Diabetes Flashcards
What is the definition of diabetes by WHO?
Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose (or blood sugar), which leads over time to serious damage to the heart, blood vessels, eyes, kidneys, and nerves.
What is the most common type of diabetes?
Type 2
Explain how type 1 diabetes is an auto immune disorder?
Develop antibodies that attack the beta cells which causes insulitis and eventually results in complete destruction and inability to produce insulin.
4 Ts for children with type 1 diabetes?
Tired
Toilet (increased frequency)
Thirsty
Thinner
Describe classic type 1 diabetes presentation?
Pre-school and peri-puberty Small peak in late 30’s Usually lean Acute Onset severe symptoms severe weight loss ketonuria and/or metabolic acidosis no evidence of microvascular disease at diagnosis immediate and permanent requirement for insulin
Describe classic type 2 diabetes presentation?
middle-aged/elderly
usually obese
pre-diagnosis duration of probably 6-10 years
insidious onset over weeks to years
ketonuria minimal or absent
evidence of micro-vascular disease at diagnosis in 20 %
managed initially with diet + tablets
Describe 4 blood tests for diabetes
Fasting glucose
HbA1c
2hr glucose in OGTT
Random Glucose
What is the 2hr glucose in OGTT?
Oral glucose tolerance test, you measure fasting glucose then give sugary solution and see what there glucose is after 2hrs.
Describe HbA1c test and how it works?
It measures glaciated haemoglobin so gives an idea of your blood glucose for the last 2-3months.
What is the diagnostic criteria for diabetes?
HbA1c: 48 mm/mol or above Fasting glucose: 7mm/mol or above 2hr glucose in OGTT: 11.1mm/mol or above Random glucose: 11.1mm/mol or above One abnormal value for symptomatic individuals and two are needed for asymptomatic people. Glucose tolerance test usually only required for borderline cases or gestational diabetes.
Fasting is defined as no calorific intake for at least…
8 hrs
Testing for diabetes or prediabetes in asymptomatic adults should be considered in…
First-degree relative with diabetes
High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander)
History of CVD
Hypertension (≥140/90 mmHg or on therapy for hypertension)
HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L)
Women with polycystic ovary syndrome
Physical inactivity
Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
What are normal blood results?
HbA1c: 41 mm/mol or below
Fasting glucose: 6mm/mol or below
2hr glucose in OGTT: 7.7mm/mol or below
Describe the 4 types of diabetes?
Type 1: auto immunity to beta cells no insulin
Type 2: increased resistance to insulin action
Type 3: Gestational diabetes (Any degree of glucose intolerance arising or diagnosed during pregnancy)
Type 4: Others causes e.g. pancreatic disease, endocrine disorders, drug induced, genetic related e.g. CF
Risk factors for type 2 diabetes?
Obesity
Genetic susceptibility
South East Asian have higher rates in slimmer adults
Family history
Associated with hypertension, hyperlipidaemia, hyperglycaemia and polycystic ovarian syndrome (so must check for these)
Describe presentation of type 2 diabetes?
May present asymptomatic from screening or be an incidental finding in hospital.
If symptoms: usually doesn’t present acutely, and often signs of microvascular complications already.
Symptoms: thirst, polyuria, thrush, weakness, fatigue, blurred vision, infections, complications e.g. neuropathy and retinopathy.
Type 2 diabetes is a diagnosis of _________
exclusion
Why does polyuria occur in diabetes?
Increased urination: Occurs due to excess sugar in the blood. Normally when kidneys create urine they reabsorb glucose but instead it goes into the urine as body attempts to lower glucose.
Why does polydipsia occur in diabetes?
Increased thirst: glucose in urine pulls water out with it
Why does thrush occur in diabetes?
High glucose is favourable conditions may also have irritated skin and a lower immune response
Why does fatigue occur in diabetes?
Blood sugar changing and also dehydration
Why does blurred vision occur in diabetes?
High blood sugar causes the lens in the eye to swell
Explain tests that can rule out other forms of diabetes and rule in type 2?
