Diabetes (T1 & T2) Flashcards
1
Q
Diabetes complications - KNIVES
A
Kidney – nephropathy
Neuromuscular – peripheral neuropathy, mononeuritis, amyotrophy
Infective – UTIs, TB
Vascular – coronary/cerebrovascular/peripheral artery disease
Eye – cataracts, retinopathy
Skin – lipohypertrophy/lipoatrophy, necrobiosis lipoidica
2
Q
Diabetes mellitus is a chronic, multi-system disease, with profound biochemical and structural sequelae. It can be classified into four main groups:
A
Type 1 diabetes mellitus: characterised by an inability to produce/secrete insulin due to autoimmune destruction of the beta-cells (production site of insulin) in the pancreatic islets of Langerhan.
Type 2 diabetes mellitus: characterised by a combination of peripheral insulin resistance and inadequate secretion of insulin. It is strongly associated with obesity and the metabolic syndrome.
Gestational diabetes mellitus: new onset of diabetes in pregnancy. It is associated with both maternal and foetal complications and as such patients are managed as part of a multi-disciplinary team in both antenatal and diabetic clinics. Patients with GDM have a higher risk of developing both GDM in future pregnancies and overt diabetes mellitus.
Other: These can be divided into genetic and acquired disease. Genetic causes refer to monogenic diabetes (i.e caused by mutation to a single gene). They are rare and collectively termed ‘mature-onset diabetes of the young’ (MODY). Acquired causes may be secondary to medications or pathological conditions. Common causes include corticosteroids, pancreatitis and pancreatic tumours.
3
Q
T1DM
A
Type 1 diabetes is a condition caused by an inability to produce or secrete insulin. It is characterised by an absolute insulin deficiency, state of persistent hyperglycaemia with abnormalities in carbohydrate, fat and protein metabolism.
It accounts for 90-95% of diabetes in children, classically presenting with polyuria, polydipsia and weight loss. Insulin is central to management as is monitoring for and treating complications.
4
Q
T1DM
A
The condition can develop at any age. It is estimated that over 370,000 adults are affected with T1DM within the UK and this is thought to represent about 10% of adults who suffer from diabetes. The incidence of T1DM is thought to be increasing.
5
Q
Insulin is produced and secreted by beta cells within the pancreatic islets of ….
A
Insulin is produced and secreted by beta cells within the pancreatic islets of Langerhan.
6
Q
Up to 85% of patients with T1DM are found to have circulating autoantibodies. The … antibody, an enzyme found within beta cells of the pancreas, is most commonly identified.
A
Up to 85% of patients with T1DM are found to have circulating autoantibodies. The anti-glutamic acid decarboxylase (anti-GAD) antibody, an enzyme found within beta cells of the pancreas, is most commonly identified.
7
Q
In T1DM, it is estimated that approximately 15% of patients will have a first-degree relative who has the condition, and there is 30-50% concordance in … twins. There is also a significant link with other autoimmune conditions. The prevalence of T1DM is higher in patients with autoimmune conditions such as Graves’ disease, autoimmune thyroiditis and Addison’s disease.
A
In T1DM, it is estimated that approximately 15% of patients will have a first-degree relative who has the condition, and there is 30-50% concordance in monozygotic twins. There is also a significant link with other autoimmune conditions. The prevalence of T1DM is higher in patients with autoimmune conditions such as Graves’ disease, autoimmune thyroiditis and Addison’s disease.
8
Q
T1DM has also been linked to certain human … …
A
T1DM has also been linked to certain human leucocyte antigens (HLA). HLAs are the human form of the major histocompatibility complex (MHC) proteins key to cell-signalling. In particular, they are important for the immune system to be able to distinguish its own cells from pathogens (e.g. from bacteria).
9
Q
It is estimated that up to 95% of patients with … have human leucocyte antigens HLA-DR3 or HLA-DR4.
A
It is estimated that up to 95% of patients with T1DM have human leucocyte antigens HLA-DR3 or HLA-DR4.
10
Q
Under normal physiological conditions, glucose metabolism is a tightly controlled process maintaining blood glucose levels between … and …
A
Under normal physiological conditions, glucose metabolism is a tightly controlled process maintaining blood glucose levels between 3.5-8.0 mmol/L.
11
Q
Glucose & insulin during fasting
A
In normal fasting conditions, insulin concentrations are low as it acts locally on the liver to modulate glucose production. It does this by modulation of glycogenolysis (breakdown of the stored version of glucose termed glycogen) and gluconeogenesis. The latter describes the formation of glucose from non-carbohydrate carbon substrates including amino acids (alanine and glutamate), lactate and glycerol (derived from fatty acids).
12
Q
Glucose & insulin post-prandial
A
Following a meal (post-prandial), insulin is released from the pancreas in large amounts. The release of insulin is enhanced by the release of other gut hormones including glucagon-like peptide (GLP). Insulin acts on the liver to reduce its glucose output, inhibiting glycogenolysis and gluconeogenesis. Insulin is also essential for the promotion of glucose uptake in peripheral tissues (e.g. muscle and adipose tissue).
