Diabetes Mellitus

DIAGNOSTIC SUMMARY

— Fasting (overnight): venous plasma glucose ≥126 mg/dL on at least two separate occasions

— After ingestion of 75 g glucose: venous plasma glucose ≥200 mg/dL at 2 hours postingestion and at least one other sample during 2-hour test

— Random blood glucose of 200 mg/dL or more plus presence of suggestive symptoms

• Classic symptoms: polyuria, polydipsia, polyphagia

• Presenting symptoms: fatigue, blurred vision, poor wound healing, periodontal disease, frequent infections

GENERAL CONSIDERATIONS

Diabetes is a chronic disorder of carbohydrate, fat, and protein metabolism characterized by fasting elevations of blood glucose and greatly increased risk of heart disease, stroke, kidney disease, retinopathy, and neuropathy. Causes