Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities

INTRODUCTION — 

Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in childhood. It is caused by insulin deficiency resulting from the autoimmune destruction of insulin-producing pancreatic beta cells. Lifelong insulin replacement is the treatment for T1DM. The goal of insulin therapy is to maintain blood glucose within target ranges, as measured by hemoglobin A1C (A1C). Maintaining A1C at or below target has been shown to reduce the risk of microvascular complications (retinopathy, nephropathy, and neuropathy) among adolescents [1] and risk of macrovascular complications (atherosclerosis, myocardial infarction, peripheral artery disease, and stroke) in adulthood [2,3].

Medical and psychosocial comorbidities (eg, autoimmune thyroid disease, celiac disease, mood disorders, and eating disorders) significantly impact diabetes management and quality of life for patients with T1DM.

The approach to identifying and managing comorbidities and complications of T1DM is reviewed here. Other aspects of T1DM in children are discussed separately:

●(See "Pathogenesis of type 1 diabetes mellitus".)

●(See "Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents".)

●(See "Overview of the management of type 1 diabetes mellitus in children and adolescents".)

●(See "Type 1 diabetes mellitus in children and adolescents: Insulin therapy".)

●(See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia".)

●(See "Diabetic ketoacidosis in children: Clinical features and diagnosis".)

●(See "Diabetic ketoacidosis in children: Treatment and complications".)

ACUTE GLYCEMIC COMPLICATIONS — 

Beginning immediately after diagnosis, routine outpatient visits for youth with T1DM should include a comprehensive assessment of glycemic trends, insulin administration, and barriers to optimal glycemic control (table 1).

Hypoglycemia — Hypoglycemia is the most common acute complication of T1DM in childhood. Severe and recurrent hypoglycemia can lead to acute and permanent neurologic complications. The symptoms, risk factors, clinical manifestations, and management of hypoglycemia in children and adolescents with T1DM are discussed in detail separately. (See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia".)

Acute complications associated with hyperglycemia

Diabetic ketoacidosis — Without insulin therapy, patients with T1DM develop diabetic ketoacidosis (DKA), characterized biochemically by hyperglycemia and metabolic acidosis and clinically by dehydration, nausea/vomiting, tachypnea, and altered consciousness [4]. DKA is common and life-threatening if not treated promptly. It may be the initial presentation of T1DM or occur in a patient with known diabetes, precipitated by insulin omission or inadequate insulin dose in the setting of increased insulin resistance (eg, illness). The presentation, clinical features, diagnosis, and management of DKA are discussed separately. (See "Diabetic ketoacidosis in children: Clinical features and diagnosis" and "Diabetic ketoacidosis in children: Treatment and complications" and 'Mortality' below.)

Hyperosmolar hyperglycemic state — Hyperosmolar hyperglycemic state (HHS) is rare in patients with T1DM. HHS is a severe metabolic disturbance associated with marked hyperglycemia and minimal acidosis, characterized clinically by dehydration and altered consciousness. Although patients with T1DM rarely present with HHS, rapid identification and treatment of this disorder is essential to prevent coma and death. A large retrospective review of more than 500,000 patients with diabetes (type 1 and type 2) identified HHS at diabetes diagnosis in 0.4 percent of pediatric patients with T1DM at a median age of 7.5 years. In the same study, no significant differences were noticed between the patients presenting at diagnosis with HHS and those with DKA with respect to age, hemoglobin A1C (A1C), or sex [5]. (See "Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis", section on 'Diagnostic evaluation'.)

CHRONIC COMPLICATIONS: SCREENING AND MANAGEMENT — 

Routine outpatient visits for youth with T1DM should include timely screening for T1DM comorbidities and complications (table 1).

There is no single correct approach to screening for chronic complications in patients with T1DM. The American Diabetes Association (ADA) and the International Society for Pediatric and Adolescent Diabetes (ISPAD) periodically issue consensus guidelines on screening and management that are similar but not identical [6-8]. In most instances, our approach agrees with society guidelines. However, we attempt to individualize screening and management of T1DM-related complications based on patient characteristics and available resources. Our approach is outlined below.

Impaired growth velocity — Height, weight, and body mass index (BMI) should be monitored carefully every three to six months and plotted on growth charts (table 1). Starting at age eight to nine years (or earlier if puberty has started), physical examination with Tanner staging should be performed at least yearly. (See "Measurement of growth in children" and "Normal puberty".)

Most children with T1DM grow normally [9]. However, inadequate adherence to insulin treatment has been associated with a risk of mildly decreased growth velocity as well as delayed pubertal maturation in several cohort studies [10-12]. Attrition of linear growth and delayed puberty should prompt a review of glycemic data and adherence to insulin regimen in addition to clinical evaluation to rule out other causes of altered growth and development. (See "Diagnostic approach to children and adolescents with short stature" and "Delayed puberty: Approach to evaluation and management".)

Rarely, children and adolescents with T1DM and inconsistent adherence to insulin therapy develop Mauriac syndrome, which is characterized by growth failure, delayed puberty, and hepatomegaly with serum transaminase elevation and lactic acidosis [13,14]. Mauriac syndrome is caused by excessive hepatic glycogen storage induced by episodes of hyperglycemia alternating with supraphysiologic insulin levels [15-17]. However, most patients with T1DM who use insulin inconsistently do not develop growth failure or hepatomegaly, suggesting a role for genetic risk in the pathogenesis of Mauriac syndrome [18,19]. Catch-up growth generally occurs if glycemic control is restored. Some individuals who are quickly restored to euglycemia may have a paradoxical worsening of existing retinopathy. Patients with features of Mauriac syndrome should be followed closely as metabolic control is established [15-17,20].

Weight changes — Height, weight, and BMI should be monitored regularly, as described above (table 1).

Weight loss — Unintentional weight loss is common before T1DM diagnosis. Most patients regain weight within six months of diabetes diagnosis if insulin replacement therapy is appropriate for the patient's needs [21]. Therefore, persistent weight loss >6 months after diabetes diagnosis requires additional evaluation.

