Diabetes Flashcards by Jasmine Aikman

MODY definition

Maturity onset diabetes of the young
monogenic defect in glucose sensing in the pancreas+/ loss of insulin secretion that causes familial form of early onset (<25yo) diabetes

How well did you know this?

Not at all

Perfectly

MODY2 is caused by a gene defect for ____ which causes a ___ defect and the insulin threshold for a set blood glucose level ___

glucokinase
glucose sensing
increases

How well did you know this?

Not at all

Perfectly

MODY1+3 are caused by gene defects in ___ they ____+___

HNF (hepatocyte nuclear factors)4alpha and 1 alpha respectively
regulate beta cell differentiation and function

How well did you know this?

Not at all

Perfectly

MODY 4 is caused by a gene defect in ___

insulin promotor factor 1 (IPF1)

How well did you know this?

Not at all

Perfectly

MODY 5 is caused by a gene defect in ___

HNF-1beta

How well did you know this?

Not at all

Perfectly

MODY6 is caused by a gene defect in ___

NeuroD1/beta2 - neurogenic differentiation factor

How well did you know this?

Not at all

Perfectly

there are __ different genes that can be affected to cause MODY

How well did you know this?

Not at all

Perfectly

treatment for MODY is usually ___ because ___

sulfonylureas

beta cells still have some function

How well did you know this?

Not at all

Perfectly

the pathogenesis of T2D is

initial hyperglycaemia with hyperinsulinism

the primary problem is decreased tissue insulin sensitivity

How well did you know this?

Not at all

Perfectly

Main problem in T1D

AI loss of insulin secreting beta cells

How well did you know this?

Not at all

Perfectly

2 processes that insulin switches off

lipolysis

livergluconeogenesis

How well did you know this?

Not at all

Perfectly

5 processes insulin switches on

AA uptake in muscles
glycogen synth
DNA+protein synth
muscle and adipose glucose uptake and lipogenesis

How well did you know this?

Not at all

Perfectly

definition of phosphorylation

+phosphate group (PO4-) to any hydroxyl group by kinases - causes large -ve charge in molecule

How well did you know this?

Not at all

Perfectly

tyrosine kinase receptor for insulin is ___ = 2 ___ alpha subunits which ___
and 2 beta ___ subunits which
both linked by ___

dimeric
extracellular
bind to insulin
transmembrane
ATP binding and tyrosine kinase domain
disulfide bonds

How well did you know this?

Not at all

Perfectly

2 functions of phosphorylated IRS-1 after tyrosine kinase receptor for insulin is activated

activate Ras/MAPK pathway and gene expression

activate P13K, PKB (stims GLUT4 translocation to membrane and increases glucose uptake) and glycogen synth

How well did you know this?

Not at all

Perfectly

Leprechaunism/Donohue syndrome :
mode of inheritance
mutations in which gene
features

auto dom (rare)
gene for insulin receptor
elfin face, growth retarded, abscence of S/C fat and decreased muscle mass
severe insulin resistance

How well did you know this?

Not at all

Perfectly

Rabson Mendenhall syndrome:
mode of inheritance
mutations in which gene
features

auto recessive (rare)
insulin receptor
severe insulin resistance, dev. abnormalities, acanthosis nigricans, fasting hypoglycaemia, DKA

How well did you know this?

Not at all

Perfectly

Ketone bodies for in ____ from ___ after ___

liver mitochondrion
acetyl-CoA
beta-oxidation

How well did you know this?

Not at all

Perfectly

ketone bodies are important for energy for __+__

where they are converted to ___ for use in the ___

cardiac myocytes and renal cortex

acetyl CoA to enter the TCA

How well did you know this?

Not at all

Perfectly

the entrance of acetyl CoA into the TCA is dependent on ___ for formation of ___

oxaloacetate

citrate

How well did you know this?

Not at all

Perfectly

In starvation/diabetes ___ are oxidised for energy to ___ however ___ has been used for gluconeogenesis and so __ are formed

FAs
acetyl Co-A
oxaloacetate
ketone bodies

How well did you know this?