In addition to this insulin:
Decreases lipolysis, increases fatty acid and triacylglycerol synthesis.
Increases glucose uptake in adipose tissue and muscle.
Increases protein synthesis in a variety of tissues and prevents protein degradation.
13
Q
In addition to this insulin:
A
Decreases lipolysis, increases fatty acid and triacylglycerol synthesis.
Increases glucose uptake in adipose tissue and muscle.
Increases protein synthesis in a variety of tissues and prevents protein degradation.
14
Q
Counter-regulatory hormones
A
Counter-regulatory hormones include glucagon, adrenaline, growth hormone and cortisol. These hormones promote glucose production within the liver (e.g. glycogenolysis, glyconeogenesis) and inhibit peripheral uptake of glucose.
15
Q
In patients with T1DM, the destruction of …-cells leads to the progressive reduction in insulin secretion.
A
In patients with T1DM, the destruction of beta-cells leads to the progressive reduction in insulin secretion.
16
Q
The absence of insulin leads to an increase in the rate of glucose production from the liver and reduced peripheral uptake of glucose. This is exacerbated by the high levels of glucagon and other counter-regulatory hormones. This results in an osmotic diuresis leading to …(4)
A
The absence of insulin leads to an increase in the rate of glucose production from the liver and reduced peripheral uptake of glucose. This is exacerbated by the high levels of glucagon and other counter-regulatory hormones. This results in an osmotic diuresis leading to polyuria, polydipsia, dehydration and electrolyte derangement.
17
Q
Why do T1DM patients lose weight?
A
The peripheral tissue is unable uptake glucose to utilise it as energy. Weight loss occurs secondary to fluid loss and increased muscle and fat breakdown.
18
Q
The development of ketosis leads to… … (diabetic ketoacidosis). High circulating ketones can induce vomiting, further exacerbating dehydration and electrolyte derangement.
A
The development of ketosis leads to metabolic acidosis (diabetic ketoacidosis). High circulating ketones can induce vomiting, further exacerbating dehydration and electrolyte derangement.
19
Q
LADA - what is this?
A
Latent-onset autoimmune diabetes in adults (LADA) refers to a variant of T1DM that occur later in life.
It refers to a group of patients who have autoimmune destruction of beta cells (as evidenced by positive autoantibodies). It tends to have a gradual onset.
20
Q
LADA diagnosis
A
It can be suspected in patients who develop diabetes in adult life with associated ketosis, weight loss, low BMI and family history of autoimmune disease. Patients are frequently diagnosed with T2DM whose initial treatments will be ineffectual. Like other cases of T1DM, insulin therapy is required.
21
Q
The majority of patients will develop T1DM in childhood or adolescence with features of … (4)
A
The majority of patients will develop T1DM in childhood or adolescence with features of lethargy, polyuria, polydipsia and weight loss.
22
Q
Symptoms of T1DM (4)
A
Polyuria & polydipsia
Weight loss
Vomiting
Lethargy
23
Q
Signs of T1DM(2)
A
Mild-moderate dehydration (dry skin, dry mucous membranes, reduced skin turgor)
BMI < 25
24
Q
Signs and symptoms of …
A
T1DM
25
Diabetic ketoacidosis - signs and sy,proms
```
Confusion
Moderate-severe dehydration (sunken eyes, prolonged capillary refill time)
Vomiting +/- diarrhoea
Abdominal pain
Decreased urine output
Reduced GCS
Coma
Shock (tachycardia, hypotension)
Kussmaul breathing (Deep sighing respiration)
```
26
```
Confusion
Moderate-severe dehydration (sunken eyes, prolonged capillary refill time)
Vomiting +/- diarrhoea
Abdominal pain
Decreased urine output
Reduced GCS
Coma
Shock (tachycardia, hypotension)
Kussmaul breathing (Deep sighing respiration)
```
Signs of?
DKA
27
Signs and symptoms of …
DKA
28
The majority of patients with T1DM will be children or adolescents but the diagnosis should not be discounted in adults (…).
The majority of patients with T1DM will be children or adolescents but the diagnosis should not be discounted in adults (LADA).
29
Patients with suspected T1DM should be…
Patients with suspected T1DM should be referred the same day to a specialist diabetic team for further assessment to confirm the diagnosis and start immediate management.
30
Further investigations should be reserved for patients presenting diabetic … (FBC, UE, CRP, LFT, ABG etc) or where … or MODY are suspected (e.g. c-peptide, genetic testing).
Further investigations should be reserved for patients presenting diabetic ketoacidosis (FBC, UE, CRP, LFT, ABG etc) or where LADA or MODY are suspected (e.g. c-peptide, genetic testing).
31
Management of T1DM requires …
Management of T1DM requires life-long exogenous insulin to prevent acute complications (e.g. DKA) and long-term sequelae (e.g CKD, IHD, Retinopathy).
