Complications
Diabetic ketoacidosis (DKA) is the classic acute complication of type 1 diabetes, characterized by hyperglycemia and metabolic acidosis. In the setting of insulin deficiency, stress hormones including glucagon, cortisol, and catecholamines raise blood glucose levels and stimulate ketogenesis.[46] Hyperglycemia and ketosis cause osmotic diuresis leading to dehydration.[46]
The most common precipitants of DKA are missed insulin injections or physiologic stressors such as infection or myocardial infarction.[46]
Workup (e.g., ECG, search for infection) is indicated to detect precipitating factors.[46]
Symptoms tend to be due to dehydration and metabolic acidosis and include dry mouth, Kussmaul breathing (which consists of deep breaths with a fruity odor due to the presence of acetone, a breakdown product of the ketone acetoacetic acid), abdominal pain, nausea, vomiting, and altered sensorium.[46]
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. One- to two-hourly monitoring of blood glucose and 4-hourly monitoring of electrolytes, phosphate, creatinine, blood ketones (beta-hydroxybutyrate), and venous pH is required.[46] Insulin infusion must continue until ketosis has resolved and a subcutaneous injection of insulin has been given. Subcutaneous insulin alone has been used successfully to manage mild cases of DKA.[46]
Ongoing patient education and the integration of diabetes technology, such as continuous glucose monitoring and insulin pump therapy, have been shown to significantly reduce the incidence of DKA.[236]
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); level 2 hypoglycemia (clinically significant) as <54 mg/dL (<3.0 mmol/L); and level 3 hypoglycemia (severe) as any low blood glucose level leading to cognitive and/or physical impairment requiring assistance from another person for recovery.[1]
Patients with type 1 diabetes are generally sensitive to insulin.[1] Therefore, even a slightly higher dose of insulin, decreased food intake, or increased physical activity can lead to hypoglycemia.[1] Young children and older people are especially vulnerable to hypoglycemia as they are less able to recognize the symptoms and clearly communicate their needs (and older adults are more likely to have comorbidities such as chronic kidney disease (CKD) and cognitive impairment which further increase the risk), potentially necessitating less stringent goals for glucose control.[1] Other clinical risk factors for hypoglycemia include a prior episode of hypoglycemia (especially level 2 or 3 events; this is the strongest risk factor for hypoglycemia recurrence and severity), hypoglycemic unawareness (due to impaired hormonal counterregulation which often occurs in those with recurrent hypoglycemia), autonomic neuropathy, and long duration of diabetes.[1] Alcohol and exercise can cause delayed hypoglycemia, up to 24 hours after the event.[1][48] Socioeconomic and cultural factors may be relevant also, including religious fasting and food insecurity.[1] Hypoglycemia risk should be considered when choosing treatment plans and glycemic goals.[1]
Hypoglycemia should be asked about at every visit and all people with type 1 diabetes should be screened for possible hypoglycemia unawareness at least yearly.[1]
Type 1 diabetes may be associated with autoimmune skin diseases such as necrobiosis lipoidica, granuloma annulare, vitiligo, and bullosis diabeticorum. In addition, there is a small risk of insulin-induced lipodystrophy (a cause of erratic insulin absorption that can lead to increased glycemic variability and unexplained hypoglycemia), allergic or irritant contact dermatitis caused by insulin pumps or CGM sensors or adhesives, and infection at site of insertion.[1][48] Skin exam should form a routine part of diabetes care, and any skin reactions addressed promptly to avoid interference with use of diabetes devices.[1][48] Lipodystrophy can be avoided by rotating injection or pump insertion sites.[1] One study found that a basic proactive skin-care program (including use of emollient, gentle insertion and removal of devices, and avoidance of disinfection of the skin) could help to prevent some diabetes device-induced skin reactions.[270]
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%.[226] There is an increased risk of development or progression of diabetic retinopathy in individuals with preexisting type 1 diabetes during pregnancy.[1]
Most patients have evidence of retinopathy 20 years after diagnosis of diabetes. Patients develop microaneurysms, exudates, hemorrhages, angiogenesis, and glaucoma.
