Control of type 2 diabetes
David Kinshuck,
Pat
Lamb,
Urmila Griffiths
Embrace your diabetes

Enlarge Haemoglobin, in your blood, joins
up with glucose to form the chemical called HbA1c
We are learning more about diabetes all the time, and it is becoming
clear the harder you work to control your diabetes when it is diagnosed
the more benefit you will get in the long term. Complications from diabetes
will be prevented or delayed.
Type 2 diabetes is a progressive condition. It is not a 'mild' form
of diabetes. The exercise you take and the food you eat need to balance
the remaining natural insulin your body makes. This page is designed
to give readers an idea how decisions are made concerning their care,
but remember every patient is different and advice can vary.
Take control....learning how to control type 2 diabetes
Your diabetes nurse can teach you the basics, and reading up is helpful.
But there are structured diabetes education programs that your doctor must enable you to attend such a course. The programs teach you how to take control of type 2 diabetes, and patients
who have attended the program have better diabetic control and fewer problems.
What is happening in type 2 diabetes
There are four particular problems.
These factors work together to contribute to type 2 diabetes. The factors
may be controlled by genes. So your children
or brothers and sisters may be affected, and they should take precautions
(exercise, healthy diet, not becoming overweight, and not smoking). Social issues such as conflict/homeless contribute BMJ 18.
First, there is a shortage of insulin
You may have inherited this condition from your parents. Alternatively, a
few people may have had pancreatitis or a bad attack of mumps that damages
the pancreas.
The shortage of insulin is due to damage to the islets in the pancreas where
your insulin is made.
The pancreas is a gland is behind your stomach, and throughout its tissue
are these tiny groups of cells called islets. It is these islets that make your
insulin, and they release the insulin into your blood stream, just as it is
needed. In this type of diabetes the islets become damaged and effectively
'dry up'.
This process may be the main cause of your diabetes if you are not overweight,
have always had a healthy diet, and have always taken exercise.
Second, there is insulin resistance.
Normally the insulin is released by the pancreas into the blood stream. The
insulin circulates to muscle cells, where it acts as a 'door opener' and lets
the glucose into the cell. The muscle cell uses it for energy.
However, in this type of diabetes the muscles and other tissues are much
less responsive to insulin. This means the pancreas has to produce more insulin
for the same effect.
This poor response to insulin is called 'insulin
resistance'. Insulin resistance develops if you are overweight or take
too little exercise, and especially if you are overweight and take too
exercise.
Losing weight and exercise (90 minutes walking
a day for example) both lower the insulin resistance. With less insulin resistance,
you need less insulin for the same effect, and so the insulin that your beta
cells make (or that you inject) will go further. The amount of 'resistance'
varies according to how much fat there is.
So if you are overweight, your pancreas has to produce considerably more insulin
for the same effect, versus someone who is not overweight. If you can lose
weight, the responsiveness to insulin will increase, your insulin will have
a much greater effect, and your diabetes will be easier to control.
In practice this means that unless you lower your 'insulin resistance' your
pancreas is even more likely to 'run out of insulin' and you may need insulin
injections sooner, and if you
are fatty tissue actually becomes deposited in your pancreas, and
this damages the pancreas even more.
At the beginning, the resistance to insulin makes the pancreas compensate
by producing more insulin, but eventually it cannot produce enough. Joslin. Type 2 is progressive: the pancreas produces less insulin each year, more treatment and eventually insulin is often needed. However, this process is a lot slower with regular exercise, a healthy diet, and keeping thin.
Third, there are genes
Genes linked to diabetes work in different ways. Some genes may not cause
diabetes directly, but make you overeat and become overweight, and the excess
weight causes the diabetes. One gene may make people fidget, and fidgeters
are less likely to become overweight. Finally, there are many genes that
may cause diabetes. These include MODY genes
and haemochromatosis.
It is often worth having an iron
test for haemochromatosis, as early diagnosis will help your relations
(iron binding capacity and serum ferritin tests?).
Fourth, stress
Stress increases the risk of heart
disease, and probably diabetes itself also.
Fifth, inflammation
These factors to cause a low grade inflammation/ oxidative stress. BMJ
2011, and this causes more damage.
Sixth, sleep
Sleep difficulties (sleep apnoea) is common, and makes control of the diabetes difficult.
These factors combine to cause type 2 diabetes
there is a 50% risk of becoming diabetic if you
are overweight and exercise very little. (After Williams & Pickup.) Sleep apnoea plays a role also.
These risks combine, as opposite:
risks increase with a combination of factors
Excellent
article.