32
In clinical practice, there are three main insulin regimes that are used in patients with T1DM:
Basal-bolus regime: typically involves the use of rapid- or short-acting insulin before meals and a long-acting preparation for basal requirements. This regime is thought to best mimic the physiological function of the pancreas in response to meals and provides better flexibility in control of blood glucose. It is the standard approach for patients newly diagnosed with T1DM.
One, two, or three injections per day regime: traditionally a biphasic regime with the use of both short-acting and intermediate-acting insulin as separate injections or a mixed product.
Continuous insulin infusion via a pump: supplies rapid- or short-acting insulin. It may be used in patients who are experiencing troubling hypoglycaemic episodes with multiple daily injections regimes.
33
Basal-bolus regime:
Basal-bolus regime: typically involves the use of rapid- or short-acting insulin before meals and a long-acting preparation for basal requirements. This regime is thought to best mimic the physiological function of the pancreas in response to meals and provides better flexibility in control of blood glucose. It is the standard approach for patients newly diagnosed with T1DM.
34
One, two, or three injections per day regime:
One, two, or three injections per day regime: traditionally a biphasic regime with the use of both short-acting and intermediate-acting insulin as separate injections or a mixed product.
35
Continuous insulin infusion via a pump:
Continuous insulin infusion via a pump: supplies rapid- or short-acting insulin. It may be used in patients who are experiencing troubling hypoglycaemic episodes with multiple daily injections regimes.
36
Insulin regimes T1DM options (3)
37
All patients with T1DM are advised to monitor their own blood sugars at least …
All patients with T1DM are advised to monitor their own blood sugars at least four times a day (e.g. three times before meals and once before bed). There may be times when blood glucose monitoring is recommended more frequently including sporting activities, pregnancy and in those with hypoglycaemic episodes.
38
The main targets are detailed below: (T1DM)
On waking: fasting blood glucose 5–7 mmol/L
Before meals: blood glucose 4–7 mmol/L
Post meals: test after 90 minutes, blood glucose 5–9 mmol/L
39
Long term T1DM control
Long-term control is monitored with HbA1c. This blood test is a measure of glycated haemoglobin, indicative of the average blood glucose over 3 months. It should be repeated every 3-6 months to assess glycemic control.
Patients and clinicians should target a HbA1c < 48 mmol/L (6.5%). Factors that may demand a higher threshold include hypoglycaemic episodes, occupation and co-morbidities.
40
Patients and clinicians should target a HbA1c < …. mmol/L (6.5%). Factors that may demand a higher threshold include hypoglycaemic episodes, occupation and co-morbidities.
Patients and clinicians should target a HbA1c < 48 mmol/L (6.5%). Factors that may demand a higher threshold include hypoglycaemic episodes, occupation and co-morbidities.
41
Monitoring for complications - T1DM
A regular diabetic assessment looking at all aspects of care, including surveillance for complications, is essential for all patients to improve morbidity and mortality.
On an annual basis (more frequently if required), patients should receive a diabetic review. This includes assessment of injection site problems, retinopathy, nephropathy, diabetic foot problems (e.g. neuropathic problems), cardiovascular risk factors and thyroid disease.
42
Screening in T1DM
Retinopathy: annual screening
Nephropathy: renal function (eGFR) and albumin:creatinine ratio (ACR)
Diabetic foot problems: full examination including footwear, monofilament assessment of neuropathy, vascular assessment +/- dopplers.
Cardiovascular risk factors: primary/secondary prevention strategy with optimisation of blood pressure, lipids, weight, smoking and others
Thyroid disease: screening blood test
43
Education - T1DM
Education
The Dose Adjustment For Normal Eating (DAFNE) programme is aimed at providing type 1 diabetic patients with a way of calculating the amount of carbohydrate in each meal to adjust their insulin accordingly.
44
Honeymoon period - T1DM
The honeymoon period can occur in newly diagnosed patients in whom there is residual beta cell function.
This may negate the need for exogenous insulin for a period. The honeymoon period can last for weeks to months before a deterioration in glycemic control and the need for exogenous insulin.
45
‘Sick-day rules’ refer to a number of recommendations in T1DM with an intercurrent illness. Advice includes: (5)
Continue insulin therapy, alterations may be required, advice from a specialist may be sought
Increase frequency of blood glucose monitoring
Consider ketone monitoring
Maintain good hydration and when possible a normal meal pattern, meals may be replaced by carbohydrate based drinks
Seek urgent medical attention if unable to tolerate oral intake, drowsy or sustained vomiting
46
The two main acute diabetic complications seen in patients with T1DM are …
The two main acute diabetic complications seen in patients with T1DM are hypoglycaemia and diabetic ketoacidosis.
47
Microvascular complications - T1DM
Uncontrolled diabetes results in small vessel disease affecting the kidneys, nerves and retinas (amongst other systems).
48
Uncontrolled diabetes results in small vessel disease affecting the kidneys, nerves and …(amongst other systems).
Uncontrolled diabetes results in small vessel disease affecting the kidneys, nerves and retinas (amongst other systems).
