1000-2000 5 ьшò

Overall incidence is increasing worldwide.

More cases are diagnosed in the autumn and winter than in spring and summer.

Incidence

18/100,000 per year in the United States (0 to 60/100,000 worldwide) (2)

Average lifetime prevalence risk of T1DM in the general population is 0.4%.

Racial predilection for whites

African Americans have lowest overall incidence.

Pediatric Considerations

Although onset is usually before the age of 19 years, T1DM can occur for the first time in patients who are well into their 30s.

Young children are more likely to present in diabetic ketoacidosis (DKA) due to atypical presentation and because they may not express thirst or obtain fluids as readily as older children or adults.

ETIOLOGYAND PATHOPHYSIOLOGY

Genetic predisposition is thought to exist.

Alteration in immunologic integrity, placing the β-cell at special risk for inflammatory damage

Autoantibodies present in >90% of patients at presentation: glutamic acid decarboxylase (GAD), insulinoma-associated autoantigen 2 (IA2A), zinc transporter 8 (ZnT8A), and insulin (IAA) (2)

Associated environmental triggers (none have been verified):

–Vitamin D deficiency

–Infant feeding practices (short-term breastfeeding, early exposure to complex proteins)

–Viruses (e.g., enteroviruses, retroviruses)

–Environmental toxins

Various epigenetic modifications of gene expression (DNAmethylation, histone modifications, and µ-RNAdysregulation) have been noted, further suggesting a role between genetics and environment in the development of T1DM (3).

Genetics

T1DM is a polygenic disorder with 40+ loci known to affect susceptibility to the disease (2).

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Genes located on major histocompatibility complex (MHC) on chromosome 6 provide about half of the genetic susceptibility leading to T1DM risk (2).

HLAclass II shows the strongest association with T1DM risk, but class I MHCs also affect risk (2).

RISK FACTORS

Certain human leukocyte antigen (HLA) types, MHC classes, and autoantibodies (2)

Increased susceptibility to T1DM is inheritable (3):

–Only 10–15% of newly diagnosed patients with T1DM have a positive family history of T1DM.

–Among autoimmune conditions, T1DM has the highest concordance rates in monozygotic twins.

–Average prevalence risk of T1DM in children of patients with T1DM is ~6%.

–Relative risk for siblings of patients with T1DM is about 15%.

See environmental triggers above (2).

COMMONLYASSOCIATED CONDITIONS

Autoimmune diseases, such as celiac disease, vitamin B12 deficiency, and

Hashimoto hypothyroidism

T1DM can also be seen as part of autoimmune polyendocrine syndromes.

DIAGNOSIS

DIFFERENTIALDIAGNOSIS

Benign renal glycosuria

Glucose intolerance

Type 2 diabetes

Consider monogenic diabetes if

–Diabetes diagnosed before 6 months of age

–Strong family history of diabetes without classic features of type 2 diabetes

–Mild fasting hyperglycemia

–Nonobese diabetic child with negative autoantibodies

Secondary diabetes

–Pancreatic disease (chronic pancreatitis, cystic fibrosis, hereditary hemochromatosis)

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–Endocrine-associated diabetes: acromegaly, Cushing syndrome, pheochromocytoma, glucagonoma, neuroendocrine tumors

–Drugor chemical-induced glucose intolerance: glucocorticosteroids, HIV

protease inhibitors, atypical antipsychotics, tacrolimus, cyclosporine Acute poisonings (salicylate poisoning can cause hyperglycemia and

glycosuria, and may mimic DKA)

DIAGNOSTIC TESTS & INTERPRETATION

Initial Tests (lab, imaging)

Criteria for the diagnosis of diabetes (1)[C]:

–Fasting glucose ≥126 mg/dL(7.0 mmol/L)

–Random of ≥200 mg/dL(11.1 mmol/L) in a patient with classic symptoms of hyperglycemia

–Oral glucose tolerance test; plasma glucose $200 mg/dL 2 hours after a glucose load of 1.75 g/kg (max dose 75 g)

–Glycated hemoglobin (HbA1c) level ≥6.5%

–In the absence of unequivocal hyperglycemia, results should be confirmed

by repeat testing. Other tests to consider:

–Serum electrolytes, especially in sicker patients who may have ketoacidosis

–Urinalysis for glucose, ketones, and microalbuminuria

–Pancreatic autoantibodies

Islet cell, IAA, GAD, IA2A, and ZnT8A

–CBC (WBC count and hemoglobin may be elevated)

C-peptide insulin level if needed to differentiate from type 2 diabetes. Alow level or no C-peptide indicates that the pancreas is producing little or no insulin.

Test Interpretation

Inflammatory changes, lymphocytic infiltration around the islets of Langerhans, or islet cell loss

HISTORY

Polyuria and polydipsia (4)[C]

–Polyuria may present as nocturia, bedwetting, or incontinence in a previously continent child.

–Polyuria may be difficult to appreciate in diaper-clad children.

