Complications

Complications table
ComplicationTimeframeLikelihood

diabetic kidney disease

long termlow

Chronic kidney disease occurs in about 40% of patients with type 2 diabetes over time. Prevalence of end-stage renal disease is about 1% in those with type 2 diabetes (cross-sectional data).[172] Chronic kidney disease is driven by uncontrolled blood pressure and glucose, and increases the risk of cardiovascular disease at least fourfold. An estimated glomerular filtration rate (eGFR) <60 mL/1.73m²/minute establishes a diagnosis of chronic kidney disease, and microalbuminuria or albuminuria establishes a diagnosis of nephropathy. Either of these findings should prompt increased efforts to aggressively manage systolic blood pressure, avoid non-steroidal anti-inflammatory drugs (NSAIDs), and consider use of antihyperglycaemic drugs with low risk of hypoglycaemia and pronounced renal benefits (such as sodium-glucose co-transporter 2 [SGLT2] inhibitors or glucagon-like peptide-1 [GLP-1] agonists).[106][127]

Also important are use of an ACE inhibitor or angiotensin-II receptor antagonist, and optimisation of glucose control. When eGFR is lower than 30 mL/minute/1.73m², referral to a nephrologist for expectant management of end-stage renal disease is necessary.

Renal failure predisposes patients to anaemia and hypoglycaemia; in renal failure, insulin doses may need to be reduced.

impaired vision

long termlow

In the US, approximately 25% of patients with type 2 diabetes have retinopathy at diagnosis, presumably as a consequence of unrecognised disease.[182] In a global study, prevalence of diabetic retinopathy in newly diagnosed type 2 diabetes varied from 1.5% to 31%, with higher prevalence observed in developing countries.[183] Risk of vision loss is increased by poor blood pressure and glucose control, and by failure to regularly screen for retinopathy, macular degeneration, glaucoma, and cataracts.[184][185] The risk of all of these eye conditions is increased in diabetes.

lower extremity amputation

long termlow

Incidence of lower extremity amputation (LEA) is between 2.5 and 4 per 1000 people with diabetes per year, with significant geographic variation in LEA rates within countries.[186] Incidence rates of major LEA, defined as loss of lower limb through or above the ankle, are declining in patients with diabetes; however, there is some evidence that minor LEA (loss of lower limb below the level of the ankle) incidence rates are increasing, with about half being toe or metatarsal amputations.[170]

Risk is aggravated by neuropathy and by peripheral vascular disease, and can be reduced by smoking cessation; aggressive management of glucose, blood pressure, and lipids; use of customised footwear in patients with known neuropathy or foot deformity; and prompt and aggressive management of lower extremity infections.

cardiovascular disease

variablehigh

Cardiovascular disease (CVD) and CVD-associated mortality is declining in patients with diabetes, particularly in high-income countries.[170] Adults with type 2 diabetes are twice as likely to die of stroke or myocardial infarction compared with those without diabetes, and they are more than 40 times more likely to die of macrovascular than to die of microvascular complications of diabetes.[65][66] To reduce cardiovascular risk, blood pressure, lipids, and tobacco use should be adequately managed. Use of statins, ACE inhibitors, metformin, aspirin, empagliflozin, liraglutide, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors may reduce cardiovascular mortality or all-cause mortality in selected patients with type 2 diabetes. In the ACCORD and ADVANCE randomized trials, near-normal glucose control failed to decrease cardiovascular mortality or all-cause mortality in type 2 diabetes, and in one of those studies, increased all-cause mortality. However, ACCORD and ADVANCE trials did not use empagliflozin, liraglutide, or PCSK9 inhibitors. Many studies suggest that HbA1c ≥64 mmol/mol (≥8%) increases risk of major cardiovascular events.[97][98]

Increased fatigability may be an early warning sign of progressive cardiovascular disease; clinicians should have a low threshold for cardiac evaluation of any symptoms that are potentially cardiac-related in patients with type 2 diabetes.

congestive heart failure (CHF)

variablehigh

Diabetes is a risk factor for CHF, with poor glycaemic control associated with greater risk for the development of CHF and worsening of clinical outcomes for patients with CHF and diabetes.[174] CHF occurs in up to 10% to 15% of patients with diabetes.[175] CHF in type 2 diabetes is often related to uncontrolled hypertension, or ischaemic coronary disease, but may also occur as a microvascular complication of diabetes.

Requires management with ACE inhibitor/angiotensin-II receptor antagonist, diuretics, and other medications.

Must rule out underlying causes such as myocardial infarction, atrial fibrillation, thyroid disorders, anaemia, or structural heart disease.

stroke

variablehigh

Related to uncontrolled blood pressure, glucose, and lipids. Lifetime risk is higher in women than in men with diabetes.[176]

Prompt hospitalisation and neurological evaluation, with possible emergency use of tissue plasminogen activator (TPA) or other therapeutic strategies, may minimise damage and maximise potential for recovery of function.

infection

variablemedium

Hyperglycaemia compromises defence against bacterial infections by several mechanisms including impaired phagocytosis.