Retinopathy may be asymptomatic at any stage, even advanced, so screening is essential to ensure prompt diagnosis and intervention that can prevent vision loss.[1] Early referral to an ophthalmologist is recommended if there is any level of diabetic macular edema, moderate or worse nonproliferative, or any proliferative, diabetic retinopathy.[1]
Primary prevention includes strict glycemic control. Progression of very mild to moderate nonproliferative retinopathy can be delayed through glycemic, blood pressure, and lipid control (and prevention of development or progression of kidney disease).[1] It should be noted that rapid reduction of HbA1c (e.g., in the context of preconception) can be associated with worsening retinopathy.[1] In advanced disease, panretinal laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs can be administered to reduce risk of blindness.[1] Intravitreal injections of anti-VEGF drugs are first-line treatment for center-involved macular edema with impaired vision acuity.[1]
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%.[237] Typically, diabetic nephropathy develops after 10 years of type 1 diabetes.[1] In one cohort study, the cumulative risk of ESRD was 2.2% after 20 years and 7.0% after 30 years from diabetes diagnosis.[238]
The pathogenesis of diabetic nephropathy involves glomerular mesangial sclerosis leading to proteinuria and progressive decline in glomerular filtration. It is driven by uncontrolled blood pressure and glucose, and increases the risk of cardiovascular disease at least fourfold. It is usually a clinical diagnosis made based on the presence of albuminuria and/or reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² in the absence of signs or symptoms of other primary causes of kidney damage.[1] Either of these findings should prompt increased efforts to aggressively manage blood pressure (using an ACE inhibitor or angiotensin-II receptor antagonist first-line) and lipids, optimize glucose control, and modify lifestyle factors (physical activity, smoking, and nutrition).[1][239][240]
Testing of urinary albumin and estimated glomerular filtration rate (eGFR) should be done yearly in adults who have had type 1 diabetes for 5 years or more, and may need to be repeated more frequently if they have chronic kidney disease (CKD).[1] In children, annual screening for albuminuria should be considered at puberty or at age ≥10 years, whichever is earlier, once the patient has had diabetes for 5 years.[1]
Patients should be referred to a nephrologist if they have continuously worsening renal function tests, eGFR <30 mL/min/1.73 m², or rapidly progressing kidney disease, or if there is uncertainty about etiology.[1] Renal failure predisposes patients to anemia and hypoglycemia; insulin doses may therefore need to be reduced.[1]
Increasing duration and extent of hyperglycemia, as well as greater glycemic variability, are the strongest risk factors for neuropathy, although other cardiovascular risk factors probably also contribute.[241] Optimizing glucose management is recommended to prevent or delay the development of neuropathy, and treatment of other modifiable risk factors (e.g., lipids and blood pressure) may reduce disease progression in type 1 diabetes.[1]
Diabetic neuropathy refers to a group of disorders with varying presentations: peripheral neuropathy and autonomic neuropathy are two key groups.[1] It is a diagnosis of exclusion and other causes of neuropathy should be considered and investigated accordingly.[1] The most common early symptoms of diabetic peripheral neuropathy (DPN) are pain and dysesthesia, but up to 50% of DPN may be asymptomatic.[1] Annual screening (from 5 years after diagnosis) is therefore important, as missed diagnosis may result in diabetic foot ulcers and amputations.[1] Manifestations of autonomic neuropathy may include erectile dysfunction, diarrhea, gastroparesis, or orthostatic hypotension. Screening is recommended at least annually (from 5 years after diagnosis).[1]
Cardiovascular disease (CVD) is the major cause of death and a major cause of morbidity for patients with diabetes. It is the leading cause of hospital admission among patients with diabetes, with ischemic/coronary heart disease as the predominant subtype.[242]
Intensive glycemic control has been shown to decrease the incidence of macrovascular disease in type 1 diabetes.[229] 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 CVD in type 1 diabetes.[230][243]
CVD risk can be further decreased by modification of other cardiovascular risk factors (e.g., hypertension, dyslipidemia, and smoking), which should be assessed at least once a year in adult patients.[1][244] Use of statins, ACE inhibitors/angiotensin-II receptor antagonists, aspirin, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, ezetimibe, and bempedoic acid may reduce mortality.[1] Lifestyle and behavioral therapy are also essential components of treatment.[1]
In children, blood pressure should be checked at every visit.[1] Treatment of hypertension (defined as blood pressure consistently ≥95th percentile for age, sex, and height or, in adolescents ages ≥13 years, ≥130/80 mmHg) involves lifestyle modification and initiation of an ACE inhibitor or angiotensin-II receptor antagonist.[1] A fasting lipid profile should be checked soon after diagnosis once adequate glucose control is achieved if age ≥2 years, with subsequent testing performed at ages 9-11 years if results are within acceptable risk levels.[1] Monitoring can then be every 3 years if LDL <100 mg/dL (<2.6 mmol/L).[1] 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.[1] Statins are not approved for children age <10 years.