49
… … is one of the major eye-related disorders that can occur in patients with diabetes. More than 95% of patients will have detectable changes after 20 years. Other disorders include cataracts and ocular palsies.
Diabetic retinopathy is one of the major eye-related disorders that can occur in patients with diabetes. More than 95% of patients will have detectable changes after 20 years. Other disorders include cataracts and ocular palsies.
50
Retinopathy - T1DM
Persistent damage to the retina leads to areas of ischaemia and release of angiogenic factors such as vascular endothelial growth factor (VEGF). This promotes new formation of vessels that are weak and friable. This leads to complications including haemorrhage, fibrosis and retinal detachment.
51
Non-proliferative: Retinopathy
Non-proliferative:
Background (R1): dot and blot haemorrhages, hard exudates, cotton wool spots
Pre-proliferative (R2): intraretinal microvascular abnormalities (IRMA), venous beading
52
Proliferative retinopathy
Proliferative:
| Proliferative (R3): new vessels at the disc and elsewhere (NVD, NVE), fibrosis, traction retinal detachmen
53
Maculopathy - retinopathy
Maculopathy: exudates, oedema, NVE
54
Good glycemic control and regular screening to assess early changes are key to preventing and managing disease. … is used to manage proliferative disease. The aim of this is to burn holes within the ischaemic retina to prevent the release angiogenesis factors (e.g. VEGF), which stimulate new vessel formation.
Good glycemic control and regular screening to assess early changes are key to preventing and managing disease. Photocoagulation is used to manage proliferative disease. The aim of photocoagulation is to burn holes within the ischaemic retina to prevent the release angiogenesis factors (e.g. VEGF), which stimulate new vessel formation.
55
Diabetic nephropathy usually develops 15-25 years following the onset of diabetes and can progress to …
Diabetic nephropathy usually develops 15-25 years following the onset of diabetes and can progress to end-stage renal disease (ESRD).
56
The earliest sign of diabetic nephropathy is the presence of …., which can be assessed with an albumin:creatinine ratio (ACR).
The earliest sign of diabetic nephropathy is the presence of microalbuminuria, which can be assessed with an albumin:creatinine ratio (ACR). An ACR 3 - 30 mg/mmol is suggestive of microalbuminuria, now categorised as moderately increased albuminuria.
57
The earliest sign of diabetic nephropathy is the presence of microalbuminuria, which can be assessed with an albumin:creatinine ratio (ACR). An ACR 3 - 30 mg/mmol is suggestive of microalbuminuria, now categorised as moderately increased albuminuria.
A1: < 3 mg/mmol, normal or mild increase
A2: 3 - 30 mg/mmol, moderately increased
A3: > 30 mg/mmol, severely increased
58
Microalbuminuria is a marker of systemic microvascular damage and patients should be treated with an…
Microalbuminuria is a marker of systemic microvascular damage and patients should be treated with an ACE inhibitor even in the presence of normotension. Chronic kidney disease (CKD) in diabetes is evidenced by a persistently low eGFR < 60 mmol/L and/or an ACR persistently > 3 mg/mmol/L.
59
n. Chronic kidney disease (CKD) in diabetes is evidenced by a persistently low eGFR < 60 mmol/L and/or an ACR persistently > … mg/mmol/L.
n. Chronic kidney disease (CKD) in diabetes is evidenced by a persistently low eGFR < 60 mmol/L and/or an ACR persistently > 3 mg/mmol/L.
60
The main types of diabetic neuropathy are listed below. (4)
Symmetrical polyneuropathy: typically a peripheral neuropathy that occurs in the leg secondary to loss of vibration, pain and temperature sensation.
Mononeuropathy: damage to a single cranial or peripheral nerve (e.g. third nerve palsy).
Diabetic amyotrophy: a spectrum of disease affecting the lumbosacral plexus leading to symmetrical pain, weakness and wasting in the proximal muscles of the leg.
Autonomic neuropathy: a spectrum of conditions related to damage of the autonomic nervous system, which can effect multiple systems.
61
Diabetic foot
Diabetic foot problems refer to a wide range of pathologies that are thought to occur secondary to the combination of peripheral neuropathy and poor vascular supply.
62
Diabetic foot
Due to loss of sensation and poor blood supply, patients are at risk of a number of complications including diabetic ulcers, secondary infection (e.g. cellulitis, osteomyelitis), skin necrosis and eventually amputation.
63
Diabetic foot - Charcot’s joint
Another well-known problem is Charcot’s joint. This is a complex neuropathic arthropathy that results from loss of sensation and subsequent repeated micro-trauma to the foot (traditionally the mid-foot). Microtrauma in the presence of poor peripheral blood flow leads to remodelling, swelling and distortion of the whole joint.
64
Foot ulcer - diabetic patients
It is estimated that 10-15% of diabetic patients will develop a foot ulcer during their illness and approximately 50% of diabetic hospital admissions are related to diabetic ulcers and foot problems. The management of diabetic foot disease is essential to help recognise and treat complications early. There are now recognised diabetic foot services that are available to help manage patients with these conditions.
65
Diabetes is a significant risk factor for … and related macrovascular complications.
