Diabetes and Impaired glucose tolerance Flashcards
When is a diagnosis of diabetes made?
Fasting glucose >7mmol/L
Two hour plasma glucose OR Random plasma glucose >11.1 mmol/L
HbA1c >48 mmol/mol
What two criteria have to both be met for diagnosis of impaired glucose tolerance?
Fasting plasma glucose < 7 mmol/L
AND
>7.8 but <11.1 two hour plasma glucose
Impaired fasting glucose when can diagnose
If first or both of following criteria are met
Fasting plasma glucose between 6.1-6.9
AND (if measured
<7.8 two hour plasma glucose
What HbA2c is prediabetes / IFG or IGT
42-47
Fasting glucose 6.1-6.9
What is the target for HbA1c if diabetes is being managed with any drug that may cause hypoglycaemia eg sulfonylurea?
53 mmol/mol
Autoantiboides in T1DM
Glutamic acid decarboxylase (GAD 65)
Islet cells (not specific or sensitive)
insulin
Tyrosine phosphatase (IA2 +IA2B)
Zinc transporter (ZnT8)
>80% + for GAD, IA2 or AnT8 n
% of T1DM with HLA
90% DR3 or DR4
Type 1 vs type 2 diabetes genes
type 1 - HLA
tyoe 2 - TCF7L2
May deevlop insulin resitance but may not
What is the most powerful genes in terms of causing T2DM
tcf7l2
polygenic (50 genes w small effects)
Secondary diabetes mellitus
Pancreatic disease and pancreatitis
Cystic fibrosis
Haemochromatosis (iron deposition)
Drug induced
Types of diabetes
1 and 2
Secondary
Monogenic
Congenital and neonatal
Syndromic
Chromosomal - increased risk
Mitochondiral
Syndromic diabetes causes
Lipodystrophies, prader-willi syndrome, myotonic dystrophy, wolfram (DIDMOAD)
Features of mitochondrial disease causing T1DM
Deafness and cardio-neural problems
What drugs can cause diabetes
Chronic steroid use
Calcineurin inhibitors
Statins
Major antipsychotic agents
HAART
Ass endocrinopathies with diabetes and the hormone in excess that causes that in each
Cushings including iatrogenic - glucocorticoids
Acromegaly - growth hormones
Phaeochromocytoma - catecholamines
Glucagonomas
Somatostatinomas
Hyperthyroidism - autoimmune link w type 1
What drugs to offer when patient symptomatically hyperglycaemic
Insulin or sulonylurea
What do you use if metformin standard release is not tolerated?
Metformin modified release
Alternatives to metformin
DPP4 inhbitor
Pioglitzone
Sulgoylurea
SGLT2 inhibitor
When to consider insulin based treatemnet
After triple therapy with metformin
After dual therapy if metformin not tolerated
Combinations:
Metformin + DPP4i + sulfonylurea
M +pioglitazone + sulfonylurea
M +pioglitazone/sulfonylurea + SGLT2i
When consider metformin + sulfonylurea + GLP-1 agonist if
Triple therapy ineffective, contraindicated OR
BMI >35 in europeans who have comorbidites ass
BMI < 35 w significant occupational implications or weight loss would beneift other comorbidities
Treatment lines of HbA1c
<48
<58 - increase medication from dual to triple therapy
What to do if o triple therapy weight decline >3% and HbA1c >3% in 6 months
Continue with only GLP-1 analogue
What does insulin based treatment consist of
Continue metfrmin if tolerated
Offer NPH insulin once or twice daily, consider offering short actin insulin also or biphasic esp if HbA1c >75
When consider offering biphasic preps containing short acting insulin
Prefers injecting immerdiately before a meal
Hypoglycaemic
Blood glucose levels markedly raised after meals
Cause of diabetes
Decreased beta cell function and insulin function in muscle and liver
What is importnat to also consider in diabetes
Lipid levels and Qrisk score, other cardiac risk factors and how to control them
Weight loss, education about remission
Mechanism of action of metformin
Reduced hepatic glucose output
Increased insulin sensitivity
What diabetic medication can help weight loss?
Metformin
GLP-1 analogues nad DPP4-inhibitors
SGLT2 inhibitors
Side effects of metformin
GI upset - try modified release and start on low dose, titrate up
RARE - lactic acidosis
MOA of DPP4 inhibitors
sTOP glp-1 BREAKDOwn, increase GLP-1 to act on beta cells in pancreas to increase insulin release
Incretin based
Examples of SGLT2 inhibitors
Dapagliflozin, canagliflozin, empagliflozin
MOA of SGLT2 inhibitors
Block reabsorption of glucose at proximal tubule - increase excretion in urine
Side effect of SGLT2 inhibitors
UTI due to increase glucose in urine
What extra benefits do SGLT2 inhibtiors have
Cardiovascular risk reduction, reduced HF hosptialisation
MOA of sulfonylureas
Stimulates insulin secretion from beta cells
V fast onset - fast reduction of glucose
Negative of sulonylureas
Weight gain
cause hypos because of speed
Piaglitazone MOA
Improves tissue sensitivity to insulin
Porblems with piaglitazone
Fluid retnetion
Weight gain
HF - increased straing on the heart esp if preexisitng conditions
GLP 1 advantages
Weight reduction, CVS risk reduction (Semaglutide, dulaglutide, liraglutide)
Less hypoglycaemia when used on own than dual therapy but as effective - occupational beenfits eg drivers
Semaglutide can be taken orally
GI side effects
What diabetic drugs reduce cardiac risk
SGLT2 inhibtors and GLP-1 analogues
Daily vs weekly GLP-1 analogues
Liraglutide (once), exenatide (twice) = daily
Exenatice LAR, dulaglutide, semalgutide - once a week injection
Advantages of insulin
Direct effect on blood glucose
Improves glycaemic control
Drawbacks of insulin
Hypo riskk
Weight gain
Occupational concerns
INjection
Intermediate acting insulins
NPH insulin - insulatard, humilin I
Long acting insulins
Glargine, degludec
Short acting insulins
Actrapid, insulin aspart, inulin lispro
Mixed insulins
Novomix 30 (30% short acting)
Humulag mix 25 (25% SA)