Pattern of progression
- At the beginning of type 2 diabetes, a healthy diet may be sufficient
to lower the sugar and keep the HbA1c below 48mmol/mol / 6.5% IFCC-HbA1c
- Later, metformin is needed.
- Later still, add exanatide/Liraglutide if overweight or other drug if thin.
- Later still insulin may be required
Slowing down progression
Exercise and losing weight (if overweight) dramatically slow
this progression rate down, and even prevent diabetes in some people.
Exercise reduces the dose of insulin needed (BMJ
2011). If you are on a diet (without
drugs or insulin: diet controlled diabetes), and your HbA1c is 42mmol/l / 6% this is
an ideal level. But if the HbA1c rises to 64mmol/l / 8%, you need to eat less (if you
are overweight) or may need tablets, so you should see your GP or nurse. See
weight below.
Similarly, if you are on one set of tablets, and your HbA1c is 42mmol/l / 6%, you are
controlled. But if it is 64mmol/l / 8% , you need to eat less (especially if you are overweight)
or go on more tablets, or possibly insulin. See 'Exercise
in diabetes'. Your doctor and diabetic specialist nurse will need to advise
you if your HbA1C is higher than 53mmol/mol / 7%.
Testing you sugar/glucose level
Test your glucose and aim
for
- fasting 4 - 7 mmol/l (when wake up)
- 4 - 7 mmol/l before meals
- 5-9 2 hours after a meal
- 4 - 7 mmol/l 4 hours after a meal and other times
- fasting 5 - 7 mmol/l insulin users
If you want to know whether or not your diabetes is controlled, your doctor
can check your HbA1c level. But you should test your own glucose level testing.
If you 'embrace' your diabetes, you will gradually learn to control it and
achieve an HbA1c of 48mmol/mol / 6.5%. or below (slightly higher if you have had diabetes a long time). But to do this, you need to check test your
glucose:
Test
- now and again if not using insulin and well controlled
- test at different times each time you test
- test much more often if you are trying to improve your control
- 4-6 times a day if using multiple dose insulin
- remember, you still need tablets if you are ill; if you are being sick
or cannot swallow the tablets, let your doctor or nurse know.
- If well you need to increase medication until well controlled, as advised
by your doctor/nurse
- Accept higher levels if you are very ill
- ketones can be present (although they are more common in type 1 diabetes) BMJ 2013
Do you need tablets (or insulin), and if so what? A treatment plan
Once your sugar levels start to rise despite exercise and the best diet you
can stick to, you need tablets. Similarly, if you are on tablets and your sugar
levels start to rise, you need a higher dose, or an extra tablet, or need insulin.
Here is a protocol as to what you may need, from here. All
patients should generally start with metformin: all other drugs lower the HbA1c
equally, but with different 'side' effects/effects on weight etc (JAMA
2010).
Type 2 diabetes: a treatment plan (separate page).
this plan is probably out of date, but your diabetic team will hvae an upto date plan NICE
0-8
weeks, if levels higher than HbA1c 48 mmol/mol / 6.5% at onset of diabetes if well

add Metformin
increase to 2.0 - 2.5gm over 3 months (divided doses)

0-8
weeks, if levels higher than HbA1c 48 mmol/mol / 6.5% .
this is the target for recently diagnosed patients

if
low weight |
if
overweight |
- Sitagliptin & Linaglyptin (Trajenta) do not cause weight gain, but all the other treatments
below increase weight
- Linaglyptin (Trajenta) if renal function reduced
- If thin, sulphonylurea and titrate to maximum dose depending on response.
Eg gliclazide. start 40-80 mg daily. 160 mg
as a single dose, with breakfast; higher doses divided; max. 320 mg daily. Weight will increase. Sulphonylurea do cause hypos.
- Dapagliflozin (Farxiga) if well
- or add insulin as below
These drugs (and only one of this list would normally be added) will
only lower the HbA1c 0.5-1.0%.
Therefore
if the HbA1c is >8.5% 69mmol/l, a 7.5% /58mmol/ltarget will not be reached, so insulin
may be best. However, a gradual HbA1c drop may be best in retinopathy
patients. |
Incretins
Reduced renal function
|
12
weeks, if levels higher than target (>HbA1c 48 mmol/mol / 6.5% at onset)
Add insulin
- NICE
- Add bedtime basal insulin eg degludec
- adjust dose to achieve fasting
blood glucose 4-7mmol/l slowly over several weeks
- Continue treatment with metformin, continue exentatide (licensed 2012), stop other glucose lowering
drugs
- this is reviewed here
(NEJM)
- Insulin will cause weight gain..consider bariatric surgery
if very overweight

12
weeks, if levels higher than target
- Add rapid acting insulin prior to meals (basal
bolus).