Not at all

Perfectly

In T2D they dont usually suffer from DKA because

high insulin concn inhibits hormone sensitive lipase so there is no excessive breakdown of fat resources

How well did you know this?

Not at all

Perfectly

Diabetes Insipidus is caused by a lack of __

ADH/vasopressin

How well did you know this?

Not at all

Perfectly

diagnostic criteria for diabetes based on HbA1c

<=41mmol/mol = normal
42-47 = pre-diabetes
>=48 = diabetes

How well did you know this?

Not at all

Perfectly

diagnostic criteria for diabetes based on fasting glucose

``` <=6mmol/l = normal 6.1-6.9 = prediabetes >7 = diabetes ```

diagnostic criteria for diabetes based on 2hr glucose in OGTT

``` <=7.7mmol/l = normal 7.8-11 = pre-diabetes >=11.1 = diabetes ```

diagnostic criteria for diabetes based on random glucose

>11.1mmol/l = diabetes

lipoatrophic diabetes =

genetic insulin action disorder

2 other endocrinopathies that can cause diabetes

acromegaly | Cushing's

drug induced diabetes (2)

steroids | thiazides

3 congenital conditions that can cause diabetes

Downs Turners Prader Willi

antibodies present in T1D | produce __ with ___ in the pancreas (histology)

anti-GAD anti-islet cell Igs insulinitis with lymphocyte infiltrate

T1D and T2D probability of microvasc complications at diagnosis

``` T1D = no signs usually T2D = 20% have them ```

T1D/T2D onset of symptoms at diagnosis is severe/insidious

``` T1D = severe T2D = insidious ```

discriminatory tests (3) for T1+2D

GAD/anti-islet cell Igs ketones C-peptides in the plasma

LADA = late onset ___ | often misdiagnosed as __ but will have __+__

T1D | T2D but will have ketones and GAD Ig

MODY is GAD IG __ and C peptide __

GAD -ve | C +ve

HbA1c = | measures

glycated Hb | glucose control over past 2-3 months

3 microvascular complications of diabetes

neuropathy nephropathy retinopathy

cause of 75% of diabetic mortality

cardiac and renal causes

in T2D histology =

amyloid in pancreas

2 HLA genotypes that most increase risk of T1D

DR3-DQ2 | DR4-DQ8

autoantibodies in T1D (4) | They are all though to differentiate from __

GAD 65 Ig (against glutamic acid decarboxylase IA-2 Ig (Islet antigen 2) ZnT8 Ig (ZnT8 transporter IAA (insulin) ICA - islet cell cytoplasmic Ig

ideal HbA1c for a T1D

48-58mmol/mol

if only have 50% of beta cell mass =>

hypergylcaemia

if only have __% of beta cell mass then need insulin

10%

blood glucose at presentation of T1/2D =

``` 1 = >25 2 = 10-25 ```

increased pancreatic auto-Igs in patients with recently diagnosed diabetes who dont initially require insulin =

LADA

___% of CF patients have diabetes at 20yo

25%

screen for diabetes in CF with ___ from age ___

OGTT from age 10

DIDMOAD/Wolfram syndrome features: | mode of inheritance =

Diabetes insipidus and mellitus, optic atropy, deaf, neuro abnormality mitochondrial

Bardet-Biedl syndrome features: | more likely if ___ parents

v obese, polydactyly, hypogonadal, visual and hearing impairment, mental retardation, diabetes consanguinous

Type 2 polyglandular endocrinopathy = T1D associated with any/all of: (5)

