Diabetes Mellitus, Type 1

Essentials of Diagnosis

• Polyuria, polydipsia, and weight loss associated with random plasma glucose ≥ 200 mg/dL (11.1 mmol/L)

• Plasma glucose ≥ 126 mg/dL (7.0 mmol/L) after an overnight fast, documented on more than one occasion

• Ketonemia, ketonuria, or both

General Considerations

• Caused by pancreatic islet B-cell destruction

• Destruction autoimmune in > 95% of cases (type 1a) and idiopathic in the remainder (type 1b)

• About 95% of type 1 patients possess either HLA-DR3 or HLA-DR4 compared with 45–50% of white controls. HLA-DQB1*0302 is an even more specific marker for susceptibility

• Most patients have circulating antibodies to islet cells (ICA), glutamic acid decarboxylase (GAD65), insulin (IAA), and tyrosine phosphatase IA2 (ICA-512) and zinc transporter 8 (ZnT8) at diagnosis

• The rate of pancreatic B-cell destruction ranges from rapid to slow

• Prone to ketoacidosis

• Plasma glucagon is elevated

• C peptide levels do not reliably distinguish between type 1 and type 2 diabetes mellitus

Demographics

• Occurs at any age but most commonly arises in children and young adults with a peak incidence at age 10–14 years

• Incidence

  • Highest in Scandinavia

  • In Finland, yearly incidence in children 14 years old or younger is 40 per 100,000

  • Lowest incidence is < 1 per 100,000 per year in China and parts of South America

  • In the United States, average is 16 per 100,000

  • Incidences are higher in states densely populated with persons of Scandinavian descent such as Minnesota

  • The global incidence is increasing, with an annual increase of ~3%

• An estimated 34.2 million people (10.5%) in the United States have diabetes mellitus, of which approximately 5–10% have type 1 diabetes

Symptoms and Signs

• Increased thirst (polydipsia)

• Increased urination (polyuria)

• Increased appetite (polyphagia) with weight loss

• Ketoacidosis

• Paresthesias

• Recurrent blurred vision

• Vulvovaginitis or pruritus

• Nocturnal enuresis

• Postural hypotension from lowered plasma volume

Differential Diagnosis

• Type 2 diabetes

• Hyperglycemia resulting from other causes

  • Medications (high-dose corticosteroids, pentamidine)

  • Other endocrine conditions (Cushing syndrome, glucagonoma, acromegaly, pheochromocytoma)

• Metabolic acidosis of other causes (alcoholic ketoacidosis)

• Nondiabetic glycosuria (renal glycosuria)

Laboratory Tests

• Fasting plasma glucose > 126 mg/dL (7 mmol/L) or > 200 mg/dL (11.1 mmol/L) 2 h after glucose load (Table 27–4)

• Hemoglobin A_1c (HbA_1c) of at least 6.5%

• Ketonemia, ketonuria, or both

• Urine glucose (Clinistix, Diastix)

• Urine and blood ketones (Acetest, Ketostix)

• Hemoglobin A_1c reflects glycemic control over preceding 8–12 weeks

• Serum fructosamine

  • Reflects glycemic control over preceding 2 weeks

  • Helpful in presence of abnormal hemoglobins or in ascertaining glycemic control at time of conception among diabetic women

• Lipoprotein abnormalities; unlike in type 2 diabetes, moderately deficient control of hyperglycemia in type 1 diabetes is associated with only slight elevation of low-density lipoprotein (LDL) cholesterol and serum triglycerides and minimal change in high-density lipoprotein (HDL) cholesterol

Medications

• Tables 27–6, 27–7, 27–8

• Regular insulin (a U500 concentration is available for use in patients who are very resistant)

• Rapidly-acting insulin analogs: insulin lispro, insulin aspart, insulin glulisine

• Intermediate-acting insulin purified: Neutral protamine Hagedorn (NPH)

• Premixed insulins

  • 70% NPH/30% regular (70/30 insulin)

  • 50% NPH/50% regular (50/50 insulin)

  • 70% neutral protamine lispro (NPL)/25% insulin lispro (Humalog Mix 75/25)

