Complications

Complications table
ComplicationTimeframeLikelihood

diabetic ketoacidosis (DKA)

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DKA is the classical acute complication of type 1 diabetes, characterised by a biochemical triad of hyperglycaemia, ketonaemia, and metabolic acidosis, with rapid symptom onset. The most common precipitants are missed insulin injections or physiological stresses such as infection or myocardial infarction.

Work-up (e.g., ECG, search for infection) is indicated to detect precipitating factors. In the setting of insulin deficiency, stress hormones including glucagon, cortisol, and catecholamines raise blood glucose levels and stimulate ketogenesis.

Hyperglycaemia and ketosis cause osmotic diuresis leading to dehydration.

Symptoms tend to be due to dehydration and metabolic acidosis and include dry mouth, hyperventilation, abdominal pain, nausea, vomiting, and reduced consciousness.

Blood glucose and ketone levels are high and there is an anion gap metabolic acidosis.

Treatment involves rapid hydration, insulin infusion, and correction of electrolyte imbalance. Hourly monitoring of blood glucose and ketones, and regular monitoring of bicarbonate, potassium, and pH is required. Insulin infusion must continue until DKA has resolved and the patient is eating and drinking. Switch from insulin infusion to subcutaneous insulin when DKA is resolved.

Hyperkalaemia is common but hypokalaemia is an indicator of severe DKA.

Treatment with bicarbonate is not indicated except when venous blood pH is <6.9 and after discussion with a senior consultant.[134]

hypoglycaemia

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Hypoglycaemia is the most common and potentially most serious side effect of insulin therapy. It can lead to decreased quality of life; severe hypoglycaemia is a medical emergency which can cause confusion, seizures, and coma. Severe hypoglycaemia is defined as any low blood glucose level leading to cognitive impairment requiring assistance from another person for recovery.

Assess the patient’s awareness of hypoglycaemia at each annual review.[37] In adults, use the Gold score or Clarke score.[37] 

Episodes of hypoglycaemia occur with different frequency among patients. Patients should check a 3 a.m. blood glucose if there is concern about risk of nocturnal hypoglycaemia. To manage nocturnal hypoglycaemia (symptomatic or detected on monitoring), review the patient’s knowledge and self-management skills, current insulin regimen, evening eating habits and previous physical activity.[37] Opt for an insulin type and regimen that is less likely to induce low glucose levels at night.[37] A bedtime snack is not always an effective way of decreasing the risk of nocturnal hypoglycaemia.[83] However, a bedtime snack without insulin (or overnight basal insulin reduced by 20%) is recommended if the patient exercises in the afternoon or evening.[57] Bedtime snacks might also be a suitable approach for patients in hospital.

Alcohol may cause acute hypoglycaemia, but both alcohol and exercise can cause delayed hypoglycaemia (by up to 24 hours).

Work with the patient to determine contributing factors, and the ability of the patient to recognise and treat hypoglycaemia appropriately. Advise patients (or parents/carers) that it is important to always have immediate access to a source of fast-acting glucose and blood glucose monitoring equipment so that they can respond quickly to symptoms or signs of hypoglycaemia.[35][37] Train and equip the patient’s family, friends, and/or carers (as appropriate) to give intramuscular glucagon for severe hypoglycaemia in an emergency.[35][37] 

Immediately treat mild to moderate hypoglycaemia in children and young people with oral fast-acting glucose, e.g., 10-20 g (liquid carbohydrate may be easier to swallow than solid). Fast-acting glucose may need to be given in frequent small amounts, because hypoglycaemia can cause vomiting.[35] Recheck the patient’s blood glucose levels within 15 minutes (fast-acting glucose should raise blood glucose levels within 5-15 minutes), and give more fast-acting glucose if they still have hypoglycaemia.[35] As the patient’s symptoms improve or their blood glucose levels return to normal, give oral complex long-acting carbohydrate to maintain blood glucose levels, unless the child or young person is about to have a snack or meal or having a continuous subcutaneous insulin infusion.[35]

For children and young people with type 1 diabetes who are in hospital, treat severe hypoglycaemia with 10% intravenous glucose if rapid intravenous access is possible. For children and young people with type 1 diabetes who are not in hospital, or if rapid intravenous access is not possible, treat severe hypoglycaemia with intramuscular glucagon or a concentrated oral glucose solution.[35] Do not use oral glucose solution if they have reduced consciousness, because this could be dangerous.[35] Seek senior assistance if the patient’s blood glucose levels do not respond or symptoms continue for more than 10 minutes.[35] As symptoms improve or blood glucose levels return to normal, and once the child or young person is sufficiently awake, give oral complex long-acting carbohydrate to maintain normal blood glucose levels. Check blood glucose repeatedly in children and young people who have persistently reduced consciousness after a severe hypoglycaemic episode, to determine whether further glucose is needed.[35]