Weight loss 10–30%

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– Often almost devoid of body fat at diagnosis due to hypovolemia and increased catabolism

Prolonged or recurrent candidal infection, usually in the diaper area

Increased fatigue, lethargy, muscle cramps

Abdominal discomfort, nausea

Vision changes, such as blurriness Altered school or work performance

TREATMENT

GENERALMEASURES

Overall control of carbohydrate metabolism for all pediatric age ranges (1)[C] Education regarding matching of mealtime insulin dose to carbohydrate intake, premeal blood glucose level and anticipated activity (1)

–Before meals, strive for blood glucose levels in range of 90 to 1,300 mg/dL (5.0 to 7.2 mmol/L).

–Bedtime/overnight: 90 to 150 mg/dL (5.0 to 8.3 mmol/L)

–A1c goal: <7.5% across all pediatric age groups

–A1c <7.0% is reasonable if achieved without excessive hypoglycemia.

Very tight control might be dangerous in young children due to risk of repeated hypoglycemia.

Adult A1c goal: <7.0% (1)[B]

–A1c <6.5% reasonable in select individuals (1)[C]

–Less stringent A1c goals (such as <8%) may be appropriate for elderly patients and other special populations (1)[B].

Normal growth and development and overall good health (asymptomatic) (4) [C]:

–Reach optimal height for genetic potential.

–Appropriate and timely pubertal maturation

–Coping psychosocial development: normal school or work attendance and

performance; normal goals/career plans. Screen for depression.

Prevent acute complications, including hypoglycemic insulin reactions and ketoacidosis, and delay or prevent chronic end-organ complications.

MEDICATION

Most patients with T1DM will require insulin supplementation, either multiple-dose insulin (MDI) injections or continuous subcutaneous insulin

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infusion (CSII) (1)[A].

Types of insulin (1)[C]:

–Long-acting insulin analogues: insulin glargine (Lantus/Toujeo), insulin detemir (Levemir), and insulin degludec (Tresiba). These should not be mixed with other insulins in the same syringe.

–Intermediate-acting insulin (NPH)—Humulin N or Novolin N—can be mixed with other insulins.

–Short-acting (regular) insulin: Novolin R or Humulin R

–Very rapid-acting insulin analogues: insulin lispro (Humalog), insulin aspart (Novolog), and insulin glulisine (Apidra)

First Line

Flexible intensive insulin therapy is the gold standard.

MDI or CSII have equal efficacy (1)[B].

Total initial dose is 0.2 to 0.4 U/kg/day for insulin-naïve patients (will often need 0.6 to 0.7 U/kg/day).

40–60% of total dose given as basal insulin, with the rest as bolus insulin MDI regimen (1)[A],(5)[C]:

–Basal, long-acting insulin once or twice a day

–Prandial, short-acting insulin based on number of carbohydrate portions (e.g., 1:10, meaning 1 U of insulin for every 10 g of carbohydrate to be eaten)

–Correctional short-acting mealtime insulin based on premeal blood glucose level (subtract target blood glucose level and divided by sensitivity factor)

CSII regimen:

–May use regular insulin or rapid-acting insulin analogues

–Insulin is infused continuously at a preset rate, and bolus doses are given with meals as above.

Second Line

Twice-daily injections with NPH along with regular or rapid-acting insulin

Not physiologic, but lower cost and fewer injections may improve adherence in the less-motivated patient.

Pramlintide. Delays gastric emptying, increases satiety and weight loss; if used, adjustment of mealtime insulin dose required

Pancreatic transplantation is usually reserved for patients with end-stage renal failure, who may receive kidney-pancreatic transplants at the same time. Oral hypoglycemics generally not indicated in type 1 diabetes

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Ongoing trials with tocilizumab to prevent beta cell loss in type 1 diabetes

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

Newly diagnosed patients with T1DM may require hospitalization during initiation of insulin therapy.

ONGOING CARE

FOLLOW-UPRECOMMENDATIONS

Normal; full participation in sports activities

Regular aerobic exercise is recommended.

Patient Monitoring

Blood pressure (BP) checks at every routine visit with a goal of systolic pressure of <140 mm Hg and diastolic of <90 mm Hg (1)[A]. If elevated, consider an ACE inhibitor or an angiotensin receptor blocker but not both; avoid in pregnancy (1)[B].

Monitor height, weight, and sexual maturation (in children) (5)[C].

Daily home blood glucose monitoring with home blood glucose meter: Blood tests should be done at least 4 to 6 times daily (more frequently in pump patients) for optimal monitoring.

Comprehensive foot exam at least annually

Quarterly measurement of HbA1c

In patients with diabetes and atherosclerotic cardiovascular risk, start high intensity statin in addition to lifestyle changes (1)[A].

Annual screenings (1)[C]:

–Microalbuminuria for earliest signs of possible nephropathy

–Initial dilated comprehensive eye exam within 5 years of diagnosis and then annually

–Monofilament testing with pinprick, temperature and vibration sensation for screening of peripheral neuropathy 5 years after diagnosis and then annually

–Annual influenza vaccine in patients ≥6 months of age

–Pneumococcal polysaccharide vaccine to all patients ≥2 years

–Hepatitis B vaccination to unvaccinated adults aged 19 to 59 years

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DIET

American Diabetic Association diet: http://www.diabetes.org/food-and- fitness/food/

Carbohydrate counting using insulin-to-carbohydrate ratio with all meals and snacks allows patient flexibility in eating.