``` coeliacs addisons vitiligo primary hypogonadism primary hypothyroidism ```

Type 1 polyglandular endocrinopathy = T1D associated with any of: (9)

``` mild immune deficiency, primary hypoPT, pernicious anaemia, alopecia coeliacs addisons vitiligo primary hypogonadism primary hypothyroidism ```

tense tiredness is used to describe

hypoglycaemic symptoms

3 aims of insulin therapy

avoid hyperglycaemia +DKA reduce chronic complications acoid hypoglycaemia

rapid acting insulin analogues duration of action

5hrs

short acting - soluble/regular insulins duration of action

8hrs

intermediate acting insulins - isophane duration of action

20hrs

long acting insulin analogues duration of action

24hrs

basal bolus regime = ___ prandially and ___ before bed

rapid acting | long acting

analogues increase or decrease the risk of hypos?

decrease

bg target for a diabetic pre meal = | 1-2hrs after start of meal =

4-7mmol/l | <10

analogue prandial insulin examples (3)

novorapid (insulin aspart) lispro (humalog) glulisine (apidra)

soluble prandial insulins examples (2)

actrapid | humulin S

isophane basal insulin egs (2)

insulatard | humulin I

basal analogue insulin egs (2)

lantus (glargine) | levemir (determir)

DAFNE =

dose adjustment for normal eating | in diabetics on insulin

1 unit insulin : ___ carbs

10g

if postprandial bg is __ mmol/l > pre meal = increase insulin dose

use of insulin in a hypo?

DON'T OMIT it | treat hypo then give insulin as normal

if on IV insulin then bg aim is __mmol/l

5-12

if on IV insulin and bg >12mmol/l = check __

ketones

indications for a pancreas transplant =

severe hypos / metabolic complications incapacitating emotional/ clinical problems uncontrolled diabetes despite max Rx

In insulin resistance: insulin is inhibited via ___ responsible for phosphorylation of ____ => decreased __ + ___

serine kinases IRS-1 glucose transport and glycogen synthesis

__+___toxicity => beta cell dysfunction in T2D

gluco and lipotoxicity

if a T2D loses 1kg after diagnosis what is the increase in their length of survival

3-4months

T2D loses 10% of wt causes a decrease of __ in mortality

30-40%

BMI >22 increases diabetes risk by :

BMI 25 increases diabetes and CHD risk by

x8 T2D | x2 CHD

average BMI of presenting T2Ds

BMI 30 increased T2D risk by

40x

peripheral neuropathy: example = description

pain/loss of feeling in hands and feet | "glove and stocking" distal symmetrical/sensorimotor neuropathy

autonomic neuropathy could affect these 5 areas

``` hr +bp sweating bowel bladder sexual response ```

amyotrophy (weakness in legs) is caused by a ___ neuropathy

proximal

focal neuropathy results in : | 3 eg.s

a sudden weakness in a nerve/group of nerves | eg. palsies, foot drop and carpal tunnel

charcot foot, painless trauma and foot ulcers can be a result of a ___ neuropathy

peripheral

symptoms of a peripheral neuropathy

numbness/insensitivity tingle/burn cramps sensitivity to touch

Rx for pain in peripheral neuropathy =

``` amitriptyline duloxetine pregabalin gabapentin if localised = capsaicin ```

resting tachycardia and postural hypotension are common in ___ neuropathy

autonomic

treatment for gastroparesis

glycaemic control smaller portions and decrease fat and fibre metoclopramide (pro-motility) prochlorperazine, ondansetron (anti-emetic) painkillers

treatment for hyperhidrosis in autonomic neuropathy

topical glycopyrrolate clonidine botulinum

proximal neuropathy usually starts ___ | more common in ___ T2Ds

on one side of the body | elderly

diabetic nephropathy is characterised by

nephrotic syndrome and diffuse scarring of glomeruli => nodular glomerulosclerosis (aka Kimmelsteil-Wilson syndrome)

screening test for diabetic nephropathy

ACR (urinary albumin:creatinine ratio)

all diabetics are screened for nephropathy from age

dipstick testing urine in diabetics detects ___albuminaemia

macro NOT micro

bp target for all diabetics =

130/80

if a diabetic has microalbumin/proteinurea start them on a

ACEI/ARB

if eGFR is between 30-45 then what do you do to the dose of metformin?

half it

if eGFR <30 then what do you do to the dose of metformin

stop it

stop gliclazide if the eGFR is

<30

empagloflozin is stopped if the eGFR ___

decreases at all from normal

diabetic drug that is fine in CKD

piolitazone

stop exanatide/liraglutide if eGFR

<30

____ in diabetics causes reversible acute visual blurring

acute hyperglycaemia

mild retinopathy on fundoscopy -

only dot and blot haemorrhages and microaneurysms

cotton wool spots are indicative of a ___ area

ischaemic

hard exudates on fundoscopy are __

lipid break down products

5 signs that can be seen on fundoscopy of diabetic retinopathy