Normalisation of blood glucose reduces the risk of infections, especially cystitis, cellulitis, and pneumonia. Immunisation reduces the risk of serious pneumococcal, Haemophilus influenzae, and influenza infections.

Aggressive infection-specific therapy and supportive therapy including adequate glucose control are key to successful treatment.

periodontal disease

variablemedium

Type 2 diabetes is associated with periodontal disease, but causality is not established.[177] In one large epidemiological survey, periodontal disease was an independent predictor of incident diabetes.[177] Bidirectional risk has been postulated.[178]

Control of periodontal disease and hyperglycaemia are mutually beneficial. Routine preventative dental care is important for people with type 2 diabetes.[177]

treatment-related hypoglycaemia

variablemedium

Related to treatment with insulin and/or insulin secretagogues (sulfonylureas or meglitinides), alone or in combination with other drugs. [ Cochrane Clinical Answers logo ] A glucose alert value is defined as ≤3.9 mmol/L (≤70 mg/dL), requiring treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Clinically significant hypoglycaemia is defined as <3.0 mmol/L (<54 mg/dL), indicating serious, clinically important hypoglycaemia.[2] Low blood sugars are common in patients who are trying to achieve HbA1c <53 mmol/mol (<7%). Hypoglycaemia is usually associated with warning signs, such as rapid heartbeat, perspiration, shakiness, anxiety, confusion, and hunger. Hypoglycaemia unawareness (absence of symptoms during hypoglycaemia) and severe hypoglycaemia, defined as a blood sugar so low that assistance from another person or medical personnel is required to treat it, occurs in 1% to 3% of type 2 diabetes patients per year. Older people and those with comorbid heart disease, congestive heart failure, chronic kidney disease, or depression are at substantially increased risk for severe hypoglycaemia.[179]

Patients should be counselled on recognition, prevention, and treatment of hypoglycaemia and should carry with them glucose tablets or comparable 20 g fast-acting carbohydrate product. Patients using alpha-glucosidase inhibitors must use glucose tablets for hypoglycaemia because absorption of conventional carbohydrates is slowed by the medication.

depression

variablemedium

When glycaemic goals or adherence to treatment plan are difficult to achieve, the presence of depression should be considered. Screening with a validated tool such as the Patient Health Questionnaire (PHQ)-9 may help with identification and diagnosis. The cross-sectional prevalence of depression is 10% to 25% in people with diabetes.[189] Adults with type 2 diabetes diagnosed before age 40 years have excess hospitalisations across their lifespan, which includes a large burden of mental illness in young adulthood.[190]

obstructive sleep apnoea

variablemedium

Obstructive sleep apnoea is common among overweight and obese adults, and has been associated with insulin resistance and altered glucose metabolism. Further studies are needed to assess the effect of continuous positive airway pressure (CPAP) on glycaemic control, as results have varied.[191][192][193]

The American Diabetes Association recommends assessment of sleep pattern and duration as part of a comprehensive approach to lifestyle and glycaemic control.[2]

diabetic ketoacidosis

variablelow

Commonly thought of in type 1 diabetes; however, can occur in type 2 diabetes and an unusual type of diabetes known as ketosis-prone diabetes. Infection and poor diabetic medication adherence are the most common reasons for developing diabetic ketoacidosis, but no precipitating factors may be apparent.[180]

Criteria of diabetic ketoacidosis is the same, regardless of type of diabetes and is potentially fatal if not properly treated.

Hydration, parenteral insulin therapy, intensive monitoring, and careful management of electrolyte imbalances and acidosis are important for successful therapy.

non-ketotic hyperosmolar state

variablelow

Occurs most commonly in older people with type 2 diabetes and usually evolves insidiously over days to weeks.[181] Characterised by severe hyperglycaemia, hyperosmolality, and volume depletion, in the absence of severe ketoacidosis.

Hydration, insulin therapy, and careful clinical and laboratory monitoring are the basis of successful therapy.

autonomic or peripheral neuropathy

variablelow

Diabetic peripheral neuropathy is the most common chronic complication of diabetes, characterised by the presence of peripheral nerve dysfunction, diagnosed after the exclusion of other causes.[187] Pain is the outstanding complaint in most patients, but many patients are completely asymptomatic.

Manifestations of autonomic neuropathy may include: erectile dysfunction, diarrhoea, gastroparesis, or orthostatic hypotension.

For type 2 diabetes the effects of glycaemic control on peripheral or autonomic neuropathy are less clear than for type 1 diabetes, with early data suggesting that glucose control is beneficial if started earlier in the disease course, but later studies not confirming these findings.[188]

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