Complications

Complications table
ComplicationTimeframeLikelihood

diabetic ketoacidosis (DKA)

short termhigh

DKA is the classical acute complication of type 1 diabetes, characterised by hyperglycaemia and metabolic acidosis.

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, shortness of breath, abdominal pain, nausea, vomiting, and altered sensorium.

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 1- to 4-hourly monitoring of electrolytes is required. Insulin infusion must continue until ketosis has resolved and a subcutaneous injection of insulin has been given.

Closure of the anion gap will indicate correction of the ketoacidosis.

Potassium repletion is usually indicated because initially apparently normal serum potassium does not reflect true total body depletion.

Treatment with bicarbonate is not indicated except when arterial blood pH is <6.9. Serum phosphorus level is usually low, but does not require replacement unless it is < 1.0 mg/dL (0.323 mmol/L).[125]

hypoglycaemia

short termhigh

The main complication of insulin treatment is hypoglycaemia. The American Diabetes Association defines level 1 hypoglycaemia as ≥3.0 mmol/L but <3.9 mmol/L (≥54 mg/dL but <70 mg/dL), requiring treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Level 2 hypoglycaemia (clinically significant) is defined as <3.0 mmol/L (<54 mg/dL). Level 3 hypoglycaemia (severe) is defined as any low blood glucose level leading to cognitive impairment requiring assistance from another person for recovery.[1]

Patients with type 1 diabetes are generally sensitive to insulin.

Therefore, even a slightly higher dose of insulin, decreased food intake, or increased physical activity can lead to hypoglycaemia. Children <6-7 years old may not be aware of hypoglycaemia, necessitating less stringent goals for glucose control.[1] Other risk factors for hypoglycaemia include a prior episode of hypoglycaemia, hypoglycaemic unawareness, autonomic neuropathy, and long duration of diabetes. Alcohol and exercise can cause delayed hypoglycaemia, up to 24 hours after the event.

If the patient is able to ingest orally, hypoglycaemia can be treated with 118 mL (4 fluid ounces) of fruit juice or sweetened fluids or glucose tablets (15-20 g of carbohydrate).[1] Blood sugar should be tested and treatment effect apparent in 15 minutes.

If oral intake is not possible, glucagon (parenteral or intranasal administration) or intravenous dextrose is required.

Patient carers and family members of patients with type 1 diabetes should be educated about the signs and symptoms of hypoglycaemia and taught how to administer oral glucose or glucagon intranasally or as an intramuscular or subcutaneous injection. Unless hypoglycaemia is recurring, the next meal or snack should be eaten and the next dose of basal insulin should be given.

Episodes of hypoglycaemia and the possibility of hypoglycaemia unawareness should be assessed at each visit. A strict period of several weeks without hypoglycaemia may improve hypoglycaemic awareness in some patients.

retinopathy

long termhigh

Retinopathy is the most common microvascular complication of diabetes and its risk is increased at all levels of glycosylated hemoglobin (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%).[118] There is an increased risk of retinopathy in women with pre-existing type 1 diabetes during pregnancy.[1]

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.[1] In advanced disease, photo-coagulation and vitrectomy can be done to prevent blindness.[1] Intravitreal injections of antivascular endothelial growth factors are given for centre-involved macular oedema.[1]

diabetic kidney disease

long termhigh

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%.[126] 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.[127] 

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.[1]

Glycaemic control and blood pressure control with an ACE inhibitor or angiotensin-II receptor blocker delays onset and slows progression of disease.[128][129]

peripheral or autonomic neuropathy

long termhigh

More than 50% of patients will develop neuropathy.[130]

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.[1]

For autonomic neuropathy, current treatments for this complication are mostly inadequate. However, symptom management can be considered: for example, compressive stockings for postural hypotension.[1]

cardiovascular disease

long termhigh

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.[121] 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.[122][131]

The cardiovascular disease risk can be further decreased by modification of other cardiovascular risk factors.[132] 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 to <140/80 mm Hg with an ACE inhibitor or angiotensin-II receptor blocker; most patients will require two or three drugs to reach goal. Intensifying antihypertensive therapy to blood pressure targets <140/90 was associated with a lower risk of coronary artery disease in one study.[133]

For patients of all ages with diabetes and overt cardiovascular disease, high-intensity statin therapy should be added to lifestyle therapy. For patients without known cardiovascular disease, individualisation of statin therapy according to their cardiovascular disease risk score is recommended.[134] ASCVD risk estimator external link opens in a new window

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) (<1.3 mmol/L [<50 mg/dL] among women).[1] 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.[1] Monitoring can be every 3 years if LDL <2.6 mmol/L (<100 mg/dL).[1] 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.[1]

All adult patients with diabetes and cardiovascular disease should be treated with aspirin for secondary prevention (75-162 mg/day). Aspirin can be considered for primary prevention for men and women at increased cardiovascular risk, after a comprehensive discussion with the patient on the benefits versus the comparable increased risk of bleeding.[1] 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.[135]

No evidence-based guidelines exist for screening asymptomatic patients for coronary heart disease.[1]

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