.
- Recent study suggests adolescents fail metformin monotherapy rapidly. May need to add additional therapy to reach goals
- Address postprandial glucose excursions to possibly limit risk of macrovascular disease.
- Suggestions for modifying treatment regimen:
- Introduce long-acting insulin at night.
- Introduce short-acting insulin at meals.
- Introduce additional oral antihyperglycemic (not FDA-approved, many with concerns for longer term complications; i.e., rosiglitazone).
- Prevention of DKA and HHS by increasing adherence to treatment plan
- Monitor for hypoglycemia and modify regimens to decrease episodes.
- Little is known regarding disease course in adolescents with T2DM. The SEARCH and TODAY studies have increased our knowledge of prevalence of abnormalities and raised concern for progression of microvascular and risks for macrovascular disease early in course of T2DM.
- Microvascular disease has been noted at presentation or early in course of T2DM.
- Recommendations based on adults (in addition to improving glucose control)
- Retinopathy
- Examination at diagnosis, then annually
- Tx includes laser photocoagulation
- Microalbuminuria
- Measure at diagnosis, then annually.
- Abnormal: random: 30-200 mg/kg
- Perform timed overnight collection. Need 2/3 abnormal samples: 20-199 mcg/min.
- Treat with ACE inhibitor until microalbumin excretion is normalized.
- Peripheral neuropathy
- Examination at diagnosis, then annually
- Changes in sensation in feet, leg
- Autonomic neuropathy
- Assess at diagnosis, then annually.
- May present as tachycardia, orthostasis, gastroparesis
- Cardiovascular disease
- Optimize therapy for hypertension, dyslipidemia, smoking cessation.
Issues For Referral
- Other disorders are commonly associated with type 2 diabetes and may contribute to development of complications.
- If present, referral/treatment should occur:
- Hypertension
- Dyslipidemia
- Depression
- Obstructive sleep apnea
- Nonalcoholic fatty liver disease
- Orthopedic abnormalities (i.e., SCFE)
- Polycystic ovary syndrome
- Dental abnormalities
Additional Reading
- American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care. 2014;37(Suppl 1):S14-S80. doi:10.2337/dc14-S014. [View Abstract]
- Copeland KC, Silverstein J, Moore KR, et al. Management of newly diagnosed type 2 diabetes mellitus (T2DM) in children and adolescents. Pediatrics. 2013;131(5):364-382. doi:10.1542/peds.2012-3494. [View Abstract]
- Fazeli Farsani S, van der Aa MP, van der Vorst MM, et al. Global trends in the incidence and prevalence of type 2 diabetes in children and adolescents: a systematic review and evaluation of methodological approaches. Diabetologia. 2013;56(7):1471-1488. doi:10.1007/s00125-013-2915-z. [View Abstract]
- Springer SC, Silverstein J, Copeland K, et al. Management of type 2 diabetes mellitus in children and adolescents. Pediatrics. 2013;131(2):e648-e663. doi:10.1542/peds.2012-3496. [View Abstract]
- TODAY Study Group, Zeitler P, Hirst K, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247-2256. [View Abstract]
- Writing Group for the SEARCH for Diabetes in Youth Study Group, Dabelea D, Bell RA, et al. Incidence of diabetes in youth in the United States. JAMA. 2007;297(24):2716-2724. [View Abstract]
Codes
ICD09
- 250.00 Diabetes mellitus without mention of complication, type II or unspecified type, not stated as uncontrolled
- V18.0 Family history of diabetes mellitus
- 250.70 Diabetes with peripheral circulatory disorders, type II or unspecified type, not stated as uncontrolled
- 250.50 Diabetes with ophthalmic manifestations, type II or unspecified type, not stated as uncontrolled
- 250.60 Diabetes with neurological manifestations, type II or unspecified type, not stated as uncontrolled
ICD10
- E11.9 Type 2 diabetes mellitus without complications
- Z83.3 Family history of diabetes mellitus
- E11.51 Type 2 diabetes w diabetic peripheral angiopath w/o gangrene
- E11.319 Type 2 diabetes mellitus with unspecified diabetic retinopathy without macular edema
- E11.40 Type 2 diabetes mellitus with diabetic neuropathy, unsp
ICD10
- 44054006 Diabetes mellitus type 2 (disorder)
- 430679000 family history of diabetes mellitus type 2 (situation)
- 427134009 Small vessel disease due to type 2 diabetes mellitus (disorder)
- 422034002 Diabetic retinopathy associated with type II diabetes mellitus (disorder)
- 1511000119107 Diabetic peripheral neuropathy associated with type II diabetes mellitus (disorder)
FAQ
- Q: What are some of the challenges of follow-up care in youth with type 2 diabetes?
- A: Possible challenges include the following:
- Competing financial/time constraints
- Adolescent age
- Lack of symptoms from hyperglycemia and early complications of hyperglycemia
- Lack of social support networks
- Pervasiveness of type 2 diabetes in families