Diabetes complications start at pre-diabetes blood sugar levels

Adapted from Steve Freed’s article in Diabetes in Control Spring 2020

Elevated blood glucose levels indicative of prediabetes appear to be associated with increased risks for retinopathy, peripheral neuropathy, and also diabetic nephropathy, according to Emanuelsson et al. (p.894).

As a result, they suggest that screening for micro- and macrovascular complications should be recommended for individuals with raised blood glucose or prediabetes.

In total, about 820,000 individuals were considered in the analysis. The authors found that, on an observational level, increasing glucose levels were associated with higher risks for both micro and macrovascular complications. Validation in the cohorts further confirmed the associations with retinopathy, neuropathy, nephropathy, and myocardial infarction but not peripheral arterial disease or kidney disease. This risk is present at glucose levels within what is currently considered the normal or prediabetic range.  

The American Diabetes Association recommends screening for prediabetes in adults with obesity or overweight and with risk factors for diabetes. However, this screening does not include examinations for microvascular complications.

Screening for retinopathy, neuropathy, diabetic nephropathy and additional risk factors such as obesity, hyperlipidemia, and hypertension might be indicated in individuals with prediabetes. 

The finding of a stepwise increase in the risk of vascular disease with increasing glucose levels within the normoglycemic range or higher support the idea that an elevated glucose level has a causal role in the pathogenesis of the microvascular disease, as do levels below the diabetes cut off. This is in line with the general understanding of the natural history of type 2 diabetes as a continuous process of declining β-cell function and increasing relative insulin deficiency, leading to a continuous increase in glucose that is initiated years before the diabetes threshold is reached.

Randomized controlled trials have shown that lifestyle changes and treatment with glucose-lowering drugs can reduce the progression from prediabetes to diabetes.

Recent 30-year follow-up data from a study of 577 Chinese individuals showed that lifestyle interventions in individuals with prediabetes reduce long-term risks of diabetes, a composite of microvascular complications, cardiovascular disease, cardiovascular mortality, and all-cause mortality.

The effects of lifestyle intervention are not likely to be due to glucose-lowering alone but to several beneficial metabolic effects. The findings highlight the importance of early detection of glycemia and screening for prediabetes in asymptomatic individuals through the use of risk assessment tools—such as the one currently provided by the American Diabetes Association  


  • Having blood glucose in the prediabetes range considered normal has shown to begin the complications of diabetes much earlier than thought. 
  • We need to be more proactive at the first signs of prediabetes. That means any fasting glucose reading above 100mg (5.5 mmol/l) or a random reading of above 139mg/dL(7.8 mmol/l). 
  • These findings suggest that elevated glucose levels should be identified as an essential risk factor for micro- and macrovascular disease in the general population and that screening for microvascular disease may be recommended, along with screening for additional cardiovascular risk factors, in individuals with prediabetes. 
  • Maybe it is time to just call prediabetes, diabetes, which would provide for much earlier treatment. 

Reference for “Prediabetes Equals Diabetes”:

Diabetes Care 2020 Apr; 43(4): 894-902.https://doi.org/10.2337/dc19-1850 

What if that amputation wasn’t necessary?

Expert advisers thought that 7.3% of the cases they reviewed had had unnecessary amputations. Revascularisation or conservative management was thought to have been more appropriate.

The National Confidential Enquiry in to Patient Outcome and Death looked at 479 cases in England and Wales in 2014.  They considered that only 44% of patients who had amputations for vascular or diabetes had received care in accordance with recommended standards published in the Vascular Society’s Quality Improvement Framework for Major Amputation Surgery.

Amputations can become necessary for a variety of reasons: severe trauma, sudden artery blockage, or sudden overwhelming infection for instance.  But for many diabetic and vascular patients the damage is insidious, and treatment to reverse damage can be effective if done early enough.  At the end of months or years of unsuccessful interventions sometimes amputation gives relief from unrelenting pain or infection, mobility can be restored, and a better quality of life can begin again.

The UK mortality rates for people undergoing the operations was 12.4% compared to the USA’s 9.6% for a similar group of patients.

