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EndocrineJaz > Diabetes > Flashcards

Diabetes Flashcards

1
Q

MODY definition

A

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

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2
Q

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

A

glucokinase
glucose sensing
increases

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3
Q

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

A

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

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4
Q

MODY 4 is caused by a gene defect in ___

A

insulin promotor factor 1 (IPF1)

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5
Q

MODY 5 is caused by a gene defect in ___

A

HNF-1beta

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6
Q

MODY6 is caused by a gene defect in ___

A

NeuroD1/beta2 - neurogenic differentiation factor

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7
Q

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

A

6

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8
Q

treatment for MODY is usually ___ because ___

A

sulfonylureas

beta cells still have some function

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9
Q

the pathogenesis of T2D is

A

initial hyperglycaemia with hyperinsulinism

the primary problem is decreased tissue insulin sensitivity

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10
Q

Main problem in T1D

A

AI loss of insulin secreting beta cells

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11
Q

2 processes that insulin switches off

A

lipolysis

livergluconeogenesis

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12
Q

5 processes insulin switches on

A

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

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13
Q

definition of phosphorylation

A

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

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14
Q

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

A 
dimeric
extracellular
bind to insulin
transmembrane
ATP binding and tyrosine kinase domain
disulfide bonds
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15
Q

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

A

activate Ras/MAPK pathway and gene expression

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

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16
Q

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

A

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

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17
Q

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

A

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

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18
Q

Ketone bodies for in ____ from ___ after ___

A

liver mitochondrion
acetyl-CoA
beta-oxidation

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19
Q

ketone bodies are important for energy for __+__

where they are converted to ___ for use in the ___

A

cardiac myocytes and renal cortex

acetyl CoA to enter the TCA

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20
Q

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

A

oxaloacetate

citrate

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21
Q

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

A

FAs
acetyl Co-A
oxaloacetate
ketone bodies

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22
Q

In T2D they dont usually suffer from DKA because

A

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

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23
Q

Diabetes Insipidus is caused by a lack of __

A

ADH/vasopressin

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24
Q

diagnostic criteria for diabetes based on HbA1c

A 
<=41mmol/mol = normal
42-47 = pre-diabetes
>=48 = diabetes
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25
Q

diagnostic criteria for diabetes based on fasting glucose

A 
<=6mmol/l = normal
6.1-6.9 = prediabetes
>7 = diabetes
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26
Q

diagnostic criteria for diabetes based on 2hr glucose in OGTT

A 
<=7.7mmol/l = normal
7.8-11 = pre-diabetes
>=11.1 = diabetes
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27
Q

diagnostic criteria for diabetes based on random glucose

A

> 11.1mmol/l = diabetes

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28
Q

lipoatrophic diabetes =

A

genetic insulin action disorder

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29
Q

2 other endocrinopathies that can cause diabetes

A

acromegaly

Cushing’s

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30
Q

drug induced diabetes (2)

A

steroids

thiazides

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31
Q

3 congenital conditions that can cause diabetes

A

Downs
Turners
Prader Willi

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32
Q

antibodies present in T1D

produce __ with ___ in the pancreas (histology)

A

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

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33
Q

T1D and T2D probability of microvasc complications at diagnosis

A 
T1D = no signs usually
T2D = 20% have them
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34
Q

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

A 
T1D = severe
T2D = insidious
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35
Q

discriminatory tests (3) for T1+2D

A

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

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36
Q

LADA = late onset ___

often misdiagnosed as __ but will have __+__

A

T1D

T2D but will have ketones and GAD Ig

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37
Q

MODY is GAD IG __ and C peptide __

A

GAD -ve

C +ve

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38
Q

HbA1c =

measures

A

glycated Hb

glucose control over past 2-3 months

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39
Q

3 microvascular complications of diabetes

A

neuropathy
nephropathy
retinopathy

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40
Q

cause of 75% of diabetic mortality

A

cardiac and renal causes

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41
Q

in T2D histology =

A

amyloid in pancreas

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42
Q

2 HLA genotypes that most increase risk of T1D

A

DR3-DQ2

DR4-DQ8

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43
Q

autoantibodies in T1D (4)

