Diabetology

primary diabetes is classified into

primary diabetes is classified into

type 1 - immune patho, severe insulin deficiency

type 2 - insulin resistance + insulin deficiency

secondary diabetes can be subdivided into

• secondary to genetic defects, exocrine pancreatic disease, endocrine disease, drugs + chemicals, infections

• uncommon forms of immune-mediated dm

type 1 dm is subdivided into

type 1a (immune mediated), type 1b (non-immune mediated)

_____ belongs to a family of immune-mediated organ-specific diseases, including autoimmune thyroid disease, celiac, Addison and pernicious anemia

type 1 dm

pathology type 1 dm

autoatb against pancreatic islet parts → asymptomatic loss b cell secretion → insulin treatment → honeymoon period (recovery insulin for few months, stop treatment)

in which dm is weight loss present + seasonal onset + ketonuria + c-peptide dissapears

1

age of the types of dm (1,2,monogenic,secondary)

1 - young

2 - old

monogenic - neonates - teen

secondary - old

which types dm have weeks/months symptom duration

weeks - 1, secondary

months - 2, monogenic

hereditary pattern type 1 dm

hla dr3 or dr4

etiologies t2dm

genetic susceptibility, ageing, fetal origins of dm (poor nutrition early), obesity, lifestyle

patho t2dm

• impaired ability insulin to inhibit glucose output, stimulate glucose uptake and suppress lipolysis

• deficiency insulin (depleted b-cells)

• increased glucagon

• upregulated SGLT2 → increased glucose reabsorption in kidney

monogenic dm cause

single gene mutation affecting b-cell fxn

_______ should be considered in ppl presenting w/ early-onset dm associated w/ affected parent

monogenic dm

predominance monogenic dm

neonates (esp ones with neuro features)

acute presentation triad of dm

polyuria

thirst and polydipsia

weight loss

complications as the presenting feature of dm

staph skin infections, retinopathy, polyneuropathy, a. disease

physical exam at diagnosis of dm

weight loss, dehydration, breath smells of ketones, acanthosis nigricans, htn in dm2

how can dm be diagnosed

fpg, random glucose or 2h OGTT

_____ is an integrated measure of glucose conc over weeks and is also used to guide treatment decisions

glycated hb

how to diagnose dm if absence of clear symptoms

2 abnormal glucose of glycated hb tests needed

individuals with IGT have what risk

risk cardiovasc disease (not of microvasc complications)

impaired glucose tolerance can only be diagnosed with what

glucose tolerance test

when to test c-peptide

ppl w/ duration of dm longer than 5y

how to prevent t2dm

lose weight, reduce fats, increased fiber, physical activity

fourfold aims dm care and management

• prevention dm er

• treatment hyperglycemic symptoms

• minimization long-term complications

• avoidance iatrogenic se (hypoglycemia)

____’s actios tend to persist after meals, predisposing to hypogylcemia

short acting insulins

_______ enter and sisappear from circ. more rapidly than soluble insulin

insulin analogues

insulin glargine, detemir and degludec

long acting insulin

_______ reduce hypoglycemia, particularly at night

long acting insulin analogues

basal-bolus regimen

for t1dm → administration of short (before meal)+ long (1-2/day) acting insulin

twice-daily mixed insulin regimen

mixture short + long acting insulin injected before breakfast + evening meal - common in t2dm

disadvantage twice-daily mixed insulin regimen

increased risk hypoglycemia (@ lunchtime)

basal-only and basal-plus insulin regimens are for which dm

t2dm

how is insulin admninistered

subcutaneously by intermittent injection or insulin pumps @abd wall, thigh, butt, upper outer arms

disadvantages to pump therapy

skin infection, risk ketoacidosis

lipohypertrophy

occur after overuse single injection site w/ insulin

lipoatrophy

due to IgG immune compexes against insulin

most common side effect of insulin therapy (+ major limitation to what can be achieved w/ insulin treatment)

hypoglycemia

hypoglycemia is more common in which dm

t1dm

times of greatest risk of ______ are before meals, at night and after exercise

hypoglycemia

symptoms hypoglycemia

• autonomic (from activation of it) - first to appear. sweating, paresthesia

• neuroglycopenic - slurring, drowsy, loss warning w/ recurrent hypoglycemia

management of hypoglycemia

immediate oral glucose

im/iv glucose if confusion or coma

biguanides (metformin) moa + effects

activation AMP kinase → reduced gluconeogenesis + increased insulin sensitivity

• suppresses appetite + reduction cardiovasc events

clinical use biguanides (metformin)

t2dm

adverse effects metformin

git

CO metformin

renal impairment, cardiac + hepatic failure

sulphonylureas moa

act on b cell to induce insulin secretion

clinical use sulphonylureas

second to metformin for t2dm, or in combo

adverse effects sulphonylureas

weight gain, hypoglycemia

meglitinides (postprandial insulin releasers) moa

close k+-atp channel in b cells (like sulphonylureas), short duration of action for restore post prandially

clinical use meglitinides

ppl w/ post-prandial hyperglycemia w/ normal fasting glucose levels, in older frail ppl

adverse effects meglitinides

hypoglycemia, weight gain

glitazones moa

reduce insulin resistance by interaction w/ PPAR-gamma (mainly found in fat cells)