A major problem was that the co-ordinated multi-disciplinary care that is needed to divert patients away from amputation and for successful rehabilitation after amputation is not always in place. A Leeds vascular consultant, Michael Gough said, “patients need treatment of diabetes and heart problems, physiotherapy, rehabilitation and a properly planned discharge”.

In my own area, the multi-disciplinary teams are not in place to reliably prevent amputations nor to give smooth discharge home and rehabilitation afterwards. It is bad enough to struggle at home after an amputation but truly devastating to think that something far less final could have been attempted.

Based on BMJ article by Susan Mayor 15 Nov 2014.

Forthcoming Drug Recommendations for Type 2 Diabetics from NICE

NICE have some drug recommendations to make for diabetics in their forthcoming guidelines later this year. It can be seen that NICE are heavily influenced by drug costs. So what could these new guidelines mean for you?

The blood pressure recommendations have scarcely changed but the use of Repaglinide first or second line for blood sugar control is a change from previously. Blood sugar targets have tightened up a bit and structured education is expected for insulin users. Cheaper, older insulins are favoured. Blood sugar testing is being rationed considerably. Aspirin is out of favour but drugs for erectile dysfunction are in. Erythromycin is being adopted for the very difficult to manage problem of gastroparesis.

The medications you will need to take to improve your life with diabetes will depend on many factors. Primarily, what do you want a medication to do for you?

The answer to this will depend on how well you are managing lifestyle changes, how long you have had the condition, the presence of any complications, and how tight you want glycaemic control, blood pressure and lipids to be. The targets need to be individualised to you, and this can be done by becoming more informed about your condition and discussing it with other health care providers and people with diabetes. We discuss these factors in our book, the Diabetes Diet, and I will be updating you on some of the new recommendations in further articles.

This article covers the changes to blood pressure medications, glycaemic targets and drugs to control blood sugar, self-monitoring of blood sugar, insulin initiation and the management of complications.

Blood pressure

For diabetics the BP target is 140/80 if there are no blood vessel complications such as kidney, eye or cerebrovascular disorders. If these are present the target is 130/80. BP lowering can improve peripheral neuropathy as well as stroke, MI, blindness and renal failure. 25% of those with type 2 diabetes develop nephropathy within 20 years of diagnosis.

Because ACE inhibitors and sartans reduce progression to renal disease better than other classes of anti-hypertensive agent they should be used first in diabetics unless they are a woman who could get pregnant as this class of drug is teratogenic. First line for women in this situation is a Calcium channel blocker CCB instead.

For Afro-Caribbean use ACE + diuretic or ACE + Calcium channel blocker. This is because this group respond less well to ACEs and sartans so should have add on drugs right from the start.

For those who can’t tolerate an ACE use a sartan unless there is renal deterioration or hyperkalaemia.

If BP is still not controlled add a CCB or thiazide diuretic.

If still not controlled use any of an alpha blocker e.g. Doxasozin or a beta blocker e.g. Bisoprolol or potassium sparing diuretic e.g. Spironolactone.

If someone has already had a heart attack or heart failure they will probably be on a beta blocker anyway. Carvedilol was superior to metoprolol in metabolic terms for renal protection in one study.

Use spironolactone with caution if someone is already on a sartan or ACE because they all can raise potassium.

Glycaemic control


All-cause mortality rises as hbaic rises and decreases as hbaic reduces. The risk of microvascular complications increase over hba1c of 6.5% (48 mmol/mol) or 7% (53) for macrovascular complications. Fasting blood glucose levels influence MI but not stroke or angina.  Amputation rates rise over the age of 60 for any given hbaic. Therefore it can be seen that to improve life expectancy and the quality of life that in general the tighter the blood sugar control the better.  At the same time doctors are asked to adopt an individualised approach to blood sugar targets and consider life expectancy, personal preferences, co-morbidities, risks of polypharmacy and they should consider stopping ineffective drugs.


NICE felt they could not comment on hba1c under 6% because only one study they looked at achieved this. Hba1cs in the 4s or 5s are not uncommon in low carbing diabetics however so don’t let this put you off your stride. NICE do say that if adults reach a lower blood sugar target than they were expecting and are not having hypoglycaemia the doctor should encourage them to maintain it.

They suggest:

6.5% for non-drug using diabetics or on drugs that don’t cause hypos e.g. metformin, pioglitazone, gliptins, victoza.