Diabetes is a significant risk factor for atherosclerosis and related macrovascular complications.
66
Optimisation of cardiovascular risk factors on an annual basis is essential to prevent premature cardiovascular disease. This involves: (4)
Smoking cessation
Nutritional support & exercise
Consideration of anti-lipid therapy (e.g. atorvastatin)
Blood pressure control (e.g. ACE inhibitor)
67
… refers to a group of metabolic disorders that result from an inability to produce and/or reduced sensitivity to insulin.
Diabetes mellitus refers to a group of metabolic disorders that result from an inability to produce and/or reduced sensitivity to insulin.
68
T2DM is a complex, polygenic disease that is strongly associated with ...
T2DM is a complex, polygenic disease that is strongly associated with obesity.
69
T2DM has been shown to have a genetic basis. The risk of developing the condition is as high as 75% if both parents have suffered from the condition. Moreover, in … twins, there is a 50-90% concordance for developing the condition.
T2DM has been shown to have a genetic basis. The risk of developing the condition is as high as 75% if both parents have suffered from the condition. Moreover, in monozygotic twins, there is a 50-90% concordance for developing the condition.
70
Importantly, T2DM is considered a … disease with numerous genetic variants contributing to overall disease risk. Certain ethnicities (e.g. Asian/African) have a 2-4x increased risk of developing the condition.
Importantly, T2DM is considered a polygenic disease with numerous genetic variants contributing to overall disease risk. Certain ethnicities (e.g. Asian/African) have a 2-4x increased risk of developing the condition.
71
Environmental risk factors have a significant impact on the development of T2DM. Obesity and inactivity account for the majority of this risk (80-85%). Obesity is associated with insulin resistance and the metabolic syndrome.
Other major environmental risk factors include: (5)
```
Poor dietary habit (low fibre, high glycemic index diet)
Low birth weight
Medications
Polycystic ovarian syndrome
History of GDM
```
72
The two principle mechanisms involved in the development of T2DM are peripheral insulin resistance and inadequate insulin secretion.
It has long stood that peripheral insulin resistance was at the centre of T2DM. The importance of reduced insulin secretion and beta-cell dysfunction in the pathophysiology is now acknowledged.
73
During normal control of glucose homeostasis, the release of insulin following ingestion of a meal leads to the uptake of glucose into cells (peripheral muscle).
Insulin is able to bind to insulin receptors on the cell surface. Binding leads to a number of downstream responses including effects on lipid metabolism, protein metabolism and cellular growth. In general, these are anabolic effects that:
Inhibit proteolysis and lipolysis
Inhibit hepatic gluconeogenesis
Promotes hepatic glycogen synthesis
74
Activation of the insulin receptor also initiates translocation of the glucose receptor GLUT-… (found in the cytosol of adipose and striated muscle) to the cell surface. This allows movement of glucose intracellularly.
Activation of the insulin receptor also initiates translocation of the glucose receptor GLUT-4 (found in the cytosol of adipose and striated muscle) to the cell surface. This allows movement of glucose intracellularly.
75
As hyperglycaemia develops, the beta cells within the Islets of Langerhans must secrete more insulin to deal with the increase in glucose leading to hyperinsulinaemia. These high levels of insulin are still inadequate to restore glucose homeostasis. It is thought that high glucose levels (and lipids) are toxic to beta cells leading to a depletion in their cellular mass. This is termed …. During autopsy, patients with T2DM have shown to have deposition of amyloid within islet cells supporting the idea of beta cell depletion.
As hyperglycaemia develops, the beta cells within the Islets of Langerhans must secrete more insulin to deal with the increase in glucose leading to hyperinsulinaemia. These high levels of insulin are still inadequate to restore glucose homeostasis. It is thought that high glucose levels (and lipids) are toxic to beta cells leading to a depletion in their cellular mass. This is termed glucotoxicity. During autopsy, patients with T2DM have shown to have deposition of amyloid within islet cells supporting the idea of beta cell depletion.
76
Clinical features of T2DM
Patients may complain of lethargy, polyuria, polydipsia, weight loss, and recurrent infections (e.g. thrush, balanitis) or be picked up on routine testing.
77
Diagnosis of T2DM
The major diagnostic tool in T2DM is the measurement of glycated haemoglobin (HbA1c).
78
HbA1c (glycated haemoglobin) is measured in the blood and reflects the average blood glucose concentration over a … month period (the average survival time of an erythrocyte). Glycated haemoglobin occurs due to non-enzymatic irreversible modification of the beta globin chain in haemoglobin. As blood glucose levels increase the amount of glycation of haemoglobin also increases.
HbA1c (glycated haemoglobin) is measured in the blood and reflects the average blood glucose concentration over a three month period (the average survival time of an erythrocyte). Glycated haemoglobin occurs due to non-enzymatic irreversible modification of the beta globin chain in haemoglobin. As blood glucose levels increase the amount of glycation of haemoglobin also increases.