If the patient is an adult and able to ingest orally, hypoglycaemia can be treated with a fast acting form of glucose.[37] If oral intake is not possible owing to a decreased level of consciousness, glucagon is required.[37] This can be administered intramuscularly (by a family member or friend who has been shown how to do this) or intravenously (by a healthcare professional adept at obtaining intravenous access).[37] The patient should be monitored for response at 10 minutes, and then given intravenous glucose if their level of consciousness is not improving significantly. Once it is safe for the patient to have it, they can be given oral carbohydrate. The patient will need continued observation by someone who has been warned of the risk of relapse.[37]

If hypoglycaemia becomes unusually problematic or frequent, review the possible causes including: inappropriate insulin regimens (incorrect dose distributions and insulin types); meal and activity patterns, including alcohol; injection technique and skills, including insulin resuspension if necessary; injection site problems; possible organic causes including gastroparesis; changes in insulin sensitivity (including drugs affecting the renin–angiotensin system and renal failure); psychological problems; previous physical activity; lack of appropriate knowledge and skills for self-management.[37] Consider referring children and young people with type 1 diabetes for assessment of cognitive function if they have frequent hypoglycaemia or recurrent seizures.

retinopathy

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Retinopathy is the most common microvascular complication of diabetes and its risk is increased at all levels of glycosylated haemoglobin (HbA1c) above the non-diabetic range. The incidence is 1 in 100 person-years for a mean HbA1c value of 37 mmol/mol (5.5%) and 9.5 in 100 person-years for a mean HbA1c value of 91 mmol/mol (10.5%).[127] There is an increased risk of retinopathy in women with pre-existing type 1 diabetes during pregnancy.[46]

Twenty years after diagnosis, most patients have evidence of retinopathy. Patients develop microaneurysms, exudates, haemorrhages, angiogenesis, and glaucoma.

Retinopathy is usually asymptomatic until its late stages, so screening is essential.

Primary prevention includes strict glycaemic control. Progression of very mild to moderate non-proliferative retinopathy can be delayed through glycaemic, blood pressure, and lipid control.[46] In advanced disease, photo-coagulation and vitrectomy can be done to prevent blindness. Intravitreal injections of antivascular endothelial growth factors are given for centre-involved macular oedema.[46]

diabetic kidney disease

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Diabetic kidney disease is the most common cause of end-stage renal disease (ESRD) in developed countries. In patients with type 1 diabetes, the annual incidence of microalbuminuria and albuminuria is between 1.3% and 3.8%.[135] In one cohort study, the cumulative risk of ESRD was 2.2% after 20 years and 7.0% after 30 years from the diabetes diagnosis.[136] 

The pathogenesis of diabetic nephropathy involves glomerular mesangial sclerosis leading to proteinuria and progressive decline in glomerular filtration. Increased urinary albumin excretion (>30 mg/day) is the earliest sign of disease and a marker of much increased cardiovascular risk. Test yearly in people who have had type 1 diabetes for 5 years or more.[46]

Glycaemic control and blood pressure control with an ACE inhibitor or angiotensin-II receptor blocker delays onset and slows progression of disease.[37][137][138] In the UK, the National Institute for Health and Care Excellence (NICE) recommends starting angiotensin-converting enzyme (ACE) inhibitors and, with the usual precautions, titrating to full dose in all adults with type 1 diabetes who have confirmed nephropathy with ACR ≥3 mg/mmol. If ACE inhibitors are not tolerated, NICE recommends substituting angiotensin 2 receptor antagonists. NICE does not recommend combination therapy.[37]

peripheral or autonomic neuropathy

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More than 50% of patients will develop neuropathy.[139]

Strict glycaemic control prevents onset and delays progression of diabetic neuropathy, which manifests most commonly as distal symmetric polyneuropathy affecting sensory axons.

The duration and extent of hyperglycaemia are the greatest risk factors, although other cardiovascular risk factors probably also contribute.

The other most common types of neuropathy include mononeuropathy, mononeuritis multiplex, polyradiculopathies, and autonomic neuropathy.