- Continue metformin
- infirm/very elderly/poor compliance convert to twice daily insulin mixture +/- metformin, consider degludec
- twice daily Levemir/detemir is easier to adjust than Lantus/glargine, and would be my reommendation for well motivated patients, especially those taking regular exercise such as a round of golf (less insulin will be needed on golfing days).
- aim for lower HbA1c is well motivated patients, perhaps 6.5%,
if insulin not needed
- aim for HbA1c <58 mmol/mol / 7.5% if using insulin
- lipids....usually a statin is helpful
to lower cholesterol in most patients;
- a fibrate is
preferable if triglycerides high
- exercise 60 minutes
a day, 120 minutes if overweight...any exercise, such as walking, swimming, cycling, gardening
- losing weight if overweight
is critical..overweight patients should be advised about a diet and
lose a pound a week..prognosis is significantly improved
- low
blood pressure needed
- patients should be taught to monitor their own blood sugar and should
attend a diabetes education program
- for insulin patients taking lots of exercise on some days, or who are well but have lots of hypos, a pump might be helpful.
- why do insulin users gain weight..Joslin
Metformin
Metformin helps
in diabetes as it allows glucose to enter your body's tissues where it is used
for energy etc. It makes the tissues more responsive to insulin, and this lowers
the sugar levels (this is 'lowering insulin resistance'). Benefits NEJM
2008.
As a result, in addition to the lower blood sugar levels, you may lose weight.

- Insulin
resistance in type 2 diabetes: insulin has reduced effect on muscles cells,
so each muscle cell cannot absorb the glucose. The glucose stays in the
blood where it reaches high levels which are harmful.
- Metformin
acts on muscles to allow glucose to enter and be utilised. Blood glucose
levels drop and you may lose weight.
- Metformin starting dose is 500mg twice/day, increasing to 1gm twice/day. There
is a slow release form that can be used once daily.
- Side effects may include nausea (feeling sick), diarrhoea,
loss of appetite, and the presence of a metallic taste in your mouth.
These usually occur when treatment is first started, when the dose is increased,
or when metformin is taken in high doses (greater than 2,500 mg per day).
To avoid these side effects, take metformin with meals. Also, when treatment
is first started, your doctor should prescribe a low dose and slowly increase
the dose over a few weeks. If you experience frequent diarrhoea, ask your doctor
about lowering the dose of metformin, which may help. With continuous use,
these side effects usually subside within one month. For details see www.diabetes.org
- There are other rare side effects. Contact your doctor if you become ill.
It is still safe if your kidneys are damaged, although there is a small risk
of acidosis. It
is probably safe in heart failure.
- Metformin NEJM 2012 in type 2 younger people.
Gliclazide
This
is one of many 'sulphonylureas' There are many others. (Glipizide is another.)
These drugs act on the pancreas to make it release more insulin. Side-effects
are generally mild and include feeling sick, bowel changes, headache, and
weight gain.
Dose: initially, 40-80 mg daily, adjusted according to response; up to 160
mg as a single dose, with breakfast; higher doses divided; max. 320 mg daily.
Ideally gliclazide is taken 30 minutes before a meal.
Sulphonylureas contribute to hypoglycaemic episodes. Gliptins are more expensive, but have few side effects and far fewer hypos. They probably should be considered second line after metformin.
- Exenatide (Byetta) & Liraglutide (Victoza)
- Exenatide weekly (Bydureon)
Exenatide
(Byetta) & Liraglutide
(Victoza) are new drugs that
lower glucose levels and aid weight loss. Details. NICE BMJ. 2012.
This group of drugs, given by injection, probably should be considered third line if the HbA1c is not too high, as it will only be lowered 10-20mmol/l / 1-2%. So an ideal patient for this group of drugs will have an HbA1c of ~75mmol/l / 9.0%, already be using metformin and a gliptin.
- Once daily Victoza (Liraglutide) or
twice daily Byetta / Exenatide BMJ. or weekly Bydureon.
- They are GLP-1 analogues. Glucagon-like peptide-1 (GLP-1)
is a naturally occurring peptide hormone, released from the gut after eating.
GLP-1 stimulates insulin release, reduces glucagon
release (this stops the liver making glucose), delays stomach emptying, and
stops hunger feelings. (BMJ)
- do not cause hypos...so frequent glucose monitoring is not required
- lower HbA1c 10 mmol/l / 10%.