Test for type 1 antibodies in combination 95% sensitivity so if don’t have only 5% chance it’s type 1. GAD, IA-2 and ZnT8.
Measure C-peptide, this will only decrease after 3yrs (children), 5yrs (adults) in Type 1 so is useful for confirming type 1 as opposed to diagnosing type 2 (NOTE occasionally type 1 has persistent C-peptide)
Can measure C peptide in type 2s after fasting.
Describe overview of treatment for type 2?
Lifestyle changes in everyone then
Pharmacological agents and manage and screen for microvascular complications
Type 2 should treat to lower HbA1c to ______
Why?
53mmol/l
This reduces risks of complications but don’t try and get any lower as bad results from study
Explain the pharmacological treatment of type 2 diabetes?
Metformin- first line
Sulphonylureas- first line when metformin contraindicated or intolerant. Can also be add on treatment.
Thiazolidinediones, DPP4i, SGLT2i and GLP agonists also all add ons.
Insulin last resort.
SGLT2i given to those with established CV disease or sometimes GLP agonists
GLP given to those BMI over 30 with poor control as help lose weight.
When is metformin contraindicated?
Renal impairment
Contraindications for Thiazolidinediones? Adverse effects?
Many actually taken off market
Pioglitazone contraindicated in HF and increases risk of fractures as well as bladder cancer.
Describe BMI calculation and interpretation?
BMI= kg/m2
Normal= 18.5-24.9
Overweight= 25-29.9
Obese= 30 and above
Why can waist circumference give more information than BMI?
BMI doesn’t differentiate between fat or muscle whereas waist circumference measures visceral fat.
Describe normal and overweight waist circumferences?
- Male high WC= 94-102 and very high more than 102
* Women high WC= 80-88 and very high more than 88
What ethnicity risks from obesity start at lighter weights?
South asians
What are the physical activity guidelines?
150 mins of moderate activity a week or 75 mins of vigorous activity or combination
Plus strength 2 days a week
Minimise sedentary time
Older adults should do balance improving things
Define Monogenic Diabetes
Rare types of diabetes caused by a single gene mutation.
When should you consider monogenic diabetes?
In people presenting with early onset diabetes in association with an affected parent and early onset diabetes in approx. 50% of relatives.
MODY is autosomal ________
dominant
Explain two genetic defects that can cause MODY?
Glucokinase defect
Defects in HNF transcription factors particularly HNF-1alpha
Describe how glucokinase defect cause MODY and what the treatment is
The gene helps the body recognise how high the blood glucose levels are so without this blood glucose is slightly higher than normal.
Will have a higher than normal glucose from birth
Complications are rare and there is no evidence that treatment is beneficial, only relevant to know about in pregnancy.
Compare onset of glucokinase MODY vs HNF-1alpha MODY
Glucokinase will have hyperglycaemia from birth as just have different set homeostatic point whereas in HNF-1alpha the diabetes will develop gradually with onset in adolescence early 20s
Complications occur in glucokinase or HNF-1alpha MODY?
HNF-1alpha complications are much more common
Don’t get complications in glucokinase
Describe how HNF-1alpha mutation causes MODY and what the treatment is
Transcription factor mutation that results in less insulin being produced by the pancreas
Diabetes develops in adolescence/ early 20s complications are frequent
This should be treated with SUs (gliclazide) as this allows insulin to be secreted so is important to differentiate from Type 2
Treatment of HNF-1 alpha MODY vs glucokinase?
Glucokinase doesn’t need treatment
HNF-1alpha give sulfonylureas (gliclazide)
Define neonatal diabetes?
Diabetes that requires insulin treatment in the 1st 3 month
Unlikely to be type 1 diabetes if child is under…
1
Describe transient and permanent neonatal diabetes?
Transient neonatal diabetes is usually diagnosed within the first week and resolves by week 12. Can get permanent neonatal diabetes which is usually diagnosed 0-6 weeks and needs lifelong treatment.
What are many forms of neonatal diabetes due to?