79
In general, the diagnosis of diabetes is made if the level of HbA1c is ≥ … mmol/mol (6.5%), which correlates with an average blood glucose level of 7.8 mmol/L. Patients with a level between 42-47 mmol/mol (6-6.4%) are at risk of developing diabetes and said to be ‘pre-diabetic’. Importantly, the use of HbA1c as a diagnostic tool is dependent on whether the patient is symptomatic.
In general, the diagnosis of diabetes is made if the level of HbA1c is ≥ 48 mmol/mol (6.5%), which correlates with an average blood glucose level of 7.8 mmol/L. Patients with a level between 42-47 mmol/mol (6-6.4%) are at risk of developing diabetes and said to be ‘pre-diabetic’. Importantly, the use of HbA1c as a diagnostic tool is dependent on whether the patient is symptomatic.
80
Patients with a level between … mmol/mol (6-6.4%) are at risk of developing diabetes and said to be ‘pre-diabetic’. Importantly, the use of HbA1c as a diagnostic tool is dependent on whether the patient is symptomatic.
Patients with a level between 42-47 mmol/mol (6-6.4%) are at risk of developing diabetes and said to be ‘pre-diabetic’. Importantly, the use of HbA1c as a diagnostic tool is dependent on whether the patient is symptomatic.
81
If the patient is symptomatic (e.g. thirst, polyuria), then a single HbA1c reading of … mmol/mol or greater is enough to confirm the diagnosis. If the patient is asymptomatic, the diagnosis should be based on two abnormal readings (either two HbA1c readings, or one HbA1c reading and an additional test such as fasting glucose levels).
If the patient is symptomatic (e.g. thirst, polyuria), then a single HbA1c reading of 48 mmol/mol or greater is enough to confirm the diagnosis. If the patient is asymptomatic, the diagnosis should be based on two abnormal readings (either two HbA1c readings, or one HbA1c reading and an additional test such as fasting glucose levels).
82
There are some situations in which HbA1c should be used with caution due to other co-morbidities. In general, conditions interrupting … (e.g. EPO use, iron-deficiency), haemoglobin structure (e.g. haemoglobinopathies), .. (e.g. CKD, alcoholism), or red cell survival (e.g. haemolysis, splenectomy) will effect the level of HbA1c. In these situations, the HbA1c should be used with caution or an alternative test used (e.g. fasting glucose).
There are some situations in which HbA1c should be used with caution due to other co-morbidities. In general, conditions interrupting erythropoiesis (e.g. EPO use, iron-deficiency), haemoglobin structure (e.g. haemoglobinopathies), glycation (e.g. CKD, alcoholism), or red cell survival (e.g. haemolysis, splenectomy) will effect the level of HbA1c. In these situations, the HbA1c should be used with caution or an alternative test used (e.g. fasting glucose).
83
Normal fasting glucose levels should be approximately …
Normal fasting glucose levels should be approximately 4-6 mmol/L.
84
Fasting plasma glucose levels
The diagnosis of diabetes can be made if the fasting glucose levels are ≥ 7 mmol/L on two separate readings in a patient who is asymptomatic or a single reading if the patient is symptomatic. As discussed above, ‘two readings’ may be two fasting glucose measurements or one fasting glucose measurement and one HbA1c.
Patients with a fasting glucose level between 6-6.9 mmol/L are said to have impaired fasting glucose (IFG), which is a marker of pre-diabetes and increases the risk of developing overt diabetes.
85
Patients with a fasting glucose level between …/L are said to have impaired fasting glucose (IFG), which is a marker of pre-diabetes and increases the risk of developing overt diabetes.
Patients with a fasting glucose level between 6-6.9 mmol/L are said to have impaired fasting glucose (IFG), which is a marker of pre-diabetes and increases the risk of developing overt diabetes.
86
A random blood glucose level ≥ … mmol/L is indicative of diabetes. This measurement is not currently used in the diagnosis of the condition.
Patients with a high random plasma glucose should be assessed for potential complications (e.g. HHS, DKA) and concurrent illness. Concurrent illnesses can increase plasma glucose levels as part of the normal physiological stress response. Patients with high levels should undergo further testing (e.g. HbA1c or fasting glucose levels).
A random blood glucose level ≥ 11.1 mmol/L is indicative of diabetes. This measurement is not currently used in the diagnosis of the condition.
Patients with a high random plasma glucose should be assessed for potential complications (e.g. HHS, DKA) and concurrent illness. Concurrent illnesses can increase plasma glucose levels as part of the normal physiological stress response. Patients with high levels should undergo further testing (e.g. HbA1c or fasting glucose levels).
87
Oral glucose tolerance test
The oral glucose tolerance test (OGTT) measures the ability of the body to deal with a glucose load over a two hour period. Its use has largely been replaced by HbA1c in clinical practice.
The OGTT firstly involves the patient fasting (usually overnight). A glucose measurement can then be taken at time 0 hrs. The patient is then given a 75 g glucose load. Traditionally, a blood sample for glucose is then taken at 2 hours. Levels greater than 11 mmol/L at 2 hours are suggestive of diabetes. Levels ≥ 7.8 mmol/L but < 11.1 mmol/L are suggestive of impaired glucose tolerance (IGT).
