DEFINITION
- Chronic hyperglycemia as a result of inability of the pancreatic beta cells to secrete the amount of insulin the organism needs.
EPIDEMIOLOGY
- Prevalence 8.5% in >18years = 422 M (WHO) in 2014.
- 90% type 2 diabetes, 5-10% type 1 diabetes, <5% other types.
ETIOLOGY
- Type 1 diabetes: (post) destruction of pancreatic islet beta cells:
- 1A: autoimmune, circulating GAD, IA2, Zn8T Ab. There might be a subtype -LADA-: clinically type 2 diabetes with +Ab. Genetically heterogeneous with type 1 traits (HLAQB1) and type 2 traits (TRF7L2).
- 1b: non-autoinmmune
- Type 2 diabetes: (post) heterogeneous etiology where insulin-resistance is mixed to partial beta cell failure.
- Insulin secretion genetic defects:
- MODY. The most common genetic diabetes, 2-5%. Diabetes diagnosed <25y secondary to mutations in genes related to insulin secretion:
- HNF4a (MODY1): 10%. Unclear mechanism. Progressive. Prone to complications.
- GK (MODY2): 25-30%. Stable, mild, diet alone.
- HNF1a (MODY3): 50-65%. ↓ glucose renal threshold → glucosuria precedes diabetes. Unclear mechanism. Progressive. Sensitive to SU. Prone to complications.
- IPF (MODY4).
- HNF4b (MODY5): kidney dysplasia and cysts, genital malformations.
- Neuro D1 (MODY6).
- Other, less frequent.
- Non-mody beta cell defects (rare):
- SUR1 defects: hypos in childhood, diabetes when adult.
- Proinsulin-insulin conversion defects.
- Mutant insulin.
- Mitochondrial DNA defects: MIDD: diabetes and deafness with onset 30-40y.
- Wolfram (DIDMOAD): WFS1 gen defect (wolframin): DI, DM, optic atrophy and deafness. Very rare.
- Defects in insulin action:
- Genetic:
- Leprechaunism
- Rabson Mendenhall
- Type A IR (receptor defects)
- Lipodystrophies
- Secondary:
- Obesity
- Type B IR (Ab against IR)
- Other: stress, drugs, pregnancy, inactivity.
- Pancreatic diseases.
- Cystic fibrosis
- Hemochromatosis
- Chronic pancreatitis
- Fibrocalculous diabetes
- Genetic defects of pancreas development: Carboxyl Ester Lipase (CEL) defect.
- Endocrinopathies:
- Cushing
- Pheochromocytoma
- Acromegaly
- Glucagonoma
- Somatostatinoma
- Drug induced diabetes
- Viral induced diabetes
- Gestational diabetes
- Uncommon immune mediated diabetes:
- Stiff man syndrome (GAD Ab)
- Ab against insulin receptor.
CLINICAL PRESENTATION
- Asymptomatic if glycemia <kidney threshold
- Classical symptoms: polyuria, polydipsia, weight loss, blurred vision when glycemia > threshold, about 180 mg/dL.
- Ketosis and DKA (post) when not enough insulin to control lipolysis: nausea, vomiting, abdominal pain.
- Hiperosmolar hyperglycemic state (HHS) (post) when polyuria not compensated by drinking in fragile patient.
- Diabetic mycro- or macrovascular complication in longstanding undiagnosed diabetes.
DIAGNOSIS
- Percent undiagnosed and time from onset to diagnosis:
- Negligible if important insulin deficiency like type 1 (particularly in children), or pancreatectomy
- Variable in partial ID (asymptomatic) like type 2. Depends on screening, up to 50%. Unknown time to diagnosis, might be years.
- Diagnostic workup:
- Biochemistry, some of these:
- two of these in same or different samples: fasting glycemia >=126 mg/dL, HbA1c >6,5%, any glycemia >200 mg/dL, 2h 75g-OGTT >200 mg/dL
- Classic symptoms or DKA or HHS + glycemia >200 mg/dL
- DD: before biochemistry: syndromes of polyuria-polydipsia: diabetes insipidus, other.
HEALTH IMPACT
- Mortality:↑ depending on hyperglycemia degree and time
- Morbidity:
- Microangiopathy, small vessel specific diabetic complications, depend on degree and time of hyperglycemia:
- Retinopathy (post), may lead to blindness
- Nephropathy (post), may progress to ESRD and ↑mortality.
- Neuropathy (post).
- Macroangiopathy (atherosclerosis), unspecific large vessel disease, depend on hyperglycemia and other CVRF (post)
- Estimated morbidity in undiagnosed cases:
- ↑mortality mostly by macroangiopathy and CKD
- ↑morbidity by macro- and microangiopathy
MANAGEMENT
- Post