Weight loss may be caused by insufficient insulin replacement, excess energy expenditure (eg, from hyperthyroidism-induced hypermetabolic state or as a consequence of excessive exercise), insufficient caloric intake, or impaired nutrient absorption (eg, celiac disease). (See 'Evaluation and management' below.)

Weight gain — Rapid weight gain may occur immediately after diagnosis of T1DM following initiation of insulin therapy, although it can occur at any time. The prevalence of overweight and obesity among youth with T1DM has roughly paralleled that of the general pediatric population in the last 30 years, but the evaluation and treatment of weight gain among patients with T1DM presents unique challenges [22-26]. In pediatric cohorts with T1DM, longer duration of diabetes and higher insulin doses have been associated with higher BMI, suggesting that intensive insulin treatment may itself be associated with weight gain. Several explanations have been proposed for the effects of insulin therapy on weight, including avoidance of exercise due to concerns about hypoglycemia [27,28] and consumption of high-glycemic index foods to treat and prevent hypoglycemia. In a prospective cohort study of youth with T1DM, increased adiposity was not associated with increased frequency of hypoglycemia [26,29].

BMI >95^th percentile and central adiposity have been associated with increased risk of micro- and macrovascular complications in patients with T1DM, although it is unclear whether this effect is independent of insulin resistance [30-38]. (See 'Vascular disease' below.)

Evaluation and management — The clinical evaluation of weight gain and weight loss in patients with T1DM includes a thorough history and physical examination, a review of glycemic data and insulin administration, dietary history, and a review of physical activity. Management may involve insulin dose adjustment and/or additional pharmacotherapy for weight management.

●Review of symptoms, history, and physical examination – In patients with T1DM, a thorough history, symptom review, and physical examination may provide vital information about the cause of poor growth and/or weight changes. Symptoms may suggest the need for further laboratory evaluation (eg, a patient with weight loss, bloating, and abnormal stooling should undergo laboratory testing for celiac disease). (See "Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus" and "Evaluation of weight loss in infants over six months of age, children, and adolescents".)

●Review of glycemic data and adjustment of insulin regimen – The most likely cause of unexpected weight changes in patients with T1DM is inappropriate estimation of insulin needs. In a large international cross-sectional cohort study of youth with T1DM, both underweight and overweight children were more likely to have hemoglobin A1C (A1C) above target than children of normal weight [23]. Therefore, weight changes should prompt an assessment of glycemic trends.

•Hyperglycemia may be a result of insulin omission or inadequate insulin doses. Hyperglycemia may lead to weight loss or inability to appropriately gain weight because of chronic glucosuria and increased turnover of fat and muscle.

•Hypoglycemic events may indicate that insulin doses are excessive. Insulin drives weight gain by stimulating lipogenesis. Insulin doses may be excessive if the insulin regimen has not been adjusted in response to increased insulin sensitivity (eg, during the honeymoon period following T1DM diagnosis or after puberty) [39,40]. In other cases, patient or caregiver fears about hypoglycemia lead to excessive consumption of fast-acting carbohydrates, resulting in weight gain due to caloric excess. In such cases, clinicians should provide patients and caregivers with clear blood glucose thresholds at which to treat hyperglycemia and hypoglycemia. Additional counseling should focus on the appropriate use of carbohydrate-dense foods (eg, immediately before, during, or after exercise). (See "Management of type 1 diabetes mellitus in children during illness, procedures, school, or travel", section on 'Supportive care' and "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia", section on 'Fear of hypoglycemia' and "Type 1 diabetes mellitus in children and adolescents: Insulin therapy", section on 'Insulin management for special situations'.)

●Review of diet and physical activity – A thorough assessment of the patient's dietary history and patient/caregivers' understanding of nutritional needs should be part of the routine care of youth with T1DM. In our center, a registered dietician meets with patients at least annually (and more often if there are weight or nutrition-related concerns). Individualized medical nutrition therapy should focus on individual food behaviors and include counseling about the differential glycemic and metabolic effects of carbohydrate, fat, and protein [6]. (See "Dietary history and recommended dietary intake in children" and "Overview of the management of type 1 diabetes mellitus in children and adolescents".)

In patients with weight gain, we inquire about fear of hypoglycemia and its impact on decisions about diet and physical activity. Diabetes care teams should ensure that patients and caregivers understand how to manage insulin and blood glucose during exercise and invite them to participate in developing and adapting plans to their family's particular needs. (See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia", section on 'Fear of hypoglycemia' and "Type 1 diabetes mellitus in children and adolescents: Management of exercise", section on 'Glycemic management during exercise'.)

In patients with weight loss, we ask about restrictive or avoidant eating behaviors. This is discussed in detail elsewhere. (See 'Psychosocial comorbidities' below and "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Screening'.)

●Pharmacotherapy for weight gain – Metformin can be used for the limited indication of managing obesity in children with T1DM. Glucagon-like peptide-1 (GLP-1) receptor agonists are effective weight loss agents and can be used for the management of obesity in individuals with T1DM who are 12 years and older. (See "Prevention and management of childhood obesity in the primary care setting".)

However, metformin and GLP-1 receptor agonists (eg, semaglutide, liraglutide) should not be used for blood glucose management in patients with T1DM.

Medications for weight management should only be considered in patients with persistence of BMI ≥95^th percentile after optimization of the insulin regimen, nutrition plan, and physical activity routine. Before considering these medications, clinicians must assess the risk of diabetic ketoacidosis (DKA) (eg, frequency of prior episodes of DKA or ketosis), risk of kidney impairment, and the patient's/caregivers' ability to effectively communicate with the diabetes care team regarding glycemic trends and potential side effects. Clinicians should counsel patients on the likelihood that insulin needs will decrease after weight loss and develop a clear plan for communicating insulin doses to prevent hypoglycemia. (See "Type 1 diabetes mellitus in children and adolescents: Insulin therapy", section on 'Based on long-term glycemic trends (A1C)'.)