``` dot/blot/flame haemorrhages cotton wool spots hard exudate venous beading IRMA (intra retinal microvascular abnormalities) ```

severe complications of diabetic retinopathy (3)

retinal detachment massive haemorrhage 2ndry glaucoma

treatments for erectile dysfunction

antihypertensives (beta blocker, thiazides) | anti-depressants, tricyclics, SSRIs, analgesia

glucokinase mutated MODY causes ___ hyperglycaemia = ___ onset at __ Rx =

stable hyperglycaemia usually asymptomatic birth diet

Transcription factor (HNFs) mutated MODYs cause ___ hyperglycaemia onset at ___ Rx =

progressive hyperglycaemia adolescence 1/3diet, 1/3OHA, 1/3 insulin sulfonylureas extremely effective at reduced dose

neonatal diabetics require insulin at ___ old

3months

TNDM (transient neonatal) usually diagnosed at ___ and resolves around __

<1wk | 12wk

PNDM (permanent neonatal) usually diagnosed at ___ require __/___ mutation of __

0-6 wks insulin lifelong/sulfonylurea KIR6.2 channel

diabetic emergency caused by insulin deficiency and in increase in counter-regulatory hormones

DKA

3 things needed for a biochemical diagnosis of DKA

ketonaemia >3mmol/l or ketonuria >2 bg >11 or known diabetes bicarbonate <15mmol/l/ venous pH <7.3

common precipitants of DKA

infection illicit drugs/alcohol non-compliance newly diagnosed diabetes

in DKA creatinine __ and sodium __ and amylase __

creatinine increased sodium decreased amylase raised

the ketone measured if it is from blood

beta-hydroxybutyrate

the ketone measured if it is from urine

acetoacetate

the cause of mortality in DKA for adults (3) and kids (1)

hypokalaemia, aspiration pneumonia, ARDS | cerebral oedema

replacement treatment in DKA

fluids (0.9NaCl), insulin, K+ | and prophylactic LMWH

normal blood ketone level

<0.6 mmol/l

HHS more likely in T1/2D? due to ___

2 | high-refined carb intake

mortality is greater in DKA/HHS?

HHS (=10-50%)

treatment for HHS

``` fluids (cautiously as overload risk) insulin (slower than in DKA) Na+ LMWH screen for sepsis and vascular event ```

``` biochemistry HHS - glucose = renal = Na+= osmolarity= pH= ```

``` around 60mmol/l >DKA creatinine up and eGFR down around 400 (norm - 285-295) less acidotic that DKA ```

equation for osmolarity =

2x [Na+K]+urea +glucose

ion gap in lactic acidosis is ___

raised

ion gap equation

[Na+K]-[Cl + HCO3]

the type of lactic acidosis that is associated with tissue hypoxaemia

type A

Type B lactic acidosis is associated with

liver disease, leukaemic states, diabetes, metformin in renal failure

biochemistry of lactic acidosis

``` HCO3 low raised anion gap glucose often raised no ketonuria increased phosphate ```

treatment for alcohol induced ketoacidosis

``` pabrinex (high dose vitamins) IV fluids (esp dextrose) may need insulin ```

for hypoglycaemia treatment if the patient is awake =

15-20g rapidly acting carb eg. 90-120ml lucozade then 15-20g of slow acting eg. a sandwich

avoid exercise if __ or ___

ketones present | bg >14

nutritive sweetener that needs insulin adjusted for it

xylotol

non-nutritive sweetener that has no effect on bg

aspartame

tense tiredness describes the symptoms of

hypoglycaemia

hypo responses are impaired during sleep because

adrenaline, cortisol and glucagon levels dip