Up to 34% of people with diabetes will develop a diabetic foot ulcer, and at least half of these wounds will develop some form of infection, increasing the risk for hospitalization and amputation.[252] Foot ulceration and amputation are major causes of morbidity and mortality.[1] The cause can be multifactorial, including presence of diabetic peripheral neuropathy, peripheral arterial disease (PAD), and foot deformity.[1]
Prompt recognition of at-risk feet and preulcerative lesions is key to initiating treatment that can prevent adverse outcomes.[1] The American Diabetes Association (ADA) recommends that all adults with type 1 diabetes should have a comprehensive foot evaluation at least annually to identify risk factors, and evidence of sensory loss (or previous ulcers or amputations) should prompt foot inspection at every visit.[1] Evidence of PAD should be further investigated and may require referral for further vascular assessment.[1] In children, an annual comprehensive foot exam, along with an assessment of symptoms of neuropathic pain, should be initiated at the start of puberty or at age ≥10 years, whichever is earlier, once the child has had type 1 diabetes for 5 years.[1]
People with foot ulcers or high-risk feet (e.g., those on dialysis, those with Charcot foot, those with a history of prior ulcers or amputation, and those with PAD) should be cared for using an interprofessional approach facilitated by a podiatrist.[1]
All people with diabetes should be taught general foot care, including how to examine their feet and identify early foot problems.[1] Barriers to foot self-care (e.g., visual, cognitive or movement difficulties) should be addressed.[1] Initial treatment may include use of moisturizers for dry skin, nail-care recommendations and support, and use of pressure-relieving orthoses.[1] The use of specialized footwear is recommended for those at high-risk of ulceration (e.g., those with loss of protective sensation, deformity, ulcers, callous formation, poor circulation, or history of amputation).[1]
Youth with type 1 diabetes have a higher risk of developing disordered eating behavior, particularly insulin misuse/omission, bulimia nervosa, and binge eating disorder.[48][258] Disordered eating is twice as prevalent in people with type 1 diabetes than in those without diabetes.[259] The most commonly reported disordered eating behavior in people with type 1 diabetes is omission of insulin leading to glycosuria in order to lose weight. The repeated insulin omission can then lead to short-term complications such as dehydration, fatigue, and muscle breakdown, and long-term macrovascular complications.[260] The American Diabetes Association suggests screening for disordered or disrupted eating when patients present with signs and symptoms (e.g., unexplained weight loss, hyperglycemia, and diabetic ketoacidosis) and /or behavioral and emotional indicators (e.g., secrecy around eating and excessive concern about weight).[1] The International Society for Pediatric and Adolescent Diabetes (ISPAD) recommends screening for symptoms disordered eating in children age ≥12 years using validated tools at the initial visit, at periodic intervals, and when there is a change in disease, treatment, or life circumstance.[48] An interprofessional approach to management of disordered eating and disrupted eating patterns is recommended due to the complexity of their comorbidity with diabetes.[1]
Adults with type 1 diabetes are at three times the risk of clinical depression than those without type 1 diabetes.[253] The prevalence of depression in diabetes is higher in women (28%) compared with men (18%).[254] One systematic review and meta-analysis found that the prevalence of depression in children with type 1 diabetes was 22.2%. This prevalence was higher among girls (29.7%) than boys (19.7%) and was higher in lower-middle-income countries (29.3%).[255]
The risk of psychologic adjustment and psychiatric disorders may also be higher in adolescents, at diagnosis, or when there is a change in disease status.[48][256][257] Recurrent DKA should prompt consideration of mental health problems (as should insulin omission or overdose, and chronically very high HbA1c).[48] Mental health problems in people with type 1 diabetes may lead to early complications and mortality.[48]