Vascular disease

Risk factors for all vascular complications — T1DM is associated with an increased long-term risk of microvascular complications (diabetic kidney disease [DKD], retinopathy, and neuropathy) and macrovascular complications (myocardial infarction, stroke, and coronary and peripheral artery disease) [41-48]. Risk factors for both micro- and macrovascular complications include the following:

●Hyperglycemia – In adolescents and adults with T1DM, randomized trials have established that chronic hyperglycemia is causally associated with microvascular disease and is highly correlated with the risk of macrovascular disease [1,3,24,49,50]. Even modest elevations in A1C (7.0 to 8.5 percent) have been associated with increased risk of albuminuria and retinopathy [1,42,49,51-56] and with a risk of earlier development of coronary artery disease [57]. Glycemic variability has also been shown to increase the risk of albuminuria and retinopathy among adolescents with T1DM [58].

The mechanism by which hyperglycemia predisposes to vascular disease is incompletely understood. Proposed mechanisms include accumulation of advanced glycation end products combined with end-organ responses that include activation of cytokines and protein kinase C. (See "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Pathogenesis'.)

●Other risk factors – Additional risk factors for vascular complications include longer duration of diabetes, earlier puberty, male sex, hypertension, hyperlipidemia, obesity, and lifestyle factors (eg, smoking, infrequent exercise) [49,55,57,59-61]. Insulin resistance may mediate the effects of some of these risk factors (eg, obesity) [62,63].

Genetic susceptibility likely explains some of the heterogeneity in the timing and severity of vascular complications in patients with T1DM [55,64]. Several studies identify higher risk of vascular disease among racial minority youth due in large part to factors attributable to disparities in access to health care, resulting in more severe hyperglycemia at diagnosis and throughout the disease course [65-67].

Measures to reduce risk of all vascular complications — Although vascular complications typically become clinically apparent in adulthood, their pathogenesis begins at disease onset. In most patients diagnosed with T1DM in adolescence, more intensive glycemic management has been shown to lower the long-term risk of microvascular and macrovascular complications [1,68-71]. This protective effect appears to persist into adulthood even when glycemic goals are relaxed [1]. Optimizing glycemic management in childhood is likely to have similar benefits. (See "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Microvascular disease' and "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Benefits of intensive glycemic control'.)

Clinicians caring for children and adolescents with T1DM can mitigate the risk of vascular disease using the following strategies:

●Safely minimize hyperglycemia (maintain A1C at or below age-recommended targets without frequent hypoglycemia).

●Provide counseling on lifestyle factors that contribute to cardiovascular disease (CVD; eg, avoidance of smoking and vaping, regular exercise).

●Identify and address vascular complications early in the disease course (table 1). Although most individuals with T1DM do eventually develop vascular complications, early identification of vascular disease may, in some cases, allow for interventions to slow or halt the progression of DKD, retinopathy, neuropathy, and CVD.

Kidney disease

How to screen — In most patients, we initiate screening for DKD at age ≥10 years or once puberty has started (whichever is earlier), beginning five years after diabetes diagnosis (algorithm 1). We begin screening earlier (as soon as two years after diabetes diagnosis) in patients with evidence of persistent hyperglycemia (eg, A1C persistently above goal, recurrent DKA in the preceding year, or other vascular complications). This is consistent with ADA guidance [6]. ISPAD guidelines recommend initiating screening at age 11 years or with diabetes for two to five years [7].

We measure urine albumin-to-creatinine ratio, typically using a random or "spot" urine sample. A first-morning urine sample is preferable if it can be conveniently collected. We repeat the test at least yearly (table 1). We also measure serum creatinine (with computation of estimated glomerular filtration rate [eGFR]) yearly [6,7,72,73]. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus", section on 'Detection'.)

●<30 mg albumin/g creatinine (3.4 mg/mmol) – A urine albumin-to-creatinine ratio <30 mg albumin/g creatine is normal. Continue annual screening.

●≥30 mg albumin/g creatinine (3.4 mg/mmol) – If the urine albumin-to-creatinine ratio is elevated, repeat the test on a morning sample (or random sample if a morning sample is not possible). Transient elevations in urinary albumin excretion are common in pediatric patients, and a first-morning urine sample can eliminate exercise-induced or orthostatic albuminuria (see "Orthostatic (postural) proteinuria"). Other possible reasons for elevated urinary albumin include fever, menstrual bleeding, urinary tract infection, or marked hyperglycemia [7].

If the urine albumin-to-creatinine ratio is normal on a second sample, a third sample should be obtained three months after the second sample. Ideally, the third urine sample should be obtained after confounding causes of albuminuria (eg, illness, menstruation) have resolved. If the urine albumin-to-creatinine ratio is elevated in at least two of three samples obtained within three to six months, moderately increased albuminuria is likely.

Moderately increased albuminuria (formerly known as microalbuminuria) is defined as persistent urine albumin-to-creatinine ratio of 30 to 299 mg albumin/g creatinine after nondiabetes-related kidney disease has been excluded. Severely increased albuminuria (formerly known as macroalbuminuria) is defined as a urinary albumin excretion >300 mg albumin/g creatinine.

If glycemic management is good (eg, A1C is 7 to 7.5 percent or below), we evaluate for other causes of proteinuria (eg, nephrotic syndrome) and refer to pediatric nephrology. (See "Evaluation of proteinuria in children".)

Treatment — The treatment of pediatric and adolescent patients with T1DM and moderately increased albuminuria includes good glycemic control, blood pressure management, and pharmacotherapy with an angiotensin-converting enzyme inhibitor (ACEi) or, if ACEi is not tolerated, an angiotensin receptor blocker (ARB) [74].

●Choice of medication – For pediatric and adolescent patients with T1DM and moderately increased albuminuria, irrespective of the presence of hypertension, we initiate an ACEi, such as enalapril or lisinopril. ACEi are effective in reversing albuminuria and overt nephropathy in adults, though there is less evidence for benefit in pediatric patients. In a randomized trial in which adolescents with T1DM were treated with ACEi, statin, ACEi plus statin, or placebo, ACEi did not reduce albumin excretion as measured by the albumin-to-creatinine ratio during the two- to four-year study period. However, this finding may have been limited by the short duration of follow-up [75]. (See "Treatment of diabetic kidney disease".)