They are all though to differentiate from __

A

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

ICA - islet cell cytoplasmic Ig

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44
Q

ideal HbA1c for a T1D

A

48-58mmol/mol

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45
Q

if only have 50% of beta cell mass =>

A

hypergylcaemia

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46
Q

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

A

10%

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47
Q

blood glucose at presentation of T1/2D =

A 
1 = >25
2 = 10-25
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48
Q

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

A

LADA

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49
Q

___% of CF patients have diabetes at 20yo

A

25%

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50
Q

screen for diabetes in CF with ___ from age ___

A

OGTT from age 10

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51
Q

DIDMOAD/Wolfram syndrome features:

mode of inheritance =

A

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

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52
Q

Bardet-Biedl syndrome features:

more likely if ___ parents

A

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

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53
Q

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

A 
coeliacs
addisons
vitiligo
primary hypogonadism
primary hypothyroidism
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54
Q

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

A 
mild immune deficiency, primary hypoPT, pernicious anaemia, alopecia
coeliacs
addisons
vitiligo
primary hypogonadism
primary hypothyroidism
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55
Q

tense tiredness is used to describe

A

hypoglycaemic symptoms

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56
Q

3 aims of insulin therapy

A

avoid hyperglycaemia +DKA
reduce chronic complications
acoid hypoglycaemia

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57
Q

rapid acting insulin analogues duration of action

A

5hrs

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58
Q

short acting - soluble/regular insulins duration of action

A

8hrs

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59
Q

intermediate acting insulins - isophane duration of action

A

20hrs

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60
Q

long acting insulin analogues duration of action

A

24hrs

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61
Q

basal bolus regime = ___ prandially and ___ before bed

A

rapid acting

long acting

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62
Q

analogues increase or decrease the risk of hypos?

A

decrease

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63
Q

bg target for a diabetic pre meal =

1-2hrs after start of meal =

A

4-7mmol/l

<10

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64
Q

analogue prandial insulin examples (3)

A

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

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65
Q

soluble prandial insulins examples (2)

A

actrapid

humulin S

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66
Q

isophane basal insulin egs (2)

A

insulatard

humulin I

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67
Q

basal analogue insulin egs (2)

A

lantus (glargine)

levemir (determir)

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68
Q

DAFNE =

A

dose adjustment for normal eating

in diabetics on insulin

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69
Q

1 unit insulin : ___ carbs

A

10g

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70
Q

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

A

2

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71
Q

use of insulin in a hypo?

A

DON’T OMIT it

treat hypo then give insulin as normal

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72
Q

if on IV insulin then bg aim is __mmol/l

A

5-12

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73
Q

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

A

ketones

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74
Q

indications for a pancreas transplant =

A

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

75
Q

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

A

serine kinases
IRS-1
glucose transport and glycogen synthesis

76
Q

__+___toxicity => beta cell dysfunction in T2D

A

gluco and lipotoxicity

77
Q

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

78
Q

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

79
Q

BMI >22 increases diabetes risk by :

80
Q

BMI 25 increases diabetes and CHD risk by

A

x8 T2D

x2 CHD

81
Q

average BMI of presenting T2Ds

82
Q

BMI 30 increased T2D risk by

83
Q

peripheral neuropathy:
example =
description

A

pain/loss of feeling in hands and feet

“glove and stocking” distal symmetrical/sensorimotor neuropathy

84
Q

autonomic neuropathy could affect these 5 areas

A 
hr +bp
sweating
bowel
bladder
sexual response
85
Q

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

86
Q

focal neuropathy results in :