The OGTT is usually reserved for assessment of gestational diabetes. It should be noted that NICE produced updated guidelines on the diagnosis of gestational diabetes where the values for diagnosis are set much lower than in non-pregnant patients.
88
Management - T2DM
The management of T2DM requires education, lifestyle changes, medications and the monitoring of complications.
89
Lifestyle advice - T2DM
Lifestyle modifications may be the earliest changes instigated in patients with or at risk of developing diabetes (e.g. HbA1c 42-47 mmol/mol). It is essential that these modifications continue once antidiabetic medications are introduced. Lifestyle advice can help patients achieve sustained weight loss, better physical fitness, improved diet and ultimately improved glycaemic control.
90
Lifestyle advice - T2DM
Patients should be encouraged to maintain a healthy balanced diet with plenty of fibre, low-index carbohydrate and controlling the intake of high-fat foods. In those with excess body weight, dietary plans can help with weight loss, targeted plans may be appropriate.
Exercise can lower blood glucose levels as it increases glucose use by muscles. Patients should be informed about the UK physical fitness guidelines and encouraged to exercise daily with at least 150 minutes of moderate intensity activity over a weekly period.
Patients should be encouraged to reduce alcohol consumption and stop smoking. Alcohol increases weight and may exacerbate or prolong hypoglycaemia induced by antidiabetic medications. Smoking cessation advice should be made available and offered to all patients with T2DM.
91
Exercise - T2DM
Exercise can lower blood glucose levels as it increases glucose use by muscles. Patients should be informed about the UK physical fitness guidelines and encouraged to exercise daily with at least 150 minutes of moderate intensity activity over a weekly period.
92
Alcohol and smoking - T2DM
Patients should be encouraged to reduce alcohol consumption and stop smoking. Alcohol increases weight and may exacerbate or prolong hypoglycaemia induced by antidiabetic medications. Smoking cessation advice should be made available and offered to all patients with T2DM.
93
Antidiabetic drugs T2DM
Metformin is one of the most commonly used medications in T2DM. Metformin is a biguanide, which lowers blood glucose levels through inhibition of hepatic gluconeogenesis whilst increasing peripheral insulin sensitivity and enhancing peripheral uptake of glucose. All patients with T2DM should be started on metformin unless contraindicated (e.g. CKD, those at risk of lactic acidosis, poorly tolerated).
94
Metformin is a …, which lowers blood glucose levels through inhibition of hepatic gluconeogenesis whilst increasing peripheral insulin sensitivity and enhancing peripheral uptake of glucose. All patients with T2DM should be started on metformin unless contraindicated (e.g. CKD, those at risk of lactic acidosis, poorly tolerated).
Metformin is a biguanide, which lowers blood glucose levels through inhibition of hepatic gluconeogenesis whilst increasing peripheral insulin sensitivity and enhancing peripheral uptake of glucose. All patients with T2DM should be started on metformin unless contraindicated (e.g. CKD, those at risk of lactic acidosis, poorly tolerated).
95
All patients with T2DM should be started on metformin unless contraindicated - list these
e.g. CKD, those at risk of lactic acidosis, poorly tolerated
96
Step 1 T2DM management
Standard release metformin
Aim for HbA1c < 48 mmol/mol, increasing dose as needed
Monitor renal function, consider modified-release preparations if develop adverse GI effects
97
Step 2 T2DM management
Consider dual antidiabetic therapy if HbA1c rises > 58 mmol/L
Metformin in combination with a second antidiabetic agent:
Sulfonylurea (SU)
Dipeptidyl peptidase-4 inhibitor (DPP-4i)
Pioglitazone
Sodium–glucose cotransporter 2 inhibitor (SGLT-2i)
Aim for HbA1c < 53 mmol/mol
98
Step 3 - T2DM treatment
Step 3 - Consider dual antidiabetic therapy if HbA1c rises > 58 mmol/L
Metformin in combination with a second antidiabetic agent:
Sulfonylurea (SU)
Dipeptidyl peptidase-4 inhibitor (DPP-4i)
Pioglitazone
Sodium–glucose cotransporter 2 inhibitor (SGLT-2i)
Aim for HbA1c < 53 mmol/mol
99
Step 4 T2DM management
In patients on triple antidiabetic therapy and ongoing poor glucose control, consider further intensification
Consider combination treatment with metformin, SU and glucagon-like peptide-1 (GLP-1) mimetic
It should be noted there are strict criteria for the use of a GLP-1 analogue and patients must achieve certain glycemic and weight targets to warrant continuing the medication
If already on an insulin-based regime, seek specialist advice
100
If metformin is contraindicated an alternative treatment ladder is used.
101
Insulin-based regimens - T2DM
The use of insulin should be considered early in the management of patients with T2DM. It is usually considered in patents with poor glycemic control despite dual antidiabetic with metformin and another agent.