Diabetes distress is distinct from depression (though the two share some features), and refers to negative psychologic reactions related to the emotional burdens of managing diabetes.[1] It is prevalent in people with diabetes (up to 45% in some studies), and can also affect family and caregivers.[1] Diabetes distress can significantly impact self-management and adherence, and is associated with higher HbA1c levels and reduced health-related quality of life.[1][48]
Anxiety symptoms and disorders are also common in those with diabetes, and can affect self-management.[1] Up to 30% of youth with type 1 diabetes have significant anxiety symptoms (which overlap significantly with diabetes distress).[48]
Mental health problems should be regularly screened for and promptly managed, with referral made to qualified behavioral health professionals or other appropriate specialist services if indicated, ideally one with diabetes experience.[1] Education and behavioral/psychologic interventions (e.g., motivational interviewing) have been shown to reduce diabetes distress.[1] Use of diabetes technology, such as continuous glucose monitors, may be helpful.[1]
Bone fragility is a complication of diabetes that can affect patients of different ages with different disease severity, as well as the duration and the presence of other complications.[249][264] People with type 1 diabetes have lower bone mineral density and are at a greater risk of fracture than individuals without diabetes (more than five times for hip fracture and two times for nonvertebral fractures).[265] One population-based cohort reported a 14% increase in the risk for all fracture types in childhood, and in adults with type 1 diabetes the risk was double that of healthy controls, impacting both sexes equally.[48] One systematic review and meta-analysis found that patients with diabetes have an increased risk of impaired fracture healing when compared with patients without diabetes. In addition, fracture healing in the lower extremities, short bones, and osteoporosis-unrelated fractures, is negatively impacted by diabetes.[266]
Emphasis on bone health is important from childhood (e.g., adequate calcium and vitamin D intake, smoking avoidance, regular weight-bearing exercise).[1][48] The American Diabetes Association advises that older adults should be assessed for fracture risk as part of their routine diabetes care, according to risk factors and comorbidities.[1] A dual-energy x-ray absorptiometry (DEXA) scan every 2-3 years is recommended for older adults (ages >65 years) and younger people with multiple risk factors.[1] Those with low bone mineral density (T-score ≤-2.0) or with previous fragility fractures should be considered for bone protection agents (e.g., antiresorptive or osteoanabolic drugs).[1] Steps should be taken to reduce the risk of falls, including individualizing glycemic goals for those at elevated fracture risk and avoiding hypoglycemia.[1]
International Society for Pediatric and Adolescent Diabetes guidelines do not recommend regular bone densitometry in children and adolescents, though they advise that bone health assessment may be considered when there are certain additional risk factors (e.g., celiac disease or family history of early osteoporosis).[48] Screening for vitamin D deficiency should be considered, especially in high-risk groups and those with darker skin tone.[48]
Periodontal disease is almost twice as common in people with type 1 diabetes than in the general population.[267] Poor glycemic control is associated with increased risk of future tooth loss.[48] Dental caries are also associated with type 1 diabetes.[268][269] People with diabetes should be referred for a dental exam at least once per year.[1] The American Diabetes Association (ADA) recommends that dental health professionals should be included in the diabetes care team, and that early detection of oral health problems by clinicians may be helpful to promote prompt referral to dental care and mitigate the expensive and extensive procedures needed to treat advanced oral disease.[1] Clinical assessment of people with diabetes should include a dental history, and dental professionals should be informed about key aspects of the person’s health and diabetes treatment plan, including glycemic goals, drugs, and comorbid conditions. It is important for dental professionals to know when people with diabetes have high HbA1c levels, as this population may have lower oral healing capacity.[1]