Mutations in KATP channel in sensing ATP so can be treated with SUs which will close the channel if ATP cannot.
Treatment of neonatal diabetes?
If mutation in KATP channel in sensing ATP can give SUs (glibenclamide) as this will help close the channel so insulin can be secreted
Some may need insulin treatment.
In primary care what are high risk groups that should be recalled annually to screen for diabetes? What test is done?
Fasting Glucose plasma measurement
- Impaired glucose tolerance (pre-diabetes)
- Impaired fasting glycaemia (pre-diabetes)
- Past history of gestational diabetes
What is gestational diabetes?
Gestational diabetes is high blood sugar (glucose) that develops during pregnancy and usually disappears after giving birth. It happens when your body cannot produce enough insulin to meet your extra needs in pregnancy.
Describe when diabetes needs referred to secondary care?
- Definite or likely type 1 diabetes needs a URGENT referral to secondary care
- Type 2 diabetes is often managed in primary care
- All children need referred or those with low or low normal BMI but NOT urgent
- Patients pregnant or planning pregnancy need referral
- Pre existing renal impairment needs referred
- Other clinical concerns refer
- Consider referral if patient if patient under 40 at diagnosis particularly if strong family history
Blood glucose levels will usually ______ in response to stress or illness
rise
High creatinine can indicate….
kidney damage
What are the potential macrovascular complications of diabetes?
Stroke, MI, peripheral vascular disease, atherosclerosis risk all increased in diabetics but these conditions are not specific to diabetics.
What are the potential microvascular complications of diabetes more specific to diabetes?
Eye disease- retinopathy, cataracts, maculopathy, blurring, glaucoma
Nephropathy
Neuropathy- peripheral, proximal, autonomic
What are the eye complications with diabetes?
Retinopathy (most common) Maculopathy and macular oedema Earlier development of cataracts Glaucoma Visual Blurriness caused by acute hyperglycaemia
How can you reduce the risk of eye complications in those with diabetes?
Annual screening for all low risk diabetics helps identify those who need referred to the eye clinic
What happens in diabetic kidney disease?
Progressive kidney disease caused by damage to the capillaries in the kidney’s glomeruli
Explain the earliest evidence of nephropathy in diabetics?
Microalbuminuria- amounts of albumin so small it is undetectable by standard dipsticks so either need radi-immunoassay or special dipsticks
What is microalbuminuria a predictive marker of?
Progression to nephropathy in type 1 and CV risk in type 2
Microalbuminuria may after some years progress to intermittent ____1___ followed by persistent ___2__
At stage of ____3________ the plasma creatinine is normal but ________4___________
1) albuminuria
2) proteinuria
3) persistent proteinuria
4) only 5-10 yrs off end stage kidney disease in the average patient
In relation to kidney complications all diabetics should have ________________
urinary albumin concentration and serum creatinine measured at diagnosis and at regular intervals usually annually.
1st line treatment for patients with any evidence of nephropathy e.g. microalbuminuria
ACE inhibitors (if intolerant can give an ARB)
3 types of neuropathy in diabetics?
Peripheral
Proximal
Autonomic
Most common type of neuropathy in diabetics?
Peripheral
Describe symptoms of peripheral neuropathy?
numbness, tingling, burning, sharp pains, cramps, loss of balance and coordination
Complications of peripheral neuropathy?
Painless trauma, foot ulcers and Charcot foot
What is charcot foot? Treatment?
weakening of bones in foot, foot changes shape, hot and swollen, need to treat with no weight bearing or air cast boot.
What can painful peripheral neuropathy be treated with?
Atypical pain killers- amitriptyline, gabapentin, pregabalin, capsaicin cream
Describe proximal diabetic neuropathy?
In form of diabetic amyotrophy, much rarer, painful usually asymmetrical wasting of quads, often resolves in time
Autonomic neuropathy most commonly effects what? How does it effect this?
The gut
Gastroparesis (delayed stomach emptying) results in symptoms of nausea, vomiting, bloating and loss of appetite, then get further BG issues due to abnormal food digestion
Treatment of gastroparesis?
