Fasting glucose ≥126 mg/dL, 2-hr OGTT (oral glucose tolerance test) glucose ≥200 mg/dL, or random glucose ≥200 mg/dL in the presence of symptoms. In absense of symptoms, level needs to be repeated on diff day.

Type 1 diabetes: Autoimmune disorder w/ T cell-mediated destruction of pancreatic islet cells, causing insulin deficiency. + pancreatic autoantibodies. Rx w/ insulin.

Type 2 diabetes: Peripheral resistance to insulin action and variably dysregulated/diminished insulin secretion. Rx w/ oral hypoglycemic agents and/or insulin.

Maturity-onset diabetes of the young (MODY): Heterogeneous group of genetic disorders caused by mutations in beta cell genes.

Mitochondrial diabetes: Mitoc DNA mutations w/ hyperglycemia and other features, (e.g., Kearns-Sayre syndrome [diabetes, ophthalmoplegia, retinal degeneration, cardiomyopathy]), maternally-inherited diabetes and deafness syndrome (MIDD).

Prevalence in the U.S. is 1 in 400–500; increased in northern latitudes.

Age of onset has bimodal distribution (1st peak at 4–6 yo & 2nd at early puberty)

FHx of type 1 diabetes (1° relative) in 15% of patients

Concordance rates for monozygotic twins 21%–70%, implies roles for genetic factors (HLA genotype) and environmental triggers (possibly viral infxn, diet, toxins)

May be asymp and just incidental hyperglycemia on blood work

Classic symptoms: Polyuria and polydipsia (70%), weight loss (34%) often w/ inc appetite (polyphagia), lethargy (16%), and nocturnal enuresis

Diabetic ketoacidosis (DKA): Classic sx +/- vomiting and abdominal pain, fruity breath (ketones), Kussmaul respirations, obtundation, coma.

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)

Hemoglobin A1c: Glycosylated Hgb; good marker of serum glucose conc over 2–3 mo

Anti-islet cell Ab (ICA), anti-insulin Ab (IAA; ideally obtained before admin insulin), anti-IA2 (islet antigen 2, a.k.a. ICA512) Ab, anti-GAD (glutamic acid decarboxylase, a.k.a. GAD65) Ab

Consider eval for other autoimmune conditions (Diabetes Care 2001;24:27)

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 age 10 yr

Fasting lipid panel at diagnosis and then q5 yr if normal

TSH, free T₄ yearly; anti-TPO antibodies, anti-thyroglobulin antibodies initially

Celiac screening every 1–2 yr

Urine microalbumin: Creatinine ratio yearly after age 10 yr

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 (0.5–0.75 U/kg/d)

Onset and action of insulins:

Conventional insulin Rx (2–3 injections per d)

Basal-Bolus (4+ injections/d) (Diabet Med 2006;23:285)

Education regarding symptoms of hypoglyecemia is very important

Hypoglycemia; Rx w/ PO glucose or IV dextrose bolus, consider 0.5–1 mg SC/IV glucagon

Microvascular complications (retinopathy, neuropathy, renal disease)

Macrovascular complications (coronary vascular disease, peripheral vascular disease)

U.S. prevalence ↑ing; past 3% new cases DM, now 15%–45% depending on location.

STOPP-T2D trial: ∼50% middle-school students w/ ↑BMI (≥85 percentile), 40% w/ fasting glucose ≥100 mg/dL, (only 0.4% >125 mg/dL, and 1/3 w/ hyperinsulinism w/ fasting insulin ≥30 μU/mL) and thus prediabetes. (Diabetes Care 2006;29:212)

At dx, screen for proteinuria/microalbuminuria, dilated funduscopic exam by ophtho.

Multi studies, 11%–25% of pts p/w DKA, more w/ ketonuria. (See section on DKA)

Hyperglycemic hyperosmolar state (glucose >600 mg/dL, osmolality >330 mOsm/L, mild acidosis w/ bicarbonate >15 mmol/L and mild ketonuria ≤15 mg/dL) 2/2 nonadherence to Rx, meds, and stresses (infections, substance abuse, chronic disease).