Coordination between dental professionals and the diabetes care team is especially important for people treated with insulin, who are at risk of hypoglycemia during dental procedures, especially if fasting.[1] The risk of hypoglycemia can be mitigated by coordination between the dentist and treating clinician prior to the procedure to make a hypoglycemia prevention plan, which may include drug adjustment, blood glucose monitoring before and during the procedure, and treatment of hypoglycemia if appropriate.[1] Dental professionals caring for people with diabetes should have access to blood glucose monitors during procedures as well as carbohydrates and glucagon to treat any hypoglycemia that occurs.[1]
Sexual dysfunction is common in patients with type 1 diabetes. The most common sexual dysfunction in men is erectile dysfunction (ED).[1] One meta-analysis reported an ED prevalence of 42% globally among men with type 1 diabetes.[275] The risk was significantly influenced by age, type 1 diabetes duration, body mass index, HbA1c, retinopathy, and smoking habits.[275] Other risk factors associated with ED in men with diabetes are peripheral or autonomic neuropathy, cardiovascular disease, hypogonadism, and diuretic therapy.[1] Physical activity may be protective.[1] Men with diabetes and ED report a significant decline in quality-of-life measures and an increase in depressive symptoms, and depression is a well-recognized risk factor for ED. Given the bidirectional relationship between ED and depression, treatment of either one can result in improvement in the other condition.[1] The American Diabetes Association (ADA) recommends screening for ED in men with diabetes, particularly in those with high cardiovascular risk, retinopathy, cardiovascular disease, chronic kidney disease, peripheral or autonomic neuropathy, longer duration of diabetes, depression, and hypogonadism, and in those who are not meeting glycemic goals.[1] First-line therapy for ED in men with diabetes is phosphodiesterase-5 (PDE5) inhibitors, but men with diabetes may be less responsive than men without diabetes.[1] Strategies to improve response to PDE5 inhibitors include daily therapy and optimization of comorbidities. In men with diabetes not responding to PDE5 inhibitors, other potentially effective treatments may include intracavernosal injections, intraurethral prostaglandin, vacuum erection devices, and penile prosthetic surgery.[1]
Female sexual dysfunction (FSD) is a common problem in women with diabetes, with patients reporting problems with libido, arousal, orgasm, lubrication, and pain.[1] While studies showing the association between diabetes and FSD are less conclusive than those in men, most have reported a higher prevalence of FSD in women with diabetes compared with women without diabetes.[1] One meta-analysis found that FSD was more than twice as common in women with type 1 diabetes than in women without diabetes (odds ratio [OR] 2.27).[276] The ADA recommends screening women with type 1 diabetes for problems with libido, arousal, and orgasm, particularly those who experience depression and/or anxiety and those with recurrent urinary tract infections.[1] In postmenopausal women with diabetes or prediabetes, healthcare professionals should screen for symptoms and/or signs of genitourinary syndrome of menopause, including vaginal dryness and dyspareunia.[1]
Several medical conditions increase the risk of FSD in women with diabetes, including hypertension, obesity, metabolic syndrome, smoking, high cholesterol, depression, anxiety, and diabetes distress.[1] The presence of diabetic retinopathy and neuropathy for an extended period, difficulty in achieving target blood sugar levels, and presence of menopausal symptoms are also risk factors.[1] There are no specific treatment guidelines for FSD in women with diabetes, but a general recommendation is to encourage patients to adopt healthier lifestyle habits; the Look AHEAD study showed that lifestyle interventions can significantly improve overall sexual function and specific aspects of sexual dysfunction in these women. Key lifestyle changes that can positively impact sexual desire and function include following a nutritious diet (like the Mediterranean diet), regular exercise (such as walking), and quitting smoking.[1] Other interventions recommended by the ADA include improving glycemic management and and preventing diabetes-related complications; managing menopausal symptoms with hormonal therapies; treating vaginal dryness, painful intercourse, and genital infections; screening for and treating mental health issues such as depression, anxiety, and diabetes-related distress; and considering drugs for hypoactive sexual desire disorder, such as flibanserin and bremelanotide, when appropriate.[1]