3 eg.s

A

a sudden weakness in a nerve/group of nerves

eg. palsies, foot drop and carpal tunnel

87
Q

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

A

peripheral

88
Q

symptoms of a peripheral neuropathy

A

numbness/insensitivity
tingle/burn
cramps
sensitivity to touch

89
Q

Rx for pain in peripheral neuropathy =

A 
amitriptyline
duloxetine
pregabalin
gabapentin
if localised = capsaicin
90
Q

resting tachycardia and postural hypotension are common in ___ neuropathy

91
Q

treatment for gastroparesis

A

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

92
Q

treatment for hyperhidrosis in autonomic neuropathy

A

topical glycopyrrolate
clonidine
botulinum

93
Q

proximal neuropathy usually starts ___

more common in ___ T2Ds

A

on one side of the body

elderly

94
Q

diabetic nephropathy is characterised by

A

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

95
Q

screening test for diabetic nephropathy

A

ACR (urinary albumin:creatinine ratio)

96
Q

all diabetics are screened for nephropathy from age

97
Q

dipstick testing urine in diabetics detects ___albuminaemia

A

macro NOT micro

98
Q

bp target for all diabetics =

99
Q

if a diabetic has microalbumin/proteinurea start them on a

100
Q

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

101
Q

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

102
Q

stop gliclazide if the eGFR is

103
Q

empagloflozin is stopped if the eGFR ___

A

decreases at all from normal

104
Q

diabetic drug that is fine in CKD

A

piolitazone

105
Q

stop exanatide/liraglutide if eGFR

106
Q

____ in diabetics causes reversible acute visual blurring

A

acute hyperglycaemia

107
Q

mild retinopathy on fundoscopy -

A

only dot and blot haemorrhages and microaneurysms

108
Q

cotton wool spots are indicative of a ___ area

109
Q

hard exudates on fundoscopy are __

A

lipid break down products

110
Q

5 signs that can be seen on fundoscopy of diabetic retinopathy

A 
dot/blot/flame haemorrhages
cotton wool spots
hard exudate
venous beading
IRMA (intra retinal microvascular abnormalities)
111
Q

severe complications of diabetic retinopathy (3)

A

retinal detachment
massive haemorrhage
2ndry glaucoma

112
Q

treatments for erectile dysfunction

A

antihypertensives (beta blocker, thiazides)

anti-depressants, tricyclics, SSRIs, analgesia

113
Q

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

A

stable hyperglycaemia
usually asymptomatic
birth
diet

114
Q

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

A

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

115
Q

neonatal diabetics require insulin at ___ old

116
Q

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

117
Q

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

A

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

118
Q

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

119
Q

3 things needed for a biochemical diagnosis of DKA

A

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

120
Q

common precipitants of DKA

A

infection
illicit drugs/alcohol
non-compliance
newly diagnosed diabetes

121
Q

in DKA creatinine __ and sodium __ and amylase __

A

creatinine increased
sodium decreased
amylase raised

122
Q

the ketone measured if it is from blood

A

beta-hydroxybutyrate

123
Q

the ketone measured if it is from urine

A

acetoacetate

124
Q

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

A

hypokalaemia, aspiration pneumonia, ARDS

cerebral oedema

125
Q

replacement treatment in DKA

A

fluids (0.9NaCl), insulin, K+

and prophylactic LMWH

126
Q

normal blood ketone level

A

<0.6 mmol/l

127
Q

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

A

2

high-refined carb intake

128
Q

mortality is greater in DKA/HHS?

A

HHS (=10-50%)

129
Q

treatment for HHS

A 
fluids (cautiously as overload risk)
insulin (slower than in DKA)
Na+
LMWH
screen for sepsis and vascular event
130
Q 
biochemistry HHS - glucose =
renal =
Na+=
osmolarity=
pH=
A 
around 60mmol/l >DKA
creatinine up and eGFR down
around 400 (norm - 285-295)
less acidotic that DKA
131
Q

equation for osmolarity =

A

2x [Na+K]+urea +glucose

132
Q

ion gap in lactic acidosis is ___

133
Q

ion gap equation

A

[Na+K]-[Cl + HCO3]