Microalbuminuria and risk of AMI ↑ for pts w/ DM2 dx’d at younger ages.

HTN, dyslipidemia, retinopathy, nonalcoholic fatty liver dz, and neuropathy.

Poor glycemic control (by HgbA1c) & HTN predictive of subseq complications.

Complications progress more rapidly in kids and adolescents w/ DM2 than w/ DM1.

Lifestyle Δ, diet modification, weight mgmt, exercise effective, adherence difficult.

Oral hypoglycemics; metformin (FDA approved). Dose can be titrated up slowly to avoid common side effects (headache, nausea).

Eventually may need initiation of insulin therapy

Surveillance as indicated above.

↓ effective circulating insulin and ↑ counterregulatory hormones (glucagon, epinephrine) leading to hyperglycemia and hyperosmolarity

Lipolysis leads to ketonemia and metabolic acidosis

Hyperglycemia and acidosis lead to osmotic diuresis, dehydration, electrolyte loss

Severity: Mild w/ venous pH <7.30, bicarbonate <15 mmol/L, moderate w/ venous pH <7.2, bicarbonate <10, severe w/ venous pH <7.1, bicarbonate <5

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 1%–10% per patient per yr in established DM1

Risk factors: 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

Confirm dx and determine cause (evidence of infection; recurrent DKA, insulin omission, failure to follow sick day/pump failure mgmt guidelines).

Exam: Weight (assess dehydration), fruity breath, acanthosis nigricans (suggests insulin resistance and DM2; may need higher insulin doses)

Assess severity of dehydration (UOP not reliable indicator of hydration in hyperosmolar states given osmotic diuresis); see FEN chapter

Level of consciousness (Glasgow coma scale)

Headache or focal neurologic signs (suggests cerebral edema)

Labs: Blood gas, serum or plasma glucose (not just D-stick), lytes, BUN/Cr, Ca, Mg, Phos, CBC (↑ WBC can be 2/2 stress), HgbA1c, U/A (ketones), consider lactate if severe acidosis or not responding to insulin.

Assess for infectious trigger (blood, urine, and throat cx; consider CXR)

Fluids: Administer 10–20 cc/kg NS IV over 1–2 hr; repeat as necessary

Insulin: IV fluids can normalize hyperglycemia, insulin therapy essential for correcting acidosis (counteracts lipolysis and ketogenesis)

Monitoring: Initially q1h (more freq as needed) VS, neuro exam (cerebral edema; HA, vomiting, bradycardia, HTN, dec O₂ sat, ΔMS, posturing, abn pupil resp, CN palsies), strict I’s and O’s, gases. (Check cap gases against VBG; cap gas inaccurate w/ poor periph perfusion, acidemia, extreme hyperglycemia.) Q1h D-sticks

Calculations: Anion gap = Na – (Cl + HCO₃); normal is 12 ± 2 mmol/L

Potassium: Total intracellular stores depleted but hyperkalemia 2/2 extracellular shift. Replete w/ 1/2 KPhos & 1/2 KCI

Phosphate: Total body stores ↓. Rx hypophos if severe. Rx may result in HypoCa.

Acid-base status: Fluid and insulin replacement should treat metabolic acidosis.

Mortality from DKA is 0.15% in the U.S.

0.5–1% of episodes of DKA c/b cerebral edema; mortality risk of 20–25%.

Electrolyte abnormalities like hypokalemia and hyperkalemia also occur

Please see Neurology chapter section on treatment of cerebral edema

Earlier dx, pt, family, and community education, responsible adults administering insulin, establishing comprehensive treatment networks.

Low serum glu (<45) + sx and resolution of sx after administration of glucose

Sx’s: Perspiration, tachycardia, pallor, paresthesia, tremor, weak, N/V

Nml fall in glucose → ↓ insulin secretion and ↑ counterregulatory hormones

Presence of insulin inhibits adipose tissue breakdown → no ketones

Neonatal: Prematurity (limited stores), infant of diabetic mother, PPHN

Increased glucose use: Hyperthermia, polycythemia, sepsis, hyperinsulinemia

Decreased glycogenolysis, gluconeogenesis, use of alternative fuels