●Dosing and administration – We use lisinopril or enalapril based on local availability. Adult dosing of ACEi can be used in older adolescents and young adults who have completed linear growth. The goal of treatment is to normalize albumin excretion. If moderately increased albuminuria persists after three to six months of ACEi treatment at target dose, nephrology consultation is warranted. This is discussed in more detail elsewhere. (See "Treatment of diabetic kidney disease", section on 'Severely increased albuminuria: Treat with angiotensin inhibition'.)

●Counseling for patients on ACEi – ACEi are generally well tolerated, with few side effects at low doses [76]. Because these medications are teratogenic, we provide counseling on contraception for patients who are sexually active and have the potential to become pregnant. If such patients are unable to reliably use contraception, we avoid these medications. In patients who cannot tolerate ACEi, we use ARBs. ARBs also require appropriate reproductive counseling due to potential teratogenicity.

We do not use ACEi and ARBs for primary prevention of nephropathy in patients who are normotensive and do not have albuminuria. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus", section on 'ACE inhibitors or ARBs'.)

Clinical course — Moderately increased albuminuria represents the earliest stage of DKD, which, if untreated, may progress to severely increased albuminuria. Severely increased albumin excretion is defined as persistent excretion greater than 300 mg/day or 200 mcg/min or a urine albumin-to-creatinine ratio greater than 300 mg/g of creatinine.

In patients with T1DM, moderately increased albuminuria may develop in adolescence. In three large European cohorts, moderately increased albuminuria was described within five years of T1DM diagnosis; the prevalence at 15 years ranged from 10.6 to 25.7 percent [51,77-79]. Albuminuria spontaneously resolves in approximately 40 percent of adolescents with T1DM who develop moderately increased albuminuria. However, albuminuria may reoccur during adolescence, and onset during adolescence is associated with an increased risk of DKD in adulthood [79,80]. In the remaining patients, albuminuria will either persist without progression or progress to severely increased albuminuria and/or chronic kidney disease in adulthood. The estimated rates of progression vary across multiple studies. In a large cohort study from Finland with 25-year follow-up, the rate of progression from moderately to severely increased albuminuria was 44.3 percent, and the 10-year cumulative progression rate from severe albuminuria to kidney failure was 28 percent [77,81]. End-stage kidney disease was relatively rare in a Norwegian cohort of 7000 patients diagnosed with T1DM in childhood, occurring in 0.7 percent of 7000 patients with T1DM at 20 years after diagnosis and 5.3 percent at 40 years after diagnosis [82].

In addition to chronic hyperglycemia, risk factors for the development of moderately increased albuminuria include hypertension and repeated episodes of acute kidney injury occurring during DKA [83-85]. An earlier age of albuminuria development may be a risk factor for progression to severely increased proteinuria and chronic kidney disease [77,81,86]. Genetic variants determine approximately one-third of the overall risk of DKD [86]. Specific rare genetic variants appear to contribute to the risk of progression to end-stage kidney disease in patients with T1DM [86].

The epidemiology, natural history, and diagnosis of DKD are discussed in detail elsewhere. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus".)

Retinopathy

How to screen — In most patients, we initiate screening for retinopathy at age ≥11 years, beginning five years after diagnosis. We begin screening earlier (as soon as two years after diabetes diagnosis) in patients with hyperglycemia (eg, A1C persistently above target) and/or inadequate insulin adherence (eg, recurrent DKA). This is consistent with ADA guidance [6]. ISPAD recommends initiating retinopathy screening two to five years after diabetes diagnosis [7].

Screening for retinopathy can be performed with a dilated ophthalmologic examination or retinal photography [6,7]. While either technique is acceptable, automated retinal photography does not require dilation of the eyes and thus may be preferable for some patients. A funduscopic examination without dilation of the pupils is not sufficient to screen for diabetic retinopathy (table 1) [6,7,72].

This examination generally should be repeated every two years; less frequent examinations may be acceptable if recommended by the child's eye care professional based on risk factor assessment, including an A1C persistently <8 percent. (See "Diabetic retinopathy: Screening".)

Screening is mandated in order to detect early retinal changes, which may be reversible [87,88]. Screening also identifies patients with more advanced disease that may be amenable to additional therapy to prevent further progression of disease and vision loss.

Treatment — Management of pediatric and adolescent patients with T1DM and retinopathy is focused on preventing progression and potential reversal with good glycemic control, blood pressure management, and, if needed, specific treatments by an ophthalmologist. Ophthalmologic treatments are discussed in greater detail elsewhere. (See "Diabetic retinopathy: Prevention and treatment".)

Clinical course — Early retinal changes may be diagnosed in adolescent and young adult patients with T1DM [88,89]. Estimates of prevalence of retinopathy in adolescents with T1DM vary from 3 to 20 percent. Lower estimates of prevalence in studies from the past two decades are likely a result of improvements in glycemic management with increased use of intensive insulin regimens [90]. Chronic hyperglycemia is the major risk factor for earlier onset of retinopathy. In one large longitudinal cohort, the median disease duration prior to detection of retinopathy was 15.5 years for patients with A1C values ≥7.5 percent compared with 18.3 years for those with A1C values <7.5 percent [90]. Early onset of retinopathy (<5 years after T1DM diagnosis) has been associated with development of proliferative retinopathy independent of hemoglobin A1C [89]. (See "Diabetic retinopathy: Classification and clinical features".)

Neuropathy

How to screen — In most patients, we initiate screening for neuropathy at age ≥10 years, beginning five years after diabetes diagnosis (table 1) [6,7]. We begin screening earlier (as soon as three years after diabetes diagnosis) in patients with hyperglycemia (eg, A1C >7.5 percent) or evidence of inadequate insulin adherence (eg, recurrent episodes of DKA). This is consistent with ADA guidance [6]. ISPAD recommends initiating neuropathy screening two to five years after diabetes diagnosis [7].

In adolescents and children able to accurately report symptoms, we assess for symptoms of neuropathy, including numbness; burning sensation; tingling; and/or increased pain sensitivity in the toes, legs, and feet. We also perform vibration, pinprick, 10 g monofilament sensation tests, and dorsalis pedis and posterior tibial pulses.

Several simple screening tools are available and are discussed in detail elsewhere. (See "Screening for diabetic polyneuropathy", section on 'History and examination'.)