A disability is defined as a physical or mental impairment that substantially limits one or more major life activities of an individual.[1] Diabetes is associated with an increase in the risk of work and physical disability, with estimates of 50% to 80% increased risk of disability for people with diabetes compared with people without diabetes.[277] The mechanisms underlying disability are multifactorial and include coronary artery disease, stroke, lower extremity complications (e.g., peripheral neuropathy, peripheral vascular disease, and amputation), visual impairment due to retinopathy, obesity (where present; more relevant for type 2 diabetes), and physiologic factors such as hyperglycemia, sarcopenia, inflammation, and insulin resistance.[1] If a disability is impacting functional ability or capacity to manage their diabetes, a referral should be made to an appropriate healthcare professional specializing in disability (e.g., physical medicine and rehabilitation specialist, physical therapist, occupational therapist, or speech language pathologist).[1] Older adults in particular may require increased support, and should be screened for geriatric syndromes (e.g., cognitive impairment, depression, urinary incontinence, falls, persistent pain, and frailty), and for polypharmacy, which can negatively impact on self-management and quality of life.[1] Screening at least annually for cognitive impairment is recommended by the ADA for those ages 65 years and over.[1]
Type 1 diabetes is a risk factor for rapid cognitive decline. In one study, patients with >50 years duration of type 1 diabetes performed worse on immediate and delayed recall, and psychomotor speed, as compared with similar-age people without diabetes.[261] A 32-year follow-up of people with type 1 diabetes enrolled in the DCCT/EDIC study showed that poorer diabetes control was associated with more rapid decline of cognitive function. Exposure to higher HbA1c, more episodes of severe hypoglycemia, and elevated systolic blood pressure together accounted for 9.4 years of advanced aging.[262] Control of cardiovascular risk factors in addition to glycemia can help to reduce the risk of dementia.[1]
Decline in cognitive functioning can affect diabetes self-management (e.g., accidental skipped meals and incorrect insulin-dosing increasing risk of hypoglycemia) and make meeting treatment goals challenging.[1] Increased support with diabetes management and simplified treatment plans should be considered for those with cognitive decline/impairment, as well as increased vigilance for hypoglycemia (as there is a bidirectional association between cognitive impairment and hypoglycemia).[1]
Growing evidence documents that children and adolescents with type 1 diabetes are more at risk for pathophysiologic brain changes and neurocognitive deficits than healthy peers.[48] Youth with diabetes are at risk for specific neurocognitive deficits such as information processing difficulties (attention, memory, processing speed), learning disabilities and problems with executive functions (such as goal-oriented behavior and other key skills for self-management such as planning, problem-solving and organization).[48] Executive function deficits can make diabetes self-management more difficult, potentially leading to worsening glycemic outcomes and resulting in a dysfunctional cycle of further brain injury and even greater neurocognitive function deficits. Additionally, worse executive functions are linked to lower quality of life and mental health problems.[48] According to the International Society for Pediatric and Adolescent Diabetes (ISPAD), hypoglycemia, hyperglycemia, and diabetic ketoacidosis (DKA), especially if recurrent, can impact school functioning and educational attainment via a combination of mechanisms including altered cognitive function and nonattendance for acute treatment; however, it notes that findings regarding the impact of type 1 diabetes on academic performance in young people are mixed.[48] Studies identified have early disease onset and factors experienced around onset (higher HbA1c, severe hypoglycemic events, and DKA) as major contributors to initial cognitive decrements, with no or limited decline in cognitive abilities if these are experienced later after diagnosis. It is hypothesized that these early disease factors provide an “initial strike”, after which the brain adapts to the new situation of fluctuating glucose levels.[48] Research also suggests that low time in range (TIR) negatively impacts brain development in young people with type 1 diabetes.[263]