7% for the rest e.g. repaglinide, sulphonylureas, insulin.

7.5% intensify treatment, but individual circumstances e.g. life expectancy, co-morbidities, hypos need to be taken into account.

Drug step-laddering:

The first step for most diabetics is to offer metformin as the initial drug treatment.  But don’t give or stop metformin if the kidney test, the egfr is below 30 and use with caution if under 45. Regular metformin can give diarrhoea and if this is a problem the long acting version can be used.

If there is symptomatic hyperglycaemia, such as thirst and weight loss consider a sulphonylurea or insulin first. Other drugs may be considered once the blood sugars have stabilised. .

Next they suggest Repaglinide on its own or with metformin. Repaglinide is not licenced with other drugs. For people who could not tolerate metformin and repaglinide are the most cost effective treatment option.

If repaglinide was not suitable or is not achieving the desired blood sugar target any of pioglitazone, a sulphonylurea or a gliptin can be used.  The choice can be tailored to the patient.

Sulphonylureas had the most hypos and gliptins the least. Metformin had the best weight loss. Sulphonylurea and Pioglitazone had the most weight gain. NICE prefer doctors to use the lowest cost gliptin because they are relatively expensive.

Reducing hypoglycaemia should be a particular aim for those on insulin or a sulphonylurea. As blood sugar monitoring is necessary for these drugs, this factor can increase the cost considerably over and above the costs of the medication.

Consider GLP1 mimetic i.e. Byetta or Victoza if the BMI is over 35.  Only continue it if hba1c goes down by 1% and weight goes down by 3% over six months.

Insulin is considered to be the “last option”. There is currently research being carried out on the effects of early use of insulin in type two diabetes and this may change practice in the future.

Only offer insulin + Victoza in specialist care setting.

Insulin initiation

When starting insulin use support from an appropriately trained health professional and give:

Structured education

Telephone support

Frequent self monitoring

Dose titration to target

Dietary understanding

Hypoglycaemia management

Management of acute rises in blood sugar

Continue metformin

The usual first choice insulin is NPH insulin at bedtime or twice daily.

The more expensive Lantus or Levemir may be considered if a carer would be able to cut to once daily injections or if hypoglycaemia is a problem or otherwise the patient would need twice daily NPH and oral drugs or they can’t use the NPH device.

If hbaic is 9% (75) consider twice daily pre-mixed bi-phasic insulin.

Blood sugar testing

NICE recommends that self- monitoring of blood sugars is to be avoided unless a person is on insulin, has symptomatic hypoglycaemia, or oral medication that causes hypos or driving or operating machinery, pregnant or trying for a baby.  It may be worth considering if a patient is on oral or intravenous steroids.

Doctors or nurses should reassess the need for self monitoring annually to see if it remains worthwhile.

Self monitoring produced only a 0.22% reduction in hbaic. It was considered by NICE to be not helpful for most people with type two diabetes though more hypos were detected with it.


Anti-platelet therapy for cardiovascular protection

There is no overall benefit to taking aspirin or clopidogrel in type 2 diabetes unless they already have cardiovascular disease.

Managing complications

Autonomic neuropathy symptoms are: gastroparesis, diarrhoea, faecal incontinence, erectile dysfunction, bladder disturbance, orthostatic hypotension, gustatory and other sweating disorders, dry feet and ankle oedema.

Treatments for gastroparesis are metoclopramide, domperidone and erythromycin.

Refer to a specialist if severe or persistent vomiting occurs or the diagnosis is in doubt.

Nocturnal diarrhoea may indicate autonomic neuropathy.

Tricyclics are often given for neuropathic pain but can increase postural hypotension.

Erectile dysfunction

Offer men the chance to speak about this at their annual review. Offer Viagra, Cialis and similar and refer if these don’t work.

Eye damage

Diabetic eye damage is the single largest cause of blindness before old age.

Refer to the emergency ophthalmologist if:

Sudden loss of vision

Rubeus’s Iridis

Pre-retinal or vitreous haemorrhage

Retinal detachment

Send for rapid review if there is new vessel formation.

So what do you think of the new NICE recommendations?  Do you think these changes will affect your medications?