In addition, we assess patients for signs and symptoms of diabetic autonomic neuropathy, which include resting tachycardia, exercise intolerance, constipation, and symptoms of gastroparesis (nausea, vomiting, and early satiety). (See "Diabetic autonomic neuropathy", section on 'Screening' and "Diabetic autonomic neuropathy of the gastrointestinal tract".)

Treatment — Improved glycemia improves nerve function in patients with diabetes. A complete discussion of the treatment of diabetic neuropathy is reviewed in detail elsewhere. (See "Pathogenesis of diabetic polyneuropathy" and "Management of diabetic neuropathy".)

Clinical course — Although symptomatic diabetic neuropathy is uncommon in children and adolescents with T1DM, subclinical impairment of nerve function has been reported in up to 68 percent of pediatric patients [91-97]. In children, both peripheral and autonomic nervous systems can be affected.

●Peripheral polyneuropathy – Impaired peripheral nerve function includes nerve conduction and sensory perception [94-96,98,99]. The earliest evidence of peripheral neuropathy is distal sensory loss (distal symmetric sensorimotor polyneuropathy) affecting a "glove and stocking" distribution, best tested with a 10 g monofilament. Nerve conduction studies, however, demonstrate a higher prevalence of subclinical motor rather than sensory neuropathy [94].

●Autonomic neuropathy – Impaired autonomic function may include abnormal heart rate variability and postural blood pressure control, pupillary adaptation to darkness, and vibratory threshold. Gastroparesis and other gut autonomic abnormalities can present early in adolescents with persistent hyperglycemia [92,93,100]. Puberty is a critical time for the development of diabetic cardiac autonomic dysfunction [98,100]. (See "Diabetic autonomic neuropathy".)

Cardiovascular disease — CVD (including myocardial infarction, coronary artery disease, stroke, peripheral artery disease, and heart failure) develops at a younger mean age in individuals with T1DM compared with the general population and is the primary reason for persistently shorter life expectancy among adults with T1DM [57,101-104]. Hyperglycemia contributes to risk of CVD through multiple mechanisms, discussed in detail elsewhere. (See "Glycemic management and vascular complications in type 1 diabetes mellitus", section on 'Pathogenesis'.)

The approach to reducing long-term risk of CVD involves both rigorous blood glucose management and addressing modifiable CVD risk factors such as hypertension, hyperlipidemia, obesity, and smoking/vaping. Hypertension and hyperlipidemia are more prevalent in children and adolescents with T1DM than in the general population [105-108]. Importantly, at least one of these risk factors for CVD is present at diagnosis in 60 percent of patients with T1DM [65].

Therefore, minimizing the risk of CVD should be a primary goal for clinicians caring for youth with T1DM beginning at diabetes diagnosis. Atherosclerotic changes may be noted as early as in adolescence in patients with T1DM [65,109-111]. However, CVD risk factors remain underdiagnosed and undertreated in many pediatric care settings [108,112]. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children".)

Elevated blood pressure and hypertension

How to screen — In all patients with T1DM, we measure blood pressure at each routine visit for diabetes management (at least every three months) and more often in patients with abnormal results (table 1). It is important to use an appropriate cuff size and attempt to measure using consistent methods, though we recognize this is not always possible in the office setting [113]. (See "Ambulatory blood pressure monitoring in children", section on 'Clinical procedure'.)

Target systolic blood pressure (SBP) and diastolic blood pressure (DBP) as well as thresholds for elevated blood pressure (formerly prehypertension) and hypertension in pediatric patients are defined by the American Academy of Pediatrics (AAP) and American Heart Association (AHA) (table 2) [114]. Age- and height-specific blood pressure percentiles can be determined using a calculator (calculator 1).

Elevated blood pressure should be repeated for confirmation on two subsequent days after it is first detected. If results are inconclusive, ambulatory blood pressure monitoring may be helpful, although it is not required for a diagnosis of hypertension [6,113]. If hypertension is diagnosed, the patient should undergo a basic clinical evaluation to eliminate secondary causes of high blood pressure. (See "Hypertension in children and adolescents: Evaluation".)

Treatment

●Nonpharmacologic intervention – For all children with T1DM in the "elevated blood pressure" (prehypertension) category, we advise improved glycemic management and lifestyle management with a lower sodium diet, weight management strategies, and regular exercise. (See "Hypertension in children and adolescents: Nonemergency treatment", section on 'Lifestyle interventions and management of comorbid conditions' and 'Weight changes' above.)

●Selection of patients for pharmacologic therapy – Data from randomized controlled trials on the benefits of blood pressure control in patients with T1DM are lacking, although a longitudinal cohort study demonstrated that blood pressure above 120/80 mmHg was associated with an increased risk of coronary artery disease in adults with T1DM [115]. Data are lacking on the impact of early blood pressure management (ie, in childhood and adolescence) on cardiovascular risk in patients with T1DM. However, given the association between hypertension and development of DKD [116,117], use of more stringent cutoffs for medical treatment is reasonable.

In pediatric patients with T1DM who have confirmed hypertension (stage 1 or stage 2) (table 2), we initiate pharmacologic treatment simultaneously with lifestyle management and improved glycemic management. This is consistent with ADA and ISPAD guidelines [6,7].

For patients with persistently elevated blood pressure, we advise lifestyle modification and improved glycemic management. We initiate pharmacologic treatment if blood pressure does not normalize after 6 to 12 months of lifestyle modification. This is a somewhat more stringent approach than is presented in the ADA guidelines but is consistent with ISPAD guidance [6,7].

•Medication choice, dose, and counseling – ACEi are generally the first-line medical therapy for blood pressure management.

-In patients with T1DM and confirmed hypertension (stage 1 or stage 2) or elevated blood pressure (prehypertension) persisting after six months of lifestyle intervention, initial dosing of ACEi is the same as in all other pediatric patients. This is discussed in detail elsewhere. (See "Hypertension in children and adolescents: Nonemergency treatment", section on 'Angiotensin-converting enzyme inhibitors'.)

-In patients with elevated blood pressure or hypertension and coexisting albuminuria, we initiate an ACEi simultaneously with lifestyle changes, using the dose of ACEi for treatment of albuminuria [118]. (See 'Treatment' above.)