Impairment in hearing is more common in people with diabetes (with stronger associations found in younger people) and occurs across a range of frequencies.[1] A National Health and Nutrition Examination Survey (NHANES) analysis found it to be around twice as prevalent in those with diabetes after adjusting for age and other risk factors.[271] Reported risk factors in diabetes are low HDL-cholesterol, coronary heart disease, peripheral neuropathy, and general poor health.[1] A link between glucose levels and hearing loss has not consistently been demonstrated.[1]
The incidence and prevalence of heart failure is reported to be up to three times higher in patients with diabetes than in those without diabetes.[245][246] There is also a two to five times higher crude incidence rate of heart failure hospitalization and mortality for those with type 1 diabetes compared with those without diabetes, and a higher prevalence of diastolic dysfunction.[247][248] One systematic review of over 12 million global participants revealed that heart failure may be even more prevalent among adults with type 1 diabetes than those with type 2 diabetes.[249] The American Diabetes Association recommends screening adults with diabetes for heart failure by measuring B-type natriuretic peptide [BNP] or N-terminal prohormone B-natriuretic peptide [NT-proBNP]), followed by echocardiography if positive, and using an interprofessional approach (with cardiovascular expertise) to optimize medical therapy for those with asymptomatic (stage B) heart failure to reduce the risk of progression to symptomatic (stage 3) disease.[1]
Diabetes is a risk factor for development and progression of PAD. The risk is proportional to the severity and duration of diabetes. The UK Prospective Diabetes Study Group showed that each 1% increase in HbA1c levels is associated with a 28% increased risk of incident PAD and with a 28% increased risk of death, independent of other variables, such as blood pressure, serum cholesterol, age, or smoking status. Thus, aggressive control of hyperglycemia is essential to prevent disease progression and reduce cardiovascular risk.[250][251]
The presence of diabetes during pregnancy significantly increases the risk of adverse maternal and fetal outcomes, with hyperglycemia and preexisting diabetic complications serving as key contributing factors.[1] Specific risks of diabetes in pregnancy include spontaneous abortion, fetal anomalies, preeclampsia, fetal demise, macrosomia, neonatal hypoglycemia, neonatal hyperbilirubinemia, and neonatal respiratory distress syndrome.[1][272] In addition, exposure to hyperglycemia in utero increases the risks of obesity, hypertension, and type 2 diabetes in offspring later in life.[1]
Optimal control of diabetes before and during pregnancy is associated with lower risk of adverse maternal and neonatal outcomes. One meta-analysis found that automated insulin delivery systems can significantly improve nocturnal glycemic control and potentially reduce glycemic variability in pregnant women with type 1 diabetes, with no impact on the risk of hypoglycemia and hyperglycemia compared with standard care (use of sensor-augmented pumps and multiple daily insulin injections).[273] Addressing maternal body mass index (BMI) prepregnancy and preventing excessive gestational weight gain have also been shown to improve outcomes; in one meta-analysis, preconception BMI ≥ 25 kg/m² or excessive gestational weight gain was associated with a 22% and 50% increase, respectively, in perinatal complications.[274]
Pregnancy is a ketogenic state, and people with type 1 diabetes are at risk for diabetic ketoacidosis (DKA) at lower blood glucose levels than in the nonpregnant state.[1] They should be advised to obtain ketone test strips and receive education on DKA prevention and detection. DKA carries a high risk of stillbirth.[1] In the third trimester, patients experiencing DKA and unable to eat often require intravenous 10% dextrose combined with an insulin infusion to meet the increased carbohydrate demands of the placenta and fetus, thereby facilitating resolution of ketosis.[1]
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