- if the HbA1c is 86mmol/l / 10% it will lower it to 75mmol/l / 9.0%, but would not achieve a target
of ~53mmol/mol / 7% needed to keep your ophthalmologist happy.
- it does help weight loss...about 7lb for each of the first 2 years.
- the main side common effect is nausea/sickness, but many patients
prefer to stay on them
- they are second line in type 2 diabetes, if overweight, in addition to
metformin.
- they are added to metformin.
- generally they reduce the rise in glucose with meals, not the basal
glucose.
- they should not be used in conjunction with a sulphonylurea or glitazone
(sulphonylurea or glitazones are no longer ideal for overweight patients
as they always increase weight ..Exenatide/Liraglutide are best). Sulphonylurea/glitazones
are stopped if Exenatide started.
- see Tips
for Patients
- avoid
- if patient thin, BMI <25,
- previous pancreatitis or alcohol abuse: the main rare side effect is
pancreatitis;
- avoid
if heart failure/risk of fracture
- avoid if there is reduced kidney function: GFR <30
- Care if GFR 30-50
- Here are some example patients..licenced use, in addition to metformin
- Patient overweight, HbA1c 64mmmol/l / 8%, using metformin, add Exenatide ...expect
HbA1c 53mol/l / 7%, some weight loss. In such patients Exenatide is used instead
of starting insulin.
- Patient overweight, HbA1c 75 mmmol/l / 9%, using metformin, add Exenatide...expect
HbA1c 64 mmmol/l / 8%, some weight loss, control not ideal.
- There are new versions of this drug that can be used once a week, and they
can reduce heart problems etc. 2011
Exenatide (Byetta) and insulin use
- it is very useful in addition to insulin
and metformin.
- Patient HbA1c 75mmol/l / 9%, using metformin,
very overweight, large insulin dose (e.g. >100units/day). Can halve
the dose of insulin, add Exenatide, will reduce weight, perhaps a few
stone (HbA1c may drop a little, but will not achieve 53mmol/mol / 7%. Generally reduce
the pre-meal boluses i.e. rapid acting. By adding Exenatide and reducing
insulin dose, patients will lose weight.
- Hypos are possible if using insulin.
- Once the weight is reduced a little, and the insulin dose reduced, consider
bariatric surgery to lower the HbA1c further.
- 1% risk of pancreatititis
Exenatide weekly (Bydureon)
- a once weekly subcutaneous injection..likely to become very popular
- if you have type 2 diabetes and are overweight and have an HbA1c64-75 mmmol/l / 8.0-9.0, this is the drug for you see
- 1% risk of pancreatititis
Gliptins...DPP4 (dipeptyl peptidase-4 inhibitors)
Sitagliptin (Januvia)
- Sitagliptin is
a DPP-4 inhibitors, 100mg once day.
It can be used in addition to metformin, glitazone, or sulphonylurea, lowering
the HbA1c 0.7-1.0%%. See: "Sitagliptin
reduces blood glucose concentrations by enhancing the effects of ‘incretins’.
Incretins are hormones (chemicals) which are produced by the gut (bowel) in
response to food. These drugs are therefore also known as ‘incretin enhancers’." Lowers HbA1c 10mmol/l / 0.7-1%~.
- Side effects are uncommon. Nausea, flatulence has been reported. When combined
with glitazones swelling of the feet may be seen. As with some other oral blood
glucose lowering drugs, hypoglycaemia may occur.
- It is not suitable with
type 1 diabetes, previous diabetic ketoacidosis, see. Reduce the dose if renal function reduced. (details) GFR 60-30 50mg; GFR <30 25mg. Combination with metformin Janumet usually bd.
Linaglyptin (Trajenta)
- Linaglyptin works in a similar way to Sitagliptin above, but is is safe in reduced renal function. (It is excreted in the liver not the kidney.) It is
also a DPP-4 inhibitors.
SGLT2 inhibitors Dapagliflozin (Farxiga)
- see; see; long term success DOM15
- IJEM 16 "There are subsets of subjects with type 2 diabetes who may have insulin deficiency, beta cell autoimmunity, or prone to diabetic ketoacidosis. In these subjects, SGLT2 inhibitors should be used with caution to prevent the rare risks of ketoacidosis."