-For patients with T1DM, the goal of treatment is to decrease blood pressure values below the 90^th percentile and <130/80 for adolescents ≥13 years old [114]. For patients who have both elevated blood pressure and albuminuria, the goal is to monitor and normalize both.

Other antihypertensive agents, including ARBs, can be used if the patient cannot tolerate ACEi (eg, due to cough) or if targeted blood pressure goals are not reached. Before initiating ACEi or ARBs, we provide counseling about the risks of teratogenicity and options for pregnancy prevention in any patients who can become pregnant [118]. Monitoring for pediatric patients on pharmacotherapy for blood pressure management is discussed elsewhere. (See "Hypertension in children and adolescents: Nonemergency treatment", section on 'Follow-up care'.)

Dyslipidemia

How to screen — Our approach to screening is consistent with ADA guidelines [6]. ISPAD recommends initiating dyslipidemia screening at age 11 unless there is a family history of CVD or if family history is unknown [7].

●We obtain a lipid profile shortly after diabetes diagnosis in patients ≥2 years of age. We initiate screening regardless of family history of hyperlipidemia or CVD as patients/caregivers may not be aware of CVD in family members (table 1). A nonfasting lipid panel is acceptable, though this should be repeated in a fasting state if low-density lipoprotein (LDL) or triglycerides (TG) are elevated (eg, LDL >100 mg/dL, TG >150 mg/dL).

●If the profile is within the accepted risk levels (eg, LDL ≤100 mg/dL), we initiate serial testing at 9 to 11 years of age or onset of puberty (whichever is earlier) and repeat every three years.

●If hyperlipidemia is noted, we perform annual monitoring and initiate routine nutritional counseling. If the initial screen is normal but the patient has persistent hyperglycemia (eg, A1C persistently above target), inadequate insulin adherence (eg, recurrent DKA), or other complications such as albuminuria, yearly measurement may be considered [109-111].

Treatment — Hyperglycemia is associated with increased risk of hyperlipidemia, which is, in turn, associated with risk of CVD [107,119,120].

●Nonpharmacologic intervention

•For patients with T1DM and LDL ≥100 mg/dL to 129 mg/dL, we encourage dietary modification, exercise, weight management, and improved glycemic management.

•For patients with LDL ≥130 mg/dL, we encourage nonpharmacologic intervention (nutritional counseling, exercise) and improved glycemic management. If LDL remains elevated after six months in patients 10 years and older, we initiate statins. (See "Dyslipidemia in children and adolescents: Management", section on 'Heart-healthy diet'.)

Structured nutrition and exercise programs may have benefits for patients with T1DM. However, such intensive interventions may not be feasible in all clinical settings [121].

●Selection of patients for pharmacologic therapy – Data from one randomized controlled trial in adults with T1DM demonstrated that treatment with statins was associated with decreased risk of stroke, coronary heart disease, and all-cause mortality [122]. In a randomized controlled trial of atorvastatin therapy for two to four years in adolescents with T1DM, the treated group had lower total LDL and non-high-density lipoprotein (HDL) levels as well as a more favorable ratio of apolipoprotein B to apolipoprotein A1 compared with the untreated group [76]. However, there was no difference between the groups with respect to markers of atherosclerotic disease, such as carotid intima-media thickness [76].

Due to increased cardiovascular risk, the AHA advises simultaneously initiating lifestyle changes and statins in pediatric patients ≥10 years old with T1DM and hyperlipidemia (LDL >130 mg/dL) [123]. However, ADA and ISPAD guidelines recommend a six month trial of lifestyle intervention before initiating statins [6,7]. This guidance is based on observational studies demonstrating beneficial effects from reduced hyperglycemia, nutritional intervention, and exercise on lipid levels [121,124,125].

●Medication choice, dose and counseling – Our approach is in agreement with ISPAD guidance [7].

•If LDL is ≥130 mg/dL after six months of nonpharmacologic interventions, we initiate statins in patients 10 years and older. Approaches to selection of specific agents and initial dosing are the same in patients with and without diabetes. (See "Dyslipidemia in children and adolescents: Management", section on 'Dosing'.)

•Lipid targets for children with diabetes who are on statins (LDL <100 mg/dL, HDL >35 mg/dL, TG <150 mg/dL) are consistent with ADA recommendations [6].

Before initiating statins, we provide counseling about the risks of teratogenicity and options for pregnancy prevention in any patients who can become pregnant. Monitoring of statins is the same in pediatric patients with and without diabetes and is discussed in detail elsewhere. (See "Dyslipidemia in children and adolescents: Management", section on 'Statin therapy'.)

Smoking — Smoking is independently associated with an increased risk of micro- and macrovascular complications in patients with T1DM [126]. We ask about nicotine exposure at each visit and, at minimum, once per year in patients beginning at age 11 or 12. Smoking and vaping cessation counseling is discussed in detail elsewhere. (See "Prevention of smoking and vaping initiation in children and adolescents" and "Management of smoking and vaping cessation in adolescents".)

COMORBID CONDITIONS

Autoimmune diseases — Children and adolescents with T1DM are at increased risk for other autoimmune diseases, the most common being autoimmune thyroiditis and celiac disease. Routine screening for these conditions is recommended for all patients with T1DM at diagnosis and then at variable intervals thereafter (table 1) [6,8]. (See "Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus".)

Psychosocial comorbidities — Patients with diabetes may experience a range of psychosocial concerns (including diabetes distress, depression, and eating disorders), which may be associated with worsening glycemia and increased frequency of hospitalization [127-129]. Caregiver distress is increasingly recognized as an additional factor in glycemic outcomes in pediatric T1DM [130]. In randomized trials, structured psychoeducational support significantly improved glycemia and reduced hospital admission rates in adolescents who previously had inadequate insulin adherence [131-133]. Comprehensive management of diabetes should identify and address psychosocial comorbidities of diabetes in children and adolescents as well as their caregivers.