Once distal symmetric polyneuropathy is diagnosed, simple inspection should be performed at 3- to 6-month intervals, and referral for podiatric care and special footwear should be made. There are several medications that are particularly effective and may be considered. In the US, Food and Drug Administration-approved medications for diabetic neuropathic pain include pregabalin, duloxetine, and tapentadol. Other treatments that are not approved everywhere for this indication may also be helpful, including tricyclic antidepressants, anticonvulsants, a 5-hydroxytryptamine and noradrenaline (norepinephrine) uptake inhibitor, or capsaicin cream.[46]

For autonomic neuropathy, current treatments for this complication are mostly inadequate. However, symptom management can be considered: for example, compressive stockings for postural hypotension.[46]

cardiovascular disease

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Cardiovascular disease is the major cause of death and a major cause of morbidity for patients with diabetes.

Intensive glycaemic control has been shown to decrease the incidence of macrovascular disease in type 1 diabetes.[130] During the 30-year follow-up of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, high doses of insulin were associated with a less favourable cardiometabolic risk profile (higher body mass index, pulse rate, triglycerides, lower high-density lipoprotein [HDL] cholesterol), but intensive control continued to have long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes.[131][140]

The cardiovascular disease risk can be further decreased by modification of other cardiovascular risk factors.[141] Lifestyle and behavioural therapy are essential components of treatment.

Hypertension is often secondary to underlying nephropathy in patients with type 1 diabetes. Blood pressure should be treated with an ACE inhibitor or angiotensin-II receptor blocker if >135/85 mmHg (>130/80 if the patient has albuminuria or two or more features of metabolic syndrome).[37] Most patients will require two or three drugs to reach their goal. Intensifying antihypertensive therapy to blood pressure targets <140/90 was associated with a lower risk of coronary artery disease in one study.[142]

For patients of all ages with diabetes and overt cardiovascular disease, high-intensity statin therapy should be added to lifestyle therapy. For patients of all ages with diabetes and overt cardiovascular disease, high-intensity statin therapy should be added to lifestyle therapy. For adults with type 1 diabetes without known cardiovascular disease, consider statin treatment for the primary prevention of cardiovascular disease. Specifically, offer statin treatment to those who are older than 40 years, or have had diabetes for more than 10 years, or have established nephropathy, or have other CVD risk factors.[143] Intensive lifestyle therapy and optimal glycaemic control are recommended to decrease cardiovascular risk in patients with triglycerides ≥1.7 mmol/L (≥150 mg/dL) and/or HDL <1 mmol/L (<40 mg/dL) (HDL <1.3 mmol/L [<50 mg/dL] in women).[46] There is no specific low-density lipoprotein (LDL) target.

Children should have a fasting lipid profile once adequate glucose control is achieved if age ≥2 years, with subsequent testing performed at age 9-11 years.[46] Monitoring can be every 3 years if LDL <2.6 mmol/L (<100 mg/dL).[46] The optimal pharmacological treatment of hyperlipidaemia in children has not been clearly defined, although an initial approach to lipid lowering should include modifications to diet and increased exercise. Statins are not approved for children aged <10 years.[46]

All adult patients with diabetes and cardiovascular disease should be treated with aspirin for secondary prevention (75-162 mg/day). Do not offer aspirin for primary prevention in adults with type 1 diabetes.[37] All patients should have smoking-cessation counselling and treatment as needed.

Patients aged >55 years, with or without hypertension, but with cardiovascular disease, dyslipidaemia, increased urinary albumin excretion, or smoking may benefit from an ACE inhibitor to reduce the risk of cardiovascular events.[144]

No evidence-based guidelines exist for screening asymptomatic patients for coronary heart disease.[46]

depression

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As a chronic disease, type 1 diabetes may impact on the psychological and psychosocial wellbeing of the patient. Manifestations of this may include diabetes 'burnout' and depression. Adults with type 1 diabetes are at three times the risk of clinical depression compared with those without type 1 diabetes.[145] The prevalence of depression in diabetes is higher in women (28%) compared with men (18%).[146] The risk of psychological adjustment and psychiatric disorders may also be higher in adolescents, at diagnosis, or when there is a change in disease status.[147][148][149] Consider seeking the support of a psychologist, preferably within a specialist type 1 diabetes service, if you are concerned.

eating disorders

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Be alert to the possibility of bulimia nervosa, anorexia nervosa and disordered eating in patients with type 1 diabetes with over-concern with body shape and weight, low BMI, hypoglycaemia, or sub-optimal overall blood glucose control. Consider an early (or if needed, urgent) referral to local eating disorder services for patients with type 1 diabetes who have an eating disorder.[37]

Specifically consider whether an eating disorder, and associated concerns about body size and weight, might be influencing how the patient uses their insulin.[37]

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