PROGNOSIS

Initial remission or honeymoon phase with decreased insulin needs and easier control, usually 3 to 6 months

Current prognosis for reduced life expectancy:

–Increasing longevity and quality of life with careful blood glucose monitoring, improvement in insulin delivery regimens, and appropriate glycemic control

COMPLICATIONS

Microvascular disease (retinopathy, nephropathy, neuropathy)

Hyperlipidemia

Macrovascular disease (coronary and cerebral artery disease)

Chronic foot ulcers/amputations

Hypoglycemia

DKA

Excessive weight gain

Increased risk for preeclampsia and preterm delivery

Driving mishaps

Psychological problems of chronic disease

REFERENCES

1.American Diabetes Association. Standards of medical care in diabetes— 2016: summary of revisions. Diabetes Care. 2016;39(Suppl 1):S4–S104.

2.Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet. 2014;383(9911):69–82.

3.Stankov K, Benc D, Draskovic D. Genetic and epigenetic factors in etiology of diabetes mellitus type 1. Pediatrics. 2013;132(6):1112–1122.

4.Silverstein J, Klingensmith G, Copeland K, et al. Care of children and adolescents with type 1 diabetes: a statement of the American Diabetes Association. Diabetes Care. 2005;28(1):186–212.

5.Mooradian AD, Bernbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy. Ann Intern Med. 2006;145(2):125–134.

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6.Morgan E, Halliday SR, Campbell G, et al. Vaccinations and childhood type 1 diabetes mellitus: a meta-analysis of observational studies. Diabetologia. 2016;59(2):237–243.

SEE ALSO

Diabetes Mellitus, Type 2; Diabetic Ketoacidosis

CODES

ICD10

E10.9 Type 1 diabetes mellitus without complications

E10.8 Type 1 diabetes mellitus with unspecified complications E10.69 Type 1 diabetes mellitus with other specified complication

CLINICALPEARLS

Polyuria may present as nocturia, bedwetting, or incontinence in a previously continent child.

Young children are more likely to present in DKAbecause they may not express thirst or obtain fluids as readily as older children or adults.

Onset usually before the age of 19 years, but type 1 diabetes can present in patients who are well into their 30s.

Childhood vaccines have not shown to increase the risk of T1DM (6).

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DIABETES MELLITUS, TYPE 2

Swathi A.N. Rao, MD Sathya S. Krishnasamy, MD

Jeremy Golding, MD, FAAFP

BASICS

DESCRIPTION

Diabetes mellitus (DM) type 2 is due to a progressive insulin secretory defect in the setting of insulin resistance.

Geriatric Considerations

Monitor elderly for hypoglycemia; adjust doses for renal/hepatic dysfunction and cognitive function; less aggressive glucose targets than in younger patients

Pediatric Considerations

Incidence is increasing and parallels obesity epidemic.

Pregnancy Considerations

Diet, metformin, glyburide, and insulin are all options for treatment of gestational diabetes.

EPIDEMIOLOGY

Incidence

1.5 million new cases in 2015

Prevalence

Estimated 23.1 million Americans (7.4% of the population); 90–95% are likely type 2.

Higher education associated with lower prevalence

ETIOLOGYAND PATHOPHYSIOLOGY

Peripheral insulin resistance and/or defective insulin secretion with increased hepatic gluconeogenesis

Genetic factors: monogenic (e.g., PPARγ and insulin gene mutations) and polygenic

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Obesity (body mass index [BMI] ≥25 kg/m2) and visceral adiposity

Gut microbiome changes

Drugor chemical-induced (e.g., glucocorticoids, highly active antiretroviral therapy [HAART], atypical antipsychotics, organ transplant immunosuppressants)

Genetics

Genome-wide association studies in progress to identify associated genes; 50% concordance in monozygotic twins

Family history is strongly predictive of risk.

RISK FACTORS

Gestational diabetes or history of baby with birth weight ≥4 kg (9 lb)

Polycystic ovary syndrome (PCOS)

Hypertriglyceridemia or low high-density lipoprotein (HDL)—marker for insulin resistance

Ethnicity: African American, Latino, Native American, Asian, and Pacific Islander

Sedentary lifestyle

Use of thiazides, antipsychotics, glucocorticoids, and statins

GENERALPREVENTION

Maintenance of normal weight, or weight loss of 7% body weight, exercise 150 min/week, and decrease in carbohydrates and overall caloric intake. Moderate-intensity exercise and resistance training are recommended.

Higher intake of nuts, coffee, tea, and yogurt (1)[A]

Use of metformin and thiazolidinediones (TZDs) in select patients with prediabetes (1)[A].

COMMONLYASSOCIATED CONDITIONS

Hypertension, dyslipidemia, metabolic syndrome, fatty liver disease, infertility, PCOS, acanthosis nigricans, hemochromatosis

DIAGNOSIS

HISTORY

Polyuria, polydipsia, polyphagia, weight loss, weakness, fatigue, blurry vision,

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