Insulin therapy may not be appropriate for those at significant risk of hypoglycaemia, a personal preference against insulin or concerns relating to licensing for driving group 2 vehicles. Obese patients may find insulin may exacerbate weight issues, its use should be avoided where possible.
102
Insulin therapy should be initiated by healthcare professionals experienced with the use of insulin. There are a number of insulin regimes that may be used in patients with T2DM:
Once or twice daily intermediate-acting insulin (NPH)
Intermediate-acting insulin along-side a short-acting insulin as separate injections or a pre-mixed formula
Once daily long-acting insulin therapy (glargine, determir)
Basal-bolus regimes
103
In general, patients are offered an intermediate-acting insulin therapy such as NPH in the initial stages. If glycemic control is particularly bad (e.g. HbA1c > 75 mmol/L) patients may be started on mixed insulin (intermediate and short-acting). Long-acting insulin is usually reserved for patients where hypoglycaemia is a problem with NPH insulin or the patients rely on carers for help with their injections. Finally, patients on a pre-mixed insulin regime that still have inadequate blood glucose control should be assessed for conversion to a basal bolus regime.
In general, patients are offered an intermediate-acting insulin therapy such as NPH in the initial stages. If glycemic control is particularly bad (e.g. HbA1c > 75 mmol/L) patients may be started on mixed insulin (intermediate and short-acting). Long-acting insulin is usually reserved for patients where hypoglycaemia is a problem with NPH insulin or the patients rely on carers for help with their injections. Finally, patients on a pre-mixed insulin regime that still have inadequate blood glucose control should be assessed for conversion to a basal bolus regime.
104
Treatment targets for patients with T2DM are largely based on serial measurements of HbA1c.
Patients with poor glycaemic control require measurement of the HbA1c every 3 months. Patients with stable disease can have their HbA1c measured every 6 months.
The main treatment targets are shown below:
The main treatment targets are shown below:
Management with lifestyle modifications only: aim HbA1c < 48 mmol/mol
Management with lifestyle and a single antidiabetic agent: aim HbA1c < 48 mmol/mol
Management with a drug associated with hypoglycaemia (e.g. SU): aim HbA1c < 53 mmol/mol
Management with higher intensification regimes: aim HbA1c < 53 mmol/mol
105
If HbA1c levels are not adequately controlled by a single drug and rise to ≥ 58 mmol/mol, then intensification of medical therapy should be considered. Additionally, reinforcement about dietary advice, lifestyle changes, adherence to medical treatment should be completed to support patients in achieving a HbA1c < … mmol/mol.
If HbA1c levels are not adequately controlled by a single drug and rise to ≥ 58 mmol/mol, then intensification of medical therapy should be considered. Additionally, reinforcement about dietary advice, lifestyle changes, adherence to medical treatment should be completed to support patients in achieving a HbA1c < 53 mmol/mol.
106
Finally, on annual basis patients should be screened for major complications of diabetes:
Retinopathy: annual retinal screening and eye check
Nephropathy: renal function (eGFR) and albumin:creatinine ratio (ACR)
Neuropathy and diabetic foot: assessment for peripheral neuropathy, autonomic neuropathy, full examination including footwear, monofilament assessment of neuropathy, vascular assessment +/- dopplers.
Cardiovascular risk factors: primary/secondary prevention strategy with optimisation of blood pressure and lipids.
107
Every …-…., patients should have their HbA1c checked and management changed according
Every 3-6 months, patients should have their HbA1c checked and management changed accordingl
108
The two major acute diabetic complications seen in patients with T2DM are …
The two major acute diabetic complications seen in patients with T2DM are hypoglycaemia and hyperosmolar hyperglycaemic state (HHS).
109
T2DM - HHS vs DKA?
It is worth noting that some patients with T2DM are also at risk of developing diabetic ketoacidosis (DKA) due to beta cell dysfunction and a lack of insulin secretion. Patients presenting unwell with type 2 diabetes mellitus should be assessed for DKA (e.g. urinary/plasma ketone levels, pH and bicarbonate) and treated accordingly. Both HHS and DKA are associated with significant mortality if not treated promptly and the reasons for developing these conditions should be explored with the patient during admission (i.e. non-adherence to treatment, intercurrent illness).
110
T2DM - eyes
Diabetic retinopathy is one of the major eye-related disorders that can occur in patients with diabetes. More than 95% of patients will have detectable changes after 20 years. Other disorders include cataracts and ocular palsies. When diagnosed with T2DM, GPs should immediately refer for eye screening.
111
… … is one of the most common causes of chronic and end-stage kidney disease.
Diabetic nephropathy is one of the most common causes of chronic and end-stage kidney disease.
112
Additional considerations are now recommended for the prescription of sodium-glucose transport protein 2 (SGLT2) inhibitors to patients with T2DM and CKD:
Additional considerations are now recommended for the prescription of sodium-glucose transport protein 2 (SGLT2) inhibitors to patients with T2DM and CKD:
Consider an SGLT2 if ACR 3-30 mg/mmol
Offer an SGLT2 if ACR > 30 mg/mmol