Advice- eat little and often Promotility drugs Anti nausea drugs NSAIDS if abdo pain IN extreme cases can paralyse the pylorus with both or insert a gastric pacemaker
Explain problems with sweating in diabetes?
Due to autonomic neuropathy
May get gustatory sweating (sweat a lot after eating)
Periods of anhidrosis followed by hyperhidrosis
Describe problems with autonomic neuropathy that effect the heart?
Postural hypotension
Persistently high HR risk of sudden cardiac death
Things associated with type 1 diabetes?
First five decades
Big peak at school age
Genetic susceptibility and HLA types
Associated with other organ specific auto immune diseases such as thyroid, coeliacs, Addison’s and pernicious anaemia.
What other auto immune diseases are associated with type 1 diabetes?
Thyroid, coeliacs, Addisions and pernicious anaemia
Antibodies for type 1 diabetes?
GAD, ZnT8 and IA-2
Type 1 presentation?
Triad: polydipsia, polyuria and polyphalgia (increased appetite)
Usually acute onset of symptoms: DKA weight loss severe polyuria and polydipsia, fatigue and weakness.
What are the three main groups of insulin treatment?
Rapid acting/ short acting
Intermediate/ long acting
Mixtures
Describe the rapid/ short acting insulins?
Short acting soluble human insulin is older and takes 30 mins to take effect so need 30 mins before meal
Rapid acting analogue insulin has immediate action and is newer. It acts for slightly less time than human soluble.
Difference between human and analogue insulin?
Analogue is genetically altered to have more rapid acting and uniform effect
Describe the intermediate/ long acting insulin?
Intermediate isophane human is older and has a shorter duration of action and more fluctuations than long acting analogues.
Describe insulin mixtures?
These contain short acting or rapid mixed with an intermediate or long acting
What insulin regime is suitable for most adults and allows flexibility?
A multiple injection regimen with a short acting insulin and a longer acting insulin as this allows you to change meal time doses accordingly so can eat and exercise when you want.
If on a twice daily insulin regimen you need to have a ….
fixed diet and exercise timetable
Describe an insulin pump? What are the disadvantages?
Insulin pumps are another option, continuous short acting insulin is delivered by a pump around the waist. Mealtime doses can be programmed and choose different settings.
Disadvantages of insulin pumps are nuisance of being attached to a gadget, skin infections, risk of ketoacidosis if flow of insulin is broken (no protective reservoir) and cost
Route of most insulin? What is it important to do and why?
Subcutaneous injection. It is important to rotate sites to reduce risk of lipohypertrophy- rotate between abdomen, arm and thigh.
Some complications of insulin therapy?
lipohypertrophy, scarring, weight gain, hypos
When are people on insulin particularly at risk of hypos?
just before meals, during night and during exercise
Describe ways to evaluate metabolic control in type 1 diabetics?
Finger prick testing- only provides a snapshot so doesn’t always give a full picture
Glycated haemoglobin- HbA1c measures blood glucose over a longer time
Flash glucose and continuous glucose monitoring- really good- tear a device that measures interstitial glucose.
When adjusting insulin doses a decrease or increase of ____ % is usually recommended to begin?
10
Describe basic guidelines for adjusting insulin doses?
Reduce or increase the dose with the previous meal or the previous dose by 10%
What is the legacy effect of type 1 diabetes?
Having tight glycemic control for the first 10 years greatly reduces chances of complications even if you go back to normal after that
What also presents with polydipsia and polyuria but is much rarer than T1DM?
Diabetes Insipidus
Glucose is ___1____ secreted and then ____2__ reabsorbed in the kidney
1) passively
2) actively
What pathway is thought to be responsible for the complications of diabetes and is only activated in raised blood glucose?
Poyol/ Aldose Reductase pathway
Why do you get proteinuria in kidney damage?
Kidneys usually filter but when filter damaged will get proteinuria
What is two times more common in diabetes?
Hypertension
Diabetic neuropathy affects the _______ first
longest
Why does weight loss occur in diabetes?
