Diabetes Type 1

Definition
Chronic disease caused by pancreatic insufficiency (deficiency) of insulin production
Results in hyperglycemia and end-organ complications (e.g., accelerated atherosclerosis, neuropathy, nephropathy, and retinopathy)


Epidemiology
Mean age of onset 8–12 years, peaking in adolescence
Onset 1.5 years earlier in girls than boys
Rapid decline in incidence after adolescence
15/100,000 per year
Racial predilection for whites
African Americans have lowest overall incidence.
More prevalent in children; true type 1 diabetes can occur in nonpediatric patients who are well into their 30s
Over the past 10 years, a larger percentage of young children (<5 years) present with diabetes.

Risk Factors
Certain human leukocyte antigen (HLA) types
Presence of a specific 64,000 mw protein that may be responsible for antibody formation
Family history
Dietary factors: Breast-feeding may provide a degree of protection against the disease, whereas diets high in dairy products are associated with an increased risk of the disease.
Insulin-dependent or non–insulin-dependent diabetes in any 1st-degree relatives
Slightly greater risk for a child if the father has type 1 diabetes

Genetics
Mode of genetic expression not clear
Genes located on major histocompatibility complex on chromosome 6
HLA DR3 and DR4 are individually associated with an increased risk; if a person is carrying both susceptibility genes, the relative risk is increased.
HLA B8 and B15 associated with increased risk

Pathophysiology
Alteration in immunologic integrity, placing the β cell at special risk for inflammatory damage
The mechanism of damage is autoimmune.

Aetiology
Inherited defect
Associated environmental factors:

• Viruses (such as mumps, coxsackie, cytomegalovirus, and hepatitis viruses)
• Diet high in nitrosamines
• Environmental toxins

Emotional and physical stress
Commonly Associated Conditions
Autoimmune diseases, such as hypothyroidism and Addison disease:

• Screening regularly for hypothyroidism is particularly important in females.

Diabetes mellitus can also be seen as part of multiple endocrine adenomatosis.

Diagnosis

History	Polyuria and polydipsia Polyphagia is classic, but not common Anorexia is commonly observed. Weight loss 10–30%:- Often almost devoid of body fat at diagnosis Increased fatigue, lethargy Muscle cramps Irritability and emotional lability Vision changes, such as blurriness Altered school and work performance Headaches Anxiety attacks Abdominal discomfort, nausea
Blood glucose	Fasting glucose >126 mg/dL (7.0 mmol/L) or random of >200 mg/dL (11.1 mmol/L) HbA1c level >6.5% - a diagnostic criterion for diabetes
Investigate for secondary diabetes	Pancreatic disease (pancreatitis, cystic fibrosis) Hormonal disorders (pheochromocytoma, multiple endocrine adenomatosis) Inborn errors of metabolism (glycogen storage disease, type 1) Genetic disorders with insulin resistance (acanthosis nigricans) Hereditary neuromuscular disease Progeroid syndromes Obesity (Prader-Willi syndrome) Cytogenetic syndromes (trisomy 21, Klinefelter, and Turner syndromes) Drug- or chemical-induced glucose intolerance
Others	Consider human leukocyte antigen (HLA) typing Blood glucose Electrolytes Venous pH Urinalysis; check glucose and ketones FBC- white blood cell may be elevated Hemoglobin A1c level C-peptide insulin level Islet-cell antibodies T4 and thyroid antibodies Glutamic acid decarboxylase (GAD-65) antibodies
Celiac disease scrrening	Celiac disease, screen tissue transglutaminase (tTG) or endomysial (EMA) antibodies

Differential Diagnosis
Benign renal glycosuria
Glucose intolerance
Type 2 non–insulin-dependent diabetes:

Children might have maturity-onset diabetes of the young (MODY)Acute poisonings (salicylate poisoning can cause hyperglycemia and glycosuria, and may mimic diabetic ketoacidosis)

Management

Normoglycemia (adjusted for age): Strive for blood glucose levels in range of 80–150 mg/dL (4.4–8.3 mmol/L) all the time (80–120 in older patients)
Very tight control might be dangerous in young children due to risk of repeated hypoglycemia.
Hemoglobin A1c target levels:

• Children <6 years: 7.5–8.5%
• Children 6–12 years: <8.0%
• Adolescents 13–19: <7.5% (<7.0% if achieved without excessive hypoglycemia)
• Nonpediatric patients: <6.0%

Insulin (first line)	Source: DNA-recombinant human insulin is the main source of insulin in recent years Types: Lantus (insulin glargine), Humalog, NovoLog, NPH (infrequently used), regular, premixtures of 70/30 and 75/25 (these mixtures are not commonly used in children) Newer insulins include Levemir (similar to Lantus) and Symlin (short-acting insulin) Lantus (glargine insulin) SQ once or twice daily. Lantus insulin is an almost 24-hour, nearly peakless insulin, which essentially provides basal insulin throughout the day. Humalog or NovoLog insulin SQ before meals and snacks. Dosage based on an insulin-to-carbohydrate ratio (e.g., 1:10, meaning 1 unit of insulin for every 10 g of carbohydrate eaten; PLUS correction factor (e.g., BS-100/50, meaning if the blood glucose is >150, or a level determined by their doctor, subtract 100 from the BG level, and divide that number by 50—this a supplement to the ratio if the blood glucose is elevated). Insulin pump (external) therapy: Insulin pump therapy in many centers has even replaced SQ insulin as 1st-line treatment. Used much more commonly in diabetic children and quite commonly in nonpediatric patients; basal insulin is given continuously (rates preset). Bolus doses are given before meals and snacks, based on insulin-to-carbohydrate ratios as above; all insulin is Humalog or NovoLog.
Metformin	Oral hypoglycemics not indicated in type 1 diabetes (unless an obese patient, who may have MODY; or a combination of type 1 and type 2)
Immunosuppressants:	Cyclosporine (used infrequently): Reduces rate of autoimmune β-cell destruction; must be started in initial weeks after diagnosis Studies show that at 1 year, 20% of cyclosporine-treated patients on no insulin, compared to 12–15% of placebo controls; after 1 year, progressive decline in β-cell function and loss of remission.
Prevent acute complications	Hypoglycemic insulin reactions Ketoacidosis
Follow-up	Normal; full participation in sports activities Regular aerobic exercise is preferable. Patient Monitoring Blood pressure (BP) monitoring at every office visit Monitor height, weight, and sexual maturation (in children). Daily home blood glucose monitoring with home blood glucose meter: Blood tests should be done at least 4–6 times daily (more frequently in pump patients) for optimal monitoring.
Annual screening	After 5 years of diabetes, sooner if glycemic control is suboptimal): Microalbuminuria for earliest signs of possible nephropathy If elevated, depending on level, even if BP is normal, consider an angiotensin-converting enzyme (ACE) inhibitor (such as Vasotec [Enalapril]) Ophthalmology exam (after 3–5 years of diabetes, also depending on glycemic control); regularly thereafter Cardiology evaluation as needed Yearly lipid profile, thyroid levels, blood chemistries, FBC Annual influenza vaccine

Complications
Microvascular disease (retinopathy, nephropathy, neuropathy)

Hyperlipidemia

Macrovascular disease (coronary and cerebral artery disease)

Chronic foot ulcers/amputations

Hypoglycemia

Diabetic ketoacidosis

Excessive weight gain

Psychologic problems of chronic disease

Prognosis
Increasing longevity and quality of life with careful blood glucose monitoring and improvement in insulin delivery regimens

At this time, reduced life expectancy, but has improved greatly over the past 20 years