``` GP clinical targets (QoF) for diabetics BMI HbA1c bp total chol, LDL and tris ```

BMI <25 HbA1c 75 mmol/mol bp = <=140/80 <5, <3, <2.3

if BMI is >25 Rx for diabetes =

metformin

if bmi < 25 Rx for diabetes =

gliclazide up to 160mg bd

____ increase the effects of repaglinide in diabetes

CYTP450 inhibitors - ketoconazole + nacroglides | NSAIDS

____ decrease the effects of repaglinide in diabetes

CYTP450 inducers - rifampicin, phenobarbitone, carbamazepine

repaglinide is _+_ acting and depends on ___, dose = ___ taken before each meal

fast and short bg levels 0.5-4mg

bg monitoring is recommended for diabetics who :

are on insulin | on a sulfonylurea

DKA guidelines for <18yos key differences from adult protocol (4)

based on weight careful fluid resus highlighted risk of cerebral oedema insulin started 1 hr after IV fluids started

bg targets for inpatient diabetics

6-12 mmol/l

if diabetic can swallow but are drowsy/confused Rx for hypo =

1.5-2 tubes of glucose gel into buccal mucose

dont use ___ in PO hypo agent induced hypo

glucagon

rapid acting insulins =

humalog. novorapid | apidra

short/soluble insulins = | when to take

actrapid humulin S insuman rapid - take 30 min before eating

number in a fixed mix insulin tells you

the percentage of short acting

rapid intermediate insulin mixes

Humalog mix 25, 50 | novomix 30

short intermediate insulin mix

humulin M3 | insuman combi 15, 25, 50

isophane/intermediate insulins

insulatard humulin I insuman basal

long analogue insulins

lantus | levemir

adjust insulin doses by ___ each time

10%

always prescribe __ with IV insulin

IV fluids

continue to give ___ if on IV insulin but usually on MDII

SC basal insulin

gestational diabetes develops in the __ trimester

2nd

tolbutamide, chlorpropamide are

sulfonylureas

avoid metformin in these cases

``` renal failure alcoholic cirrhosis chronic lung disease HF ```

piaglitazone is a

TZD

hyperglycaemic response to slight hypo =

somogyi effect

poyol/aldose reductase pathway is normally inactive but activates if

increased intracellular glucose

poyol/aldose reductase pathway: | _____ has a higher Km for glucose than glucokinase so only active if ___

aldose reductase | glucose in much excess

poyol/aldose reductase pathway: | aldose reductase catalyses __>___

glucose to sorbitol

poyol/aldose reductase pathway: | the excess glucose that is more than can be converted to sorbitol is converted to __+__

methylglyoxal and acetol (glycating sugars)

poyol/aldose reductase pathway: ___ exerts osmotic P causing cell damage it is converted to __ by _ and diffuses out of the cell

sorbitol fructose sorbitol dehydrogenase

poyol/aldose reductase pathway causes the production of ___ as __+__+ __bind to proteins which are then less functional than normal. Levels measured by ___

AGE (advanced glycation end-products) methylgloxal and acetol (glycating sugars) + excess glucose HbA1c

pathway involved in production of AGEs in diabetes

poyol/aldose reductase pathway

monofilament used to check diabetic foot P sensation

10g

3 neuropathies diabetics can get

``` hyperglycaemic (discomfort lower legs - resolves when bg does) acute painful diabetic (due to rapid wt loss and poor bg control - severe burning pain - takes 12-24m to resolve) distal symmetrical (most common) ```

tropicamide =

mydriatic eye drops

neuropathic ulcers in diabetics are found on __/__

MT heads or big toe usually

ischaemic foot ulcers site =

margins of feet

bag of bones foot

charcot foot

if BMI >30 this diabetic drug would be grand

S/C GLP-1 agonists