Diabetes mellitus (DM) comprises a group of metabolic disorders that share the common feature of hyperglycemia. DM is currently classified on the basis of the pathogenic process that leads to hyperglycemia. Type 1 DM is characterized by insulin deficiency and a tendency to develop ketosis-it is most commonly caused by autoimmune destruction of the pancreatic islet beta cells. Type 2 DM is a heterogeneous group of disorders characterized by variable degrees of insulin resistance, impaired insulin secretion, and excessive hepatic glucose production-it is strongly associated with obesity. Other specific types include DM caused by genetic defects (maturity-onset diabetes of the young [MODY] and other rare monogenic disorders), diseases of the exocrine pancreas (chronic pancreatitis, cystic fibrosis, hemochromatosis), endocrinopathies (acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, hyperthyroidism), drugs (nicotinic acid, glucocorticoids, thiazides, protease inhibitors), and pregnancy (gestational DM). The phenotype of these monogenetic and secondary types of DM typically resembles type 2 DM; its severity depends on the degree of beta cell dysfunction and prevailing insulin resistance.
The worldwide prevalence of DM is increasing rapidly; type 2 DM frequency in particular is rising in parallel with the epidemic of obesity (Chap. 175 Obesity). In the past two decades, the worldwide prevalence of DM has increased more than 10-fold, from as estimated 30 million to >400 million cases. In the United States, the adult prevalence of DM ranges from 7-11% of the population, increasing with age. A significant portion of persons with DM are undiagnosed.
DM is attended by serious morbidity and significant mortality; it is consistently a leading cause of death worldwide.
Criteria for the diagnosis of DM are summarized in Table 176-1 Criteria for the Diagnosis of Diabetes Mellitus.
Screening with a fasting plasma glucose level or HbA1c is recommended every 3 years for individuals aged ≥45, as well as for younger individuals who are overweight (body mass index ≥25 kg/m2 ) and have one or more additional risk factors (Table 176-2 Risk Factors for Type 2 Diabetes Mellitus).
The metabolic syndrome (also known as insulin resistance syndrome or syndrome X) is a term used to describe a commonly found constellation of metabolic derangements that includes insulin resistance (with or without diabetes), hypertension, dyslipidemia, central or visceral obesity, and endothelial dysfunction and is associated with accelerated cardiovascular disease (Chap. 120 Metabolic Syndrome).
Common presenting symptoms of DM include polyuria, polydipsia, weight loss, fatigue, weakness, blurred vision, frequent superficial infections, and poor wound healing. In early type 2 DM, symptoms may be more subtle and consist of fatigue, poor wound healing, and paresthesias. The lack of symptoms is the main reason for the delayed diagnosis of type 2 DM. Many pts are diagnosed based on screening or during blood tests taken for other reasons. A complete medical history should be obtained with special emphasis on weight, exercise, smoking, ethanol use, family history of DM, and risk factors for cardiovascular disease. In a pt with established DM, assessment of prior diabetes care, HbA1c levels, self-monitoring blood glucose results, frequency of hypoglycemia, and pt's knowledge about DM should be obtained. Special attention should be given on physical examination to retinal examination, bp, foot examination (including vibratory sensation and monofilament testing), peripheral pulses, and insulin injection sites. Acute complications of DM that may be seen on presentation include diabetic ketoacidosis (DKA) (type 1 DM) and hyperglycemic hyperosmolar state (type 2 DM) (Chap. 25 Diabetic Ketoacidosis and Hyperosmolar Coma).
The chronic complications of DM are listed below:
- Ophthalmologic: nonproliferative or proliferative diabetic retinopathy, macular edema, rubeosis of iris, glaucoma, cataracts
- Renal: proteinuria, end-stage renal disease (ESRD), type IV renal tubular acidosis
- Neurologic: distal symmetric polyneuropathy, polyradiculopathy, mononeuropathy, autonomic neuropathy
- Gastrointestinal: fatty liver, gastroparesis, diarrhea, constipation
- Genitourinary: cystopathy, erectile dysfunction, female sexual dysfunction, vaginal candidiasis
- Cardiovascular: coronary artery disease, congestive heart failure, peripheral vascular disease, stroke
- Lower extremity: foot deformity (hammer toe, claw toe, Charcot foot), ulceration, amputation
- Dermatologic: Infections (folliculitis, furunculosis, cellulitis), necrobiosis, poor healing, ulcers, gangrene
- Dental: Periodontal disease
| TREATMENT | ||
Diabetes MellitusOptimal treatment of DM requires more than plasma glucose management. Comprehensive diabetes care should also detect and manage DM-specific complications and modify risk factors for DM-associated diseases. The pt with type 1 or type 2 DM should receive education about nutrition, exercise, care of diabetes during illness, and medications to lower the plasma glucose. In general, the target HbA1c level should be <7.0%, although individual considerations (age, ability to implement a complex treatment regimen, risk of hypoglycemia, and presence of other medical conditions) should also be taken into account. Intensive therapy reduces long-term complications but is associated with more frequent and more severe hypoglycemic episodes. Goal preprandial capillary plasma glucose levels should be 4.4-7.2 mmol/L (80-130 mg/dL) and postprandial levels should be <10.0 mmol/L (<180 mg/dL) 1-2 h after