●Diabetes distress – Diabetes distress describes the constellation of negative emotional responses to living with diabetes, such as frustration, anger, sadness, and anxiety about complications. Diabetes distress is not a psychiatric condition. It is considered an adaptive response to the burden of living with diabetes but is associated with higher hemoglobin A1C (A1C), lower quality of life, and greater risk of major depression in youth with T1DM [134,135]. (See 'How to screen' below.)

●Depression – Depression is the most common psychiatric comorbidity among youth with T1DM and is more prevalent in children and adolescents with diabetes than in the general population [127,128,136-140]. The highest rate of depression occurs in the first year after diagnosis and in adolescents [136,137]. (See 'How to screen' below.)

●Eating disorders – Female adolescents with T1DM are more likely to develop an eating disorder compared with adolescents without diabetes [141-147]. Eating disorders may manifest as weight control practices such as fasting, self-induced vomiting (bulimia), and diuretic abuse as well as the purposeful omission of insulin for weight loss (sometimes referred to as "diabulimia") [148]. A study of adolescents with T1DM in Norway found that nearly one-third reported restricting their insulin dose after overeating [145].

Patients with T1DM and eating disorders have poorer metabolic control, require more frequent hospitalization, and are more likely to develop microvascular complications compared with those without eating disorders [149-153]. They also have an increased mortality rate compared with patients with only diabetes or only an eating disorder [154]. (See "Approach to the adult with brittle diabetes or high glucose variability", section on 'Psychosocial' and 'How to screen' below.)

How to screen — The optimal screening approach depends on the clinical model and available resources. Although many age-appropriate, validated tools exist to screen for common psychosocial concerns in T1DM, the approach is often determined by time available during clinic visits, comfort with interpretation of mental health screening, and the availability of mental health clinicians for referral [6,146,155].

In some diabetes multidisciplinary clinics, mental health professionals perform depression screening at least yearly with the Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) tools. Additional follow-up is individualized based on screening results.

Strategies for psychosocial screening for patients with T1DM include (table 1):

●Diabetes distress – Asking open-ended questions about the impact of diabetes on the child/adolescent's emotional state may allow clinicians to identify diabetes distress. Validated screening tools for diabetes distress also exist for both pediatric patients (eg, Problem Areas in Diabetes Survey-Pediatric Version [PAID-Peds]) [156,157] and caregivers.

●Depression – Validated tools such as the PHQ-2 and PHQ-9 may be used to screen for depression beginning in childhood (approximately age eight). Existing data are inconsistent with respect to the score at which to refer for further mental health evaluation.

One common approach is to administer the PHQ-2 first and then administer the PHQ-9 to patients who have a score of 3 or more, although this reduces sensitivity and may miss some patients [158]. The use of the PHQ-2 to screen for depression is discussed in detail elsewhere. (See "Pediatric unipolar depression: Epidemiology, clinical features, assessment, and diagnosis" and "Screening tests in children and adolescents", section on 'Depression and suicide risk screening'.)

●Eating disorders – We ask general questions about body image (eg, "Since our last visit, have you been trying to gain or lose weight?") in most adolescents. The Diabetes Eating Problems Survey-Revised (DEPS-R) may be used for screening, typically starting at age 10 to 11 years [147]. (See "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Screening'.)

Treatment — Children and adolescents with mental health symptoms or a positive screening test using a validated instrument should be further evaluated by a skilled mental health worker, and, if appropriate, intervention should be initiated [146]. (See "Overview of prevention and treatment for pediatric depression".)

OTHER COMPLICATIONS — 

Other complications in pediatric patients with T1DM are summarized below.

●Metabolic dysfunction-associated steatotic liver disease (MASLD) – Prevalence of MASLD is higher in children and adolescents than in the general population. Hyperglycemia (eg, hemoglobin A1C [A1C] above target) is associated with increased risk of MASLD, which improves when glycemic targets are met [159,160]. (See "Metabolic dysfunction-associated steatotic liver disease in children and adolescents", section on 'Risk factors and comorbidities'.)

●Gastroparesis – (See "Diabetic autonomic neuropathy of the gastrointestinal tract", section on 'Gastroparesis'.)

●Necrobiosis lipoidica diabeticorum – (See "Necrobiosis lipoidica".)

●Limited joint mobility – Limited joint mobility, primarily affecting the hands and feet, may be associated with diabetes. (See "Limited joint mobility in diabetes mellitus".)

●Menstrual irregularities – Menstrual irregularities are common in patients with T1DM. Menstrual irregularities are associated with chronic hyperglycemia and often improve when glycemic management is better [161]. (See "Abnormal uterine bleeding in adolescents: Evaluation and approach to diagnosis".)

●Paronychia – Adolescents with T1DM have a high prevalence of paronychia compared with adolescents without diabetes, which is, in part, a result of impaired vibration sensation [162]. (See "Paronychia" and "Nail disorders in infants and children: Acquired nail diseases".)

●Calcium, vitamin D, and bone changes – Patients with diabetes who have persistent microalbuminuria have lower levels of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and osteocalcin compared with children with diabetes who are normoalbuminuric [163]. They have increased fracture risk and abnormalities in bone microarchitecture, which are detectable in adolescence [164-166]. (See "Bone disease in diabetes mellitus".)

MORTALITY — 

Diabetic ketoacidosis (DKA) is the primary cause of death in children and adolescents with T1DM. This was illustrated in a retrospective review of all deaths in the city of Chicago among children, adolescents, and young adults with T1DM [167]. Among 30 deaths, 20 were attributed to DKA or coincided with the diagnosis of diabetes. Five deaths were attributed to kidney disease and one to hypoglycemia.

Similarly, in a series describing 83 deaths attributed to diabetes among children and adolescents in England, over 80 percent of the deaths were related to hyperglycemia or DKA, and most of the deaths that occurred in hospitals were attributed to cerebral edema [168]. Of note, 41 percent of the patients died at home or were moribund on arrival at the hospital. This highlights other factors contributing to increased mortality in pediatric T1DM. Specifically, hypoglycemia and/or autonomic neuropathy have been identified as the cause of sudden death in 5 to 10 percent of pediatric patients with T1DM [169,170]. These data highlight the importance of preventing overnight hypoglycemia and identifying hypoglycemia unawareness during all patient visits. (See "Diabetic ketoacidosis in children: Treatment and complications", section on 'Complications and mortality' and "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia".)

