(Pediatr Diabetes 2009;10(Suppl 12):1: ISPAD Clinical Practice Consensus Guidelines 2009 Compendium)
Epidemiology
• Western countries: T1DM >90% of childhood/adolescent DM; incidence greatest in Finland > Sardinia > Canada > Sweden > UK > USA
• Onset bimodal (1st peak at 4–6 yo & 2nd at early puberty) & ↑ in winter
• No recognizable pattern of inheritance though familial aggregation ∼10%; 2–3× more common in offspring of diabetic men than women
• Concordance rates for monozygotic twins 30–50%; genetic factors: HLA DR 3,
4—and as yet unknown environmental triggers
Clinical Manifestations
• Asymptomatic incidental hyperglycemia/glycosuria or
• Classic symptoms: Polyuria and polydipsia (70%), weight loss (34%) often w/ inc in appetite (polyphagia), lethargy (16%), and nocturnal enuresis
• Diabetic ketoacidosis (DKA): Classic sx +/− vomiting and abdominal pain, fruity breath (acetone), Kussmaul respirations, obtundation, coma
• If identified thru antibody screening and f/u (DPT1 trial) approx 70% asymptomatic but DKA initial presentation 15–70% in Europe and NA
• DKA is freq in very young children, in families w/o FHx of diabetes, and lower socioeconomic status
• Dehydration: Mild to severe, because of osmotic diuresis
• Visual changes: 2/2 osmotic shifts in lens or cataracts if prolonged hyperglycemia
• Candidal infections (more common in younger children)
Epidemiology (Pediatrics 2004;113:e133)
• DKA as 1st presentation of DM1 more often in pts <4 yo, w/o a 1st-degree relative w/ DM1, and of lower socioeconomic status
• 25% of new onset diabetes in children presents as DKA
• Incidence of 1–10% per patient per yr in established DM1
• Risk factors for recurrent DKA: Poor control, previous episodes of DKA, peripubertal or adolescent, psychiatric disorders, lower SES, insulin not administered by responsible adult, pump failure, inadequate insulin during intercurrent illness
Diagnostic Studies
• Hemoglobin A1c: Glycated Hgb; good marker of serum glucose over 2–3 mo (nml RBC lifespan 100–120 d)
• Accuracy affected by hemolysis, RBC turnover, and hemoglobinopathies (if hemoglobinopathy, measure total glycated Hgb, not HbA1C)
• Anti-islet cell Ab (ICA), anti-insulin Ab (IAA; check before admin insulin), anti-IA2 (islet antigen 2, aka ICA512) Ab, anti-GAD (glutamic acid decarboxylase, aka GAD65) Ab
• Consider eval for other autoimmune conditions (ISPAD)
• Autoimmune thyroid dz (antithyroid peroxidase Ab, antithyroglobulin Ab), in up to 18% of newly dx’d DMI pts. Check TSH/free T4
• Celiac sprue (anti-TTG Ab), + up to 5% of newly dx’d DMI
• Also consider adrenal insufficiency, vitiligo, & autoimmune poly-endocrinopathies
Monitoring (Diabetes Care 2005;28:186)
• Blood glucose checked before meals and at bedtime. Consider testing at MN, at
2–4 am, and after meals shortly after dx or when altering regimens
• HgbA1c every 3 mo (see age specific goals, below)
• Dilated retinal exam every year after 10 yr
• Fasting lipid panel at diagnosis and then q5yr if normal or yearly after 10 yr
• TSH, free T4 yearly; anti-TPO antibodies, antithyroglobulin antibodies initially
• Celiac screening every 2 yr
• Urine microalbumin: Creatinine ratio yearly after 10 yr
Management
• Insulin regimen requires estimation of total daily dose (TDD) of insulin
• Start dose btw 0.3 and 0.6 U/kg/d; prepubertal pts may need less (0.25–0.5 U/kg/d); pubertal pts and those who present in DKA may require more (0.5–1 U/kg/d)
• Onset and action of insulins
• Conventional insulin Rx (2–3 injections per d)
• NPH at least bid (before breakfast w/ 2nd dose either before dinner or bedtime), w/ rapid-acting or short-acting (“regular”) insulin 2–3×/d
• Requires fixed schedule of eating & insulin dosing and fixed amt of carbs at meals
• Basal-bolus (4+ injections/d) (Diabet Med 2006;23:285)
• Assoc w/ improved HgbA1c, dec gluc fluctuations, and dec hypoglycemia
• Long-acting 1–2×/d plus rapid-acting insulin w/ meals
• 50% of TDD is long acting
• 50% of TDD rapid acting—dose based on blood sugar and carb content
• Estimate of correction factor (CF): 1500/TDD gives amt by which serum glucose expected to dec, in mg/dL for 1 unit of rapid-acting insulin
• Estimating insulin: Carb ratio (CR); 500/TDD gives # of grams of carbs that are covered by 1 unit of rapid-acting insulin (∼1/3 CF)
• Insulin pump: Use rapid-acting insulin for basal infusion and bolus corrections
• Assoc w/ less hypoglycemia, improved HgbA1c compared with NPH-based regimens, and improvements in quality of life scales (Diabetes Care 2008;31:S140)
• Education regarding symptoms of hypoglycemia is very important (<70 mg/dL)
Treatment Goals (ADA): (Diabetes Care 2005;28:186)
• <6 yo; plasma glucose before meals 100–189; bedtime/overnight 110–200; A1c < 8.5% but >7.5%; high risk and vulnerable to hypoglycemia
• 6–12 yo; before meals 90–180; bedtime/overnight 100–180; A1c < 8%; hypoglycemia risk vs. relatively low risk of complications prior to puberty
• 13–19 yo; before meals 90–130; bedtime/overnight 90–150; A1c < 7.5%; generally w/ lower risk of hypoglycemia; if no excessive hypoglycemia, can aim for <7%
Complications
• Hypoglycemia (<70 mg/dL); Rx w/ PO glucose (15 g carbs = 4 oz juice = 1 tblspn sugar, glucose tablets, or IV dextrose bolus, consider 0.5–1 mg SC/IV glucagon if unable to swallow. Smaller doses of glucagon [20–150 mcg] minibolus therapy) every 1–2 hr can be useful if unable to take PO (J Paediatr Child Health 2006;42:108)
• Microvascular complications (retinopathy, neuropathy, renal disease)
• Macrovascular complications (coronary vascular disease, peripheral vascular disease)
• DCCT: Significant correlation btw HgbA1c and risk of both microvascular and macrovascular complications (N Engl J Med 2000;342:381)