There is increased lipolysis
Why does Kussmaul breathing occur in diabetes?
Sign of DKA, deep laboured breathing caused by breathing out excess ketone bodies as acetone.
How many calories are needed to treat a hypo?
300-500 cals
1 unit of insulin will roughly bring blood glucose down by ___
3
Normal insulin to carbohydrate is…
1 unit insulin for every 10g of carb
Why should you not give insulin to counter the carbs in alcohol?
Alcohol causes hypos as it inhibits gluconeogenesis so don’t need the insulin, this could push someone into a hypo
What medications should be stopped when diabetic is sick?
Ace inhibitors SGLT2 inhibitors need reviewed Metformin ARBs NSAIDs Diuretics
In a growing baby diabetes in mother increases risk of…. (6 things)
1) congenital malformation
2) prematurity
3) intra-uterine growth retardation
4) macrosomnia
5) polyhydramnios
6) intra-uterine death
Explain how neonatal hypoglycaemia can occur after birth from diabetic mother?
Maternal glucose crosses the placenta but insulin doesn’t so fetal islets hyper secrete to combat maternal levels so when cord is cut get rebound hypo
Management of diabetic women wanting to get pregnant?
pre-pregnancy counselling, good sugar control pre conception, folic acid 5mg (started 3 months before pregnancy) regular eye checks as risk of accelerated retinopathy, in T2 oral anti diabetic medication stopped except metformin which is safe. In high risk start aspirin at 12 weeks.
Why are women more susceptible to developing diabetes in pregnancy?
progesterones and HPL make a pregnant woman more resistant to insulin (in the past this helped when would have low food intake)
What trimester does gestational diabetes usually occur in? Why?
3rd trimester as this is when placenta is growing a lot more so much more HPL is secreted
Management of gestational diabetes during pregnancy?
Most can be managed by lifestyle, some can be given metformin
Management of gestational diabetes after pregnancy?
Need tested 6 weeks after baby with fasting glucose to ensure it has resolved, if not > T2DM likely. Gestational diabetes suggests a pre-diabetic state so need to counsel women about this.
Long term implications of gestational diabetes?
Suggests a pre-diabetic state- they are 50% more likely to develop type 2 diabetes in the next ten years.
Long term control of weight is by which two hormones? How do they work?
Levels in blood increase as more fat is stored
In the brain they tell the brain to alter energy balance and eat less and increase energy burn.
What happens if you have reduced leptin?
The body mimics starvation- you have no appetite control- you are constantly hungry
Does injecting individuals with leptin work to reduce their weight?
Injecting lectin works in individuals who lack leptin
However, the vast majority of obese individuals have high levels of leptin and they have increased leptin resistanc.
leptin _____ hunger
inhibits
Describe the difficulties in weight loss and maintaining it?
It is difficult to lose weight once gained as increased body fat alters brain function. Long term obesity induces brain re-programming
Your brain views the extra weight as normal and dieting as threat to body survival
When lose weight the resting metabolic rate goes down more than expected so you have to eat less to lose more weight.
What is the only approved drug for weight loss? How does it work?
orlistat- lipase inhibitor so 1/3 of fat is excreted in the faeces
3 bariatric surgeries? Restrictive or malabsorptive?
What is done the most?
Gastric band- restrictive
Sleeve gastrectomy- restrictive
Gastric bypass- both
Gastric bypass
NICE guidelines for bariatric surgery?
bariatric surgery should be considered for patients with a BMI of 40 or more, or between 35 and 40 and other significant disease, if all appropriate non-surgical measures have been tried.
What are symptoms of hypoglycaemia? When do they usually develop?
Symptoms usually develop when BG levels fall below 3mmol/L. Sweating tremor and pounding heart beat. Those with long standing diabetes may lose these warning signs “hypoglycaemic unawareness” and are at greater risk of CNS dysfunction. May appear pale, drowsy and detached. Diagnosis made on symptoms and backed by BG measurement.
What is hypoglycaemic unawareness?