Multiple studies have identified higher mortality rates among youth with T1DM from minoritized racial groups (non-Hispanic Black and Hispanic patients) in the United States [171,172]. This may reflect socioeconomic disparities as well as institutional racism leading to differences in access to or implementation of comprehensive diabetes care, including use of diabetes technology.

In adults with T1DM, important causes of mortality include vascular complications (such as cardiovascular disease [CVD]) as well as DKA and hypoglycemia. (See "Glycemic management and vascular complications in type 1 diabetes mellitus".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lipid disorders and atherosclerosis in children" and "Society guideline links: Diabetes mellitus in children".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Type 1 diabetes (The Basics)" and "Patient education: Type 1 diabetes in children (The Basics)" and "Patient education: Managing blood sugar in children with diabetes (The Basics)" and "Patient education: Carb counting for children with diabetes (The Basics)" and "Patient education: Managing diabetes in school (The Basics)" and "Patient education: Giving your child insulin (The Basics)" and "Patient education: Checking your child's blood sugar level (The Basics)" and "Patient education: Insulin pumps (The Basics)")

●Beyond the Basics topics (see "Patient education: Type 1 diabetes: Overview (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Acute glycemic complications – Acute complications such as hypoglycemia and diabetic ketoacidosis (DKA) may occur at diagnosis with type 1 diabetes mellitus (T1DM) or anytime thereafter. They require emergent management. (See "Type 1 diabetes in children and adolescents: Prevention and management of hypoglycemia" and "Diabetic ketoacidosis in children: Clinical features and diagnosis" and "Diabetic ketoacidosis in children: Treatment and complications".)

●Chronic complications – Regular screening allows for early identification and management of complications and comorbidities associated with T1DM (table 1). Improved glycemia and other interventions can prevent progression of some long-term sequelae. (See 'Chronic complications: Screening and management' above.)

•Decreased growth velocity and weight changes – Height and weight should be measured every three to six months. Reduced growth and/or weight changes should prompt a clinical evaluation including review of insulin doses and adherence, glycemic data, diet/nutrition, and, if needed, an evaluation for comorbid disorders (eg, autoimmune disease). (See 'Impaired growth velocity' above and 'Weight changes' above.)

•Vascular complications – Vascular complications may develop in adolescence or earlier. Treatment involves adjustment of the insulin regimen and close monitoring to maintain glucose in target range. (See 'Measures to reduce risk of all vascular complications' above.)

•Microvascular complications – Hyperglycemia is the major risk factor for microvascular complications. For most patients, screening for microvascular complications begins five years after T1DM diagnosis (table 1). In patients with persistent hyperglycemia (eg, hemoglobin A1C [A1C] above target) and/or inadequate adherence to insulin regimen (eg, recurrent episodes of DKA), we begin screening <5 years after T1DM diagnosis.

-Diabetic kidney disease (DKD) – Beginning at age 10 or puberty (whichever is first), we measure the urine albumin-to-creatinine ratio annually (algorithm 1). For pediatric and adolescent patients with T1DM and confirmed increased albuminuria (urine albumin-to-creatinine >30 mg albumin/g creatinine [<3.4 mg/mmol] on two of three samples), we suggest improved glycemic management and an angiotensin-converting enzyme inhibitor (ACEi), irrespective of blood pressure (Grade 2C). (See 'Kidney disease' above and "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus", section on 'Treatment'.)

-Retinopathy – Beginning at age 11 years or puberty (whichever is first), we perform in-office fundal photography (or refer for dilated ophthalmologic examination) every two years. (See 'Retinopathy' above.)

-Neuropathy – Beginning at age 10 years or puberty (whichever is first), we screen with a foot examination annually. (See 'Neuropathy' above.)

•Macrovascular complications – Hyperglycemia, hypertension, hyperlipidemia, and smoking/vaping increase risk for cardiovascular disease (CVD; stroke, myocardial infarction, peripheral and coronary artery disease) (table 1).

-Elevated blood pressure of hypertension – We measure blood pressure at least every three months and more often in patients with abnormal results. (See 'How to screen' above.)

For patients with elevated blood pressure (table 2), we advise lifestyle modification (low sodium, exercise, weight management) and improved glycemic management. If elevated blood pressure does not resolve after lifestyle intervention and glycemic management, we suggest treatment with ACEi (Grade 2C). (See 'Treatment' above.)

For patients with confirmed hypertension (table 2), we suggest simultaneous treatment with ACEi rather than lifestyle modification alone (Grade 2C). Dosing is the same in children with and without T1DM. We counsel on teratogenic effects of ACEi and pregnancy prevention. (See 'Treatment' above and "Hypertension in children and adolescents: Nonemergency treatment", section on 'Initial therapy' and 'Elevated blood pressure and hypertension' above.)

-Hyperlipidemia – We obtain a lipid panel soon after T1DM in patients ages two years and up.

In patients <10 years old with low-density lipoprotein (LDL) ≥130 mg/dL, we advise lifestyle modification. (See 'Treatment' above.)

In patients ≥10 years with LDL ≥130 mg/dL, we attempt lifestyle modification and glycemic management. If LDL ≥130 mg/dL persists after lifestyle modification for six months, we suggest statin therapy. Dosing is the same in pediatric patients with and without diabetes. We counsel on teratogenic effects of statins and pregnancy prevention. (See 'Treatment' above and "Dyslipidemia in children and adolescents: Management", section on 'Statin therapy'.)

-Smoking – We ask about smoking and vaping at least yearly in adolescent patients with T1DM and provide counseling on cessation. (See 'Smoking' above.)

●Autoimmune disease – We screen for autoimmune thyroid disease and celiac disease shortly after T1DM diagnosis. We screen for thyroid disease is every one to two years thereafter or if symptoms develop. (See "Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus".)

●Psychosocial concerns – Patients with T1DM should be assessed for psychosocial concerns at least annually, with referral to behavioral health care for patients with clinically significant symptoms identified on screening. (See 'How to screen' above.) Specific screening tools used will depend on practice setting.