a meal. In general, pts with type 1 DM require 0.4-1.0 U/kg per day of insulin divided into multiple doses. Combinations of insulin preparations with different times of onset and duration of action should be used (Table 176-3 Properties of Insulin Preparationsa ). Preferred regimens include injection of long-acting insulin at bedtime with preprandial short-acting insulin (lispro, glulisine, or insulin aspart) or continuous SC insulin using an infusion device. Pramlintide, an injectable amylin analogue, can be used as adjunct therapy to control postprandial glucose excursions. Pts with type 2 DM may be managed with diet and exercise alone or in conjunction with oral glucose-lowering agents, insulin, or a combination of oral agents and insulin. The classes of oral glucose-lowering agents and dosing regimens are listed in Table 176-4 Agents Used for Treatment of Type 1 or Type 2 Diabetes. In addition, injectable glucagon-like peptide 1 (GLP-1, an incretin) analogues may be used in combination with metformin or sulfonylureas. A reasonable treatment algorithm for initial therapy proposes metformin as initial therapy because of its efficacy (1-2% decrease in HbA1c), known side-effect profile, and relatively low cost (Fig. 176-1. Glycemic Management of Type 2 Diabetes). Metformin has the advantage that it promotes mild weight loss, lowers insulin levels, improves the lipid profile slightly, lowers cancer risk, and does not cause hypoglycemia when used as monotherapy, although it is contraindicated in renal insufficiency, congestive heart failure, any form of acidosis, liver disease, or severe hypoxia, and should be temporarily discontinued in pts who are seriously ill or receiving radiographic contrast material. Metformin therapy can be followed by addition of a second oral agent (insulin secretagogue, DPP-IV inhibitor, thiazolidinedione, α-glucosidase inhibitor, or SLGT2 inhibitor). Combinations of two oral agents may be used with additive effects, with stepwise addition of bedtime insulin or a third oral agent if adequate control is not achieved. As endogenous insulin production falls, multiple injections of long-acting and short-acting insulin may be required, as in type 1 DM. Individuals who require >1 U/kg per day of long-acting insulin should be considered for combination therapy with an insulin-sensitizing agent such as metformin or a thiazolidinedione. Insulin-requiring type 2 DM pts may also benefit from addition of pramlintide. Based on demonstrations of a beneficial cardiovascular effect in certain individuals with type 2 DM and CVD, or at high risk of CVD, empagliflozin and liraglutide (and possibly canagliflozin) should now be considered in these populations. Bariatric surgery should be considered in selected pts (Chap. 175 Obesity). The morbidity and mortality of DM-related complications can be greatly reduced by timely and consistent surveillance procedures (Table 176-5 Guidelines for Ongoing, Comprehensive Medical Care for Pts with Diabetes). A routine urinalysis may be performed as an initial screen for diabetic nephropathy. If it is positive for protein, quantification of protein on a 24-h urine collection should be performed. If the urinalysis is negative for protein, a spot collection for albuminuria should be performed (present if 30-300 µg/mg creatinine on two of three tests within a 3- to 6-month period). A resting ECG should be performed in adults, with more extensive cardiac testing for high-risk pts. Therapeutic goals to prevent complications of DM include management of proteinuria with ACE inhibitor or angiotensin receptor blocker therapy, bp control (<140/90 mmHg, and <130/80 in individuals with CVD or chronic kidney disease), and dyslipidemia management (LDL <2.6 mmol/L [<100 mg/dL], HDL >1.1 mmol/L [>40 mg/dL] in men and >1.38 mmol/L [50 mg/dL] in women, triglycerides <1.7 mmol/L [<150 mg/dL]). In addition, any diabetic pt >40 years should take a statin, regardless of the LDL cholesterol, and in those with existing cardiovascular disease, the LDL target should be <1.8 mmol/L (70 mg/dL). If LDL cholesterol remains elevated despite statin therapy in a high risk, consider addition of ezetimibe or PCSDK9 inhibitor. MANAGEMENT OF THE HOSPITALIZED PTThe goals of diabetes management during hospitalization are near-normal glycemic control, avoidance of hypoglycemia, and transition back to the outpatient diabetes treatment regimen. Pts with type 1 DM undergoing general anesthesia and surgery, or with serious illness, should receive continuous insulin, either through an IV insulin infusion or by SC administration of a reduced dose of long-acting insulin. Short-acting insulin alone is insufficient to prevent the onset of diabetic ketoacidosis. Oral hypoglycemic agents should be discontinued in most pts with type 2 DM at the time of hospitalization. Either regular insulin infusion (0.05-0.15 U/kg per hour) or a reduced dose (by 30-50%) of long-acting insulin and short-acting insulin (held, or reduced by 30-50%), with infusion of a solution of 5% dextrose, should be administered when pts are NPO for a procedure. A regimen of long- and short-acting SC insulin should be used in type 2 pts who are eating. The glycemic goal for hospitalized pts with DM should be a preprandial glucose of <7.8 mmol/L (<140 mg/dL) and <10 mmol/L (<180 mg/dL) at post-meal times. For critically ill pts, glucose levels of 7.8-10.0 mmol/L (140-180 mg/dL) are recommended. Those with DM undergoing radiographic procedures with contrast dye should be well hydrated before and after dye exposure, and the serum creatinine should be monitored after the procedure. |