diabetic ketoacidosis (DKA)
DKA is the classical acute complication of type 1 diabetes, characterized by hyperglycemia and metabolic acidosis.
The most common precipitants are missed insulin injections or physiologic stresses such as infection or myocardial infarction.
Workup (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.
Hyperglycemia 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).
The main complication of insulin treatment is hypoglycemia. The American Diabetes Association defines level 1 hypoglycemia as ≥54 mg/dL but <70 mg/dL (≥3.0 mmol/L but <3.9 mmol/L), requiring treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy. Level 2 hypoglycemia (clinically significant) is defined as <54 mg/dL (<3.0 mmol/L). Level 3 hypoglycemia (severe) is defined as any low blood glucose level leading to cognitive impairment requiring assistance from another person for recovery.
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 hypoglycemia. Children <6 years old may not be aware of hypoglycemia, necessitating less stringent goals for glucose control. Other risk factors for hypoglycemia include a prior episode of hypoglycemia, hypoglycemic unawareness, autonomic neuropathy, and long duration of diabetes. Alcohol and exercise can cause delayed hypoglycemia, up to 24 hours after the event.
If the patient is able to ingest orally, hypoglycemia can be treated with ingestion of glucose (15-20 g) or carbohydrate-containing food. 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 caregivers and family members of patients with type 1 diabetes should be educated about the signs and symptoms of hypoglycemia and taught how to administer oral glucose or glucagon intranasally or as an intramuscular or subcutaneous injection . Unless hypoglycemia is recurring, the next meal or snack should be eaten and the next dose of basal insulin should be given.
Episodes of hypoglycemia and the possibility of hypoglycemia unawareness should be assessed at each visit. A strict period of several weeks without hypoglycemia may improve hypoglycemic awareness in some patients.
Retinopathy is the most common microvascular complication of diabetes and its risk is increased at all levels of glycosylated hemoglobin (HbA1c) above the nondiabetic range. The incidence is 1 in 100 person-years for a mean HbA1c value of 5.5% and 9.5 in 100 person-years for a mean HbA1c value of 10.5%. There is an increased risk of retinopathy in women with pre-existing type 1 diabetes during pregnancy.
Twenty years after diagnosis, most patients have evidence of retinopathy. Patients develop microaneurysms, exudates, hemorrhages, angiogenesis, and glaucoma.
Retinopathy is usually asymptomatic until its late stages, so screening is essential.
Primary prevention includes strict glycemic control. Progression of very mild to moderate nonproliferative retinopathy can be delayed through glycemic, blood pressure, and lipid control. In advanced disease, photocoagulation and vitrectomy can be done to prevent blindness. Intravitreal injections of antivascular endothelial growth factors are given for center-involved macular edema.
diabetic kidney disease
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%. 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.
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.
peripheral or autonomic neuropathy
More than 50% of patients will develop neuropathy.
Strict glycemic 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 hyperglycemia 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 for this indication may also be helpful, including tricyclic antidepressants, anticonvulsants, a 5-hydroxytryptamine and norepinephrine uptake inhibitor, or capsaicin cream.
For autonomic neuropathy, current treatments for this complication are mostly inadequate. However, symptom management can be considered: for example, compressive stockings for postural hypotension.
Cardiovascular disease is the major cause of death and a major cause of morbidity for patients with diabetes.
Intensive glycemic control has been shown to decrease the incidence of macrovascular disease in type 1 diabetes. 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 favorable 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.
The cardiovascular disease risk can be further decreased by modification of other cardiovascular risk factors. Lifestyle and behavioral 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.
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, individualization of statin therapy according to their cardiovascular disease risk score is recommended. ASCVD risk estimator external link opens in a new window
Intensive lifestyle therapy and optimal glycemic control are recommended to decrease cardiovascular risk in patients with triglycerides ≥150 mg/dL (≥1.7 mmol/L) and/or HDL <40 mg/dL (<1 mmol/L) (<50 mg/dL [<1.3 mmol/L] among women). 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. Monitoring can be every 3 years if LDL <100 mg/dL (<2.6 mmol/L). The optimal pharmacologic treatment of hyperlipidemia 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.
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. All patients should have smoking-cessation counseling and treatment as needed.
Patients aged >55 years, with or without hypertension, but with cardiovascular disease, dyslipidemia, increased urinary albumin excretion, or smoking may benefit from an ACE inhibitor to reduce the risk of cardiovascular events.
No evidence-based guidelines exist for screening asymptomatic patients for coronary heart disease.
Adults with type 1 diabetes are at three times the risk of clinical depression compared with those without type 1 diabetes. The prevalence of depression in diabetes is higher in women (28%) compared with men (18%). 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.
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