  • 50% NPL/50% insulin lispro (Humalog Mix 50/50)

  • 70% insulin aspart protamine/30% insulin aspart (Novolog Mix 70/30)

• Long-acting insulins purified: insulin glargine, insulin detemir

• Pramlintide (islet amyloid polypeptide analog)

Surgery

• Infuse intraoperatively and in immediate postoperative period: D5 0.9% saline with 20 mEq KCl intravenously at 100–200 mL/h. Infuse regular human insulin (25 units/250 mL 0.9% saline) into intravenous tubing at 1–3 units/h

• Monitor blood glucose hourly and adjust infusion for target glucose levels 100–180 mg/dL

• Patients receiving simultaneous pancreas and kidney transplants have 83% chance of pancreatic graft survival at 1 year and 69% at 5 years

• Solitary pancreas transplant only for recurrent life-threatening metabolic instability

• Pancreas transplant alone graft survival is 78% at 1 year and 54% at 5 years

• Islet cell transplantation

  • Insulin independence for more than 5 years has been demonstrated in patients who got anti-CD3 antibody or anti-thymocyte globulin induction immunosuppression and calcineurin inhibitors, mTor inhibitors, and mycophenolate mofetil as maintenance immunosuppression

  • Long-term immunosuppression is necessary to prevent allograft rejection and to suppress the autoimmune process that led to the disease initially

  • One major limitation is the need for more than one islet infusion to achieve insulin independence

Therapeutic Procedures

• Eucaloric healthy diet

• Limitations

  • Saturated fats should be limited to < 10% of daily calories

  • Dietary cholesterol intake should be < 300 mg/day

  • For those patients with kidney disease, dietary protein should be maintained at the recommended daily allowance of 0.8g/kg/day

• Treat microalbuminuria with angiotensin-converting enzyme (ACE) inhibitor to retard diabetic nephropathy

• Treat hypertension and hyperlipidemia (reduce LDL to < 100 mg/dL)

• Attempts have been made to prolong the partial clinical remission ("honeymoon") using such drugs as cyclosporine, azathioprine, prednisone, and antithymocyte globulin

Follow-Up

• Patients who received intensive insulin (multiple-injection or pump) therapy to obtain a mean HbA_1c of 7.2% (normal: < 6%), experienced a 60% reduction in risk of diabetic retinopathy, nephropathy, and neuropathy, compared with patients who received conventional therapy

Complications

• Diabetic ketoacidosis

• Hypoglycemia and altered awareness of hypoglycemia

• Diabetic retinopathy, cataracts

• Nephropathy

• Neuropathy

• Diabetic atherothrombosis (heart disease, peripheral vascular disease)

• Lipodystrophy at injection sites

• Diabetic cheiroarthropathy

• Adhesive capsulitis

• Carpal tunnel syndrome

• Dupuytren contractures

Prognosis

• The Diabetes Control and Complications Trial (DCCT) showed that the poor prognosis for 40% of patients with type 1 diabetes is markedly improved by optimal care

• Patients can have a full life

• Tight control (mean HbA_1c 7.2%, normal: < 6%) in the DCCT was associated with a threefold greater risk of serious hypoglycemia as well as greater weight gain. However, no deaths occurred because of hypoglycemia, and no evidence of posthypoglycemic cognitive damage was detected

• Subsequent end-stage kidney disease predicted by microalbuminuria > 30 mcg/ mg creatinine; risk decreased by treatment with ACE inhibitor

Prevention

• Acetylsalicylic acid (aspirin) 81–325 mg (enteric coated) orally daily to reduce risk of diabetic atherothrombosis without increasing risk of gastrointestinal hemorrhage

• Instruction in personal hygiene, in particular, care of feet, skin, and teeth

• Yearly diabetic eye examination

• Patient self-management training

• Self-monitoring of blood glucose

• Exercise

When to Refer

• Team educational approach is critical. Enlist nutritionist

• Poorly controlled diabetes

When to Admit

• Altered mental status

• Diabetic ketoacidosis

• Marked volume disorders

• Marked electrolyte disorders

• Unstable comorbid conditions