When you have had so many hypos you stop getting warning symptoms and don’t realise you are having a hypo which is really dangerous.
Treatment of hypoglycaemia?
Initially glucose 10-20g is given by mouth either in liquid form of as granulated sugar lumps. If necessary this can be repeated after 10-15 mins. Alternatively 2 teaspoons of sugar or 3 lumps. Non-diet versions of lucozade, coca cola, rubens. Hypos causing unconciousness= emergency. 20% IV glucose through large gauge needle. Alternatively glucagon can be given IM.
Management of unconscious hypoglycaemic patient?
20% IV glucose through a large gauge needle. Alternatively glucagon can be given IM.
What is pathogenesis of diabetic ketoacidosis?
State of uncontrolled catabolism associated with insulin deficiency. In absence of insulin hepatic glucose production accelerates and peripheral uptake by tissues such as muscle is reduced. Rising glucose levels lead to an osmotic diuresis, loss of fluid and electrolytes and dehydration. Plasma osmolality increases and renal perfusion decreases. In parallel rapid lipolysis occurs, leading to elevated circulating free fatty acid levels. Free fatty acids converted to acetyl coA then ketone bodies. It is accumulation of ketone bodies which leads to a metabolic acidosis.
DKA is more common in type 1 or 2?
Type 1
Commonest causes of DKA?
Most common is non adherence to insulin/ poor self management skills
Other: newly diagnosed patients, illness, illicit drug and alcohol use
Presentation of DKA?
Hyperventilation (Kussmaul respiration), Nausea, vomiting, abdo pain, some patients are alert but can be confusion in severe cases. Marked dehydration. Smell of ketones on breath.
Biochemical diagnosis of DKA?
Ketonaemia more than 3 mmol/L (or significant ketonuria)
Blood glucose more than 11 mmol/L or known diabetes
Bicarb less than 15 mmol/L or venous pH less than 7.3
Management of DKA?
Replace fluid loss with 0.9% saline
Replace electrolyte losses- potassium
Restore and base balance (usually happens naturally as other treatment given)
Replace deficient insulin (short acting as IV or IM injections) given until patient can eat and drink
Monitor BG
Seek underlying cause
Complications of DKA?
Hypotension
Coma
Cerebral Oedema (more common in children)
ARDs and aspiration pneumonia
Pathogenesis of hyperosmolar hyperglycaemic state?
Severe hyperglycaemia without significant ketosis. Biochemical differences could be due to age meaning the patient becomes more dehydrated more readily and less severe insulin deficiency. Endogenous insulin levels are sufficient to inhibit hepatic ketogenesis but insufficient to inhibit hepatic glucose production.
How does HHS differ from DKA pathogenesis?
HHS- no ketones!
Type 1 or 2 more often for HHS?
Type 2
Who tends to get HHS?
Type 2 diabetics
Patients are often elderly or middle aged and may have previously undiagnosed diabetes. Precipitating factors: glucose rich foods, thiazides, steroids, illness.
Symptoms of HHS?
Dehydration
Stupor
Coma
How do you calculate plasma osmolality?
2 x Na + urea + glucose
Investigations for HHS?
high plasma osmolality
High blood glucose
Management of HHS?
Fluid replacement 0.9% saline
IV insulin only started if fluids not causing fall in BG
Patient should be encouraged to drink when safe
prophylactic LMWH
Complications of HHS?
Higher mortality than DKA (may be related to age of patients)
Cerebral oedema
Central pontine myelitis
Risk of thromboembolic > prophylactic LMWH
Advice for driving in diabetes?
DVLA must know if on insulin or any other drug that can cause hypos
If had more than 2 severe hypos in 12 months (hypos requiring assistance) then can’t drive
Must inform DVLA is complications that could affect driving so retinopathy and neuropathy
Must check BG before driving and every 2 hrs
What type of diabetes is more inherited out of 1 or 2
2
Why do you give IV insulin in DKA?
Subcutaneous route is not good as slow acting and blood flow will be reduced in shocked patients