glitazones

mono or combo, in ppl w/ fatty liver disease as comorbidity

adverse effects glitazones

weight gain, HF, anemia, osteoporosis

gliptins moa

inhibit DPP4 → prevents inactivation GLP1 → increased insulin secretion, reduced glucagon secretion

adverse effects gliptins

nausea, acute pancreatitis, HF

SGLT2 i (‘flozins’) moa

lower renal threshold for glucose → increased glucose excretion, weight loss

• reduce risk cardiovasc events

SGLT2 i (‘flozins’) clinical use

usually combo, in t2dm, in t1dm as adjunctive therapy to insulin

SGLT2 i (‘flozins’) adverse effects

genital candidiasis, dehydration, dka, fournier’s gangrene, lower limb amputation

a-glucosidase i (acarbose) moa

prevent a-glucosidase from breaking down disaccharides → lowered postprandial glucose

adverse effects a-glucosidase i

git (flatulence, bloat, diarrhea)

quick-release bromocriptine method of use

administered at daybreak as mono or combo

_________ is a bile acid-binding resin that lowers cholesterol and can reduce blood glucose conc

colesevalam

GLP-1 r agonists moa

enhance incretin effect by activating glp-1 r, reduce appetite → weight loss, protect heart

clinical use glp-1 r agonists

injection, combo, for obese

DDI glp-1 r agonists

DPP4i

adverse effects + CO glp1 r agonists

git

pancreatitis

amylin analogues

injectable, in t1/2dm, suppresses postprandial glucagon secretion + increases satiety

treatment for patient w/ atherosclerotic cardiovasc disease and/or obesity

glp1 r agonist or sglt2 i

treatment for patient w/ hf or chronic kidney disease

sglt2 i

_______ may be used if there is a need to avoid hypoglycemia

DPP4i and glitazones

self monitoring of cap. blood glucose is recommended for

everyone treated w/ insulin, ppl w/ diet or tablet treated t2dm

_______ have 3 parts: sensor that sits under skin, transmitter attached to sensor and display device

continuous glucose monitoring

continuous glucose monitoring is recommended for

t1dm who have hypoglycemia or persistent hyperglycemia despite frequent cap glucose monitoring

what to do if patient feels hypoglycemic and continuous glucose monitoring levels are changing rapidly (could show normal)

test cap glucose

________ is a measure of an individuals average blood glucose conc over previous 6-8w

glycated hb

islet transplantation

islets injected to portal v. and seed into liver, for t1dm who have hypoglycemia and glucose variability

whole-pancreas transplantation clinical indication

in t1dm and eskd

dka is usually seen in the following circumstances

previously undiagnosed dm, interruption insulin, stress intercurrent illness and infection

ketonuria

ketones in urine, normal in fasting or t1dm

dka

metabolic er in which hyperglycemia associated w. metabolic acidosis due to raised ketone levels

lactic acidosis is associated with which therapy

biguanides

patho ketoacidosis

• uncontrolled catabolism + insulin deficiency and elevated counter-regulatory hormones → hyperglycemia → osmotic diuresis + dehydration

• uncontrolled lipolysis in adipose

• uncontrolled ketogenesis in liver

clinical features ketoacidosis

prostration, dehydration, nausea, vomit, abd pain, confusion/coma, smell ketones on breath

diagnosis ketoacidosis

high ketonemia or ketonuria, high glucose, low bicarb or ph

management ketoacidosis

replacement fluids (nacl or hartmann), replacement electrolytes (nacl w/ kcl), insulin (iv)

complications dka

cerebral edema, hypothermia

_______ is the characteristic metabolic er of uncontrolled t2dm

hyperosmolar hyperglycemic state

clinical features hyperosmolar hyperglycemic state

dehydration, stupor, coma

underlying illness evidence + risk cardiovasc events

management hyperosmolar hyperglycemic state

fluid replacement (nacl), prophylactic heparin

_______ is treated by rehydration and infusion bicarb

lactic acidosis

patho of microvasc complications

hyperglycemia → thickening cap + arteriole bm → ischemia + tissue dysfxn

consequences of hyperglycemia

formation advanced glycation end products (AGE), increased flux glucose thru sorbitol-polyol pathway, abnormal microvasc flow, increased GFs and cytokines, growth hormone hypersecretion

diabetic retinopathy - evolution

1. early, w/o vision loss : non-proliferative - damage to wall of small vessels → microaneurysms in retina → cotton wool spots = screening only

2. sight-threatening : pre-proliferative, v. loops, hemorrhages = need opthalmologist

3. proliferative : neovasc, hemorrhages = urgent referral

4. advanced - retinal fibrosis, retinal detach = urgent referral

maculopathy

hard exudates + microaneurysms or retinal hemorrhages

imaging thru ocular coherence tomography

management retinopathy

prevention

• intravitreal injection

• laser photocoagulation - treats new vessels of proliferative

• vitreoretinal surgery - if recurrent bleeding

other ways in which dm can affect eye

cataracts (must extract), refractory defects, external ocular palsies, glaucoma, blindness

diabetic nephropathy patho

• imicroalbuminuria and bp, renal hypertrophy → raised gfr

• glomerulosclerosis, thickening of bm

• decreasing gfr → eskd

_______ is associated w/ normochromic/cytic anemia and raised ers and crp, htn

diabetic nephropathy