134
Q

the type of lactic acidosis that is associated with tissue hypoxaemia

135
Q

Type B lactic acidosis is associated with

A

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

136
Q

biochemistry of lactic acidosis

A 
HCO3 low
raised anion gap
glucose often raised
no ketonuria
increased phosphate
137
Q

treatment for alcohol induced ketoacidosis

A 
pabrinex (high dose vitamins)
IV fluids (esp dextrose)
may need insulin
138
Q

for hypoglycaemia treatment if the patient is awake =

A

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

139
Q

avoid exercise if __ or ___

A

ketones present

bg >14

140
Q

nutritive sweetener that needs insulin adjusted for it

141
Q

non-nutritive sweetener that has no effect on bg

142
Q

tense tiredness describes the symptoms of

A

hypoglycaemia

143
Q

hypo responses are impaired during sleep because

A

adrenaline, cortisol and glucagon levels dip

144
Q 
GP clinical targets (QoF) for diabetics
BMI
HbA1c
bp
total chol, LDL and tris
A

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

145
Q

if BMI is >25 Rx for diabetes =

146
Q

if bmi < 25 Rx for diabetes =

A

gliclazide up to 160mg bd

147
Q

____ increase the effects of repaglinide in diabetes

A

CYTP450 inhibitors - ketoconazole + nacroglides

NSAIDS

148
Q

____ decrease the effects of repaglinide in diabetes

A

CYTP450 inducers - rifampicin, phenobarbitone, carbamazepine

149
Q

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

A

fast and short
bg levels
0.5-4mg

150
Q

bg monitoring is recommended for diabetics who :

A

are on insulin

on a sulfonylurea

151
Q

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

A

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

152
Q

bg targets for inpatient diabetics

A

6-12 mmol/l

153
Q

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

A

1.5-2 tubes of glucose gel into buccal mucose

154
Q

dont use ___ in PO hypo agent induced hypo

155
Q

rapid acting insulins =

A

humalog. novorapid

apidra

156
Q

short/soluble insulins =

when to take

A

actrapid
humulin S
insuman rapid - take 30 min before eating

157
Q

number in a fixed mix insulin tells you

A

the percentage of short acting

158
Q

rapid intermediate insulin mixes

A

Humalog mix 25, 50

novomix 30

159
Q

short intermediate insulin mix

A

humulin M3

insuman combi 15, 25, 50

160
Q

isophane/intermediate insulins

A

insulatard
humulin I
insuman basal

161
Q

long analogue insulins

A

lantus

levemir

162
Q

adjust insulin doses by ___ each time

163
Q

always prescribe __ with IV insulin

164
Q

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

A

SC basal insulin

165
Q

gestational diabetes develops in the __ trimester

166
Q

tolbutamide, chlorpropamide are

A

sulfonylureas

167
Q

avoid metformin in these cases

A 
renal failure
alcoholic
cirrhosis
chronic lung disease
HF
168
Q

piaglitazone is a

169
Q

hyperglycaemic response to slight hypo =

A

somogyi effect

170
Q

poyol/aldose reductase pathway is normally inactive but activates if

A

increased intracellular glucose

171
Q

poyol/aldose reductase pathway:

_____ has a higher Km for glucose than glucokinase so only active if ___

A

aldose reductase

glucose in much excess

172
Q

poyol/aldose reductase pathway:

aldose reductase catalyses __>___

A

glucose to sorbitol

173
Q

poyol/aldose reductase pathway:

the excess glucose that is more than can be converted to sorbitol is converted to __+__

A

methylglyoxal and acetol (glycating sugars)

174
Q

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

A

sorbitol
fructose
sorbitol dehydrogenase

175
Q

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

A

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

176
Q

pathway involved in production of AGEs in diabetes

A

poyol/aldose reductase pathway

177
Q

monofilament used to check diabetic foot P sensation

178
Q

3 neuropathies diabetics can get

A 
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)
179
Q

tropicamide =

A

mydriatic eye drops

180
Q

neuropathic ulcers in diabetics are found on __/__

A

MT heads or big toe usually

181
Q

ischaemic foot ulcers site =

A

margins of feet

182
Q

bag of bones foot

A

charcot foot

183
Q

if BMI >30 this diabetic drug would be grand

A

S/C GLP-1 agonists

EndocrineJaz (15 decks)

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