- not ideal if patient is using diuretics
- need good kidney function..GFR (kidney function >60 (%))
- not suitable if pregnant
- If HbA1c 64mmol/l (8%) should drop to 7%, (53mmol/mol)
- If HbA1c 75 to 58mmol/l (9) should drop to 58mmol/l (7.5%)
- NICE 14
- works by increasing glucose in urine
- more likely to get genito urinary fungal infections
- canagliflozin versus sitagliptin see 15
- related drug Empagliflozin
- lowers Hba1c about 10mmols/l (0.8%) if not on insulin, 5mmols/l (0.5% if on insulin)
- http://www.patient.co.uk/medicine/dapagliflozin-tablets-forxiga
- canagliflozin
- linked to slightly increased risk of amputations, more thrush and urinary tract infections, and osteoporosis. Rarely, acute kidney injury.
- carefully monitor patients receiving canagliflozin who have risk factors for amputation, such as poor control of diabetes and problems with the heart and blood vessels
- consider stopping canagliflozin if patients develop foot complications such as infection, skin ulcers, osteomyelitis, or gangrene
- advise patients receiving any sodium-glucose co-transporter 2 (SGLT2) inhibitor about the importance of routine preventive foot care and adequate hydration
- continue to follow standard treatment guidelines for routine preventive foot care for people with diabetes
If you need insulin, what type
- If you are a type 2 diabetic and are starting insulin for the first time,
a basal insulin such as once daily degludec . NICE

If overweight you need to weigh yourself each week or even more often and lose weight slowly
Weight and bariatric surgery
As mentioned type 2 diabetes is partly caused by resistance or
lack of responsiveness to insulin. This resistance depends on the amount of
body fat. The lower your weight, the less insulin resistance there is,
and the less insulin you need (whether your natural or injected), and the better
the control of the diabetes. If you cannot lose weight, it is important not
to put weight on.
Remember, certain foods are very 'fattening' and you do not need them to be
healthy: red meat, full fat dairy food like cheese, butter, cream, and cakes.
See diet and weight. Find
out if you overweight.
Insulin seems to make most people put weight on. Diet and exercise becomes
even more important; a Levemir/detemir basal-bolus
regime is said to reduce the weight gain considerably. Exenatide as above
can reduce weight, and it can now be used in addition to insulin (there will be less weight gain and often weight reduction, and less insulin is needed).
Expert individual advice from a dietician can
be very helpful. Bariatric surgery can be better than conventional therapy NEJM 2012 2012 if obese. There are risks, such as 13% need additional surgery, but it can be very effective.
Exercise
Exercise is very important in diabetes. As well as helping your heart, it helps to lose
weight. Walking, swimming, or dancing help a great deal. If you are disabled,
a physiotherapist, expert gym instructor, your doctor, or your nurse might
be able to suggest gentle exercises you can do.
Start gently, such as a minute every half hour, or 10 minutes 3 times a day.
If you are exercising, or cannot, and are unable to lose weight, you must
be eating too much. Most people in this situation eat more meat than they should,
or have cakes at weekends, or indulge in some way. We are not saying 'stop'
this, but it is your choice, but if you are interested in good health then
losing weight is important.
If you are struggling to lose weight
- Eating more meat than the size of one a weetabix will prevent you losing
weight. Fish too is fattening, so again, try and stick to an amount slightly less that
the size of one a weetabix.
- Plan your menu here.
The size of portions is absolutely crucial, see here.
- If you are hungry, you can eat almost as many vegetables and fruits as
you wish. Naturally five bananas a day is fattening, but generally you will
not put weight on.
- A side salad included in lunch and supper will be helpful, although best
without much mayonnaise. If you use mayonnaise or oil, use small amounts.
Small amounts of fat as vegetable fats as olive or sunflower oil are essential
as part of your diet. A strictly no fat diet is very harmful. On the
other hand, animal fat is not essential, and more than a small amount is
harmful. See the diet page for help.
- If you eat to much and cannot reduce what you eat, BMI >40, consider bariatric
surgery.
- discussed BMJ 2011

simvastatin protects the heart
Cholesterol, HDL, triglyceride
Lipids are discussed in more detail here; Low lipid
levels prevent/slow down retinopathy and all other diabetic complications HPS . Fibrates low
triglycerides, statins lower cholesterol. Diet and exercise lower both.
Typical medication
Typical
medications for someone with type 2 diabetes in 2014, not severe enough
to require insulin
- metformin
- gliclazide (an alternative as above if overweight)
- a statin for cholesterol
- an ACE or A2RB inhibitor for high blood pressure
- another blood pressure tablet
- possible a fibrate & aspirin
As you will have read above life has not become easier if you have type 2
diabetes. We know a lot more, and there is a lot more patients and professionals
can do. On the positive side the health of patients is a lot better. We will have to wait many years before we can say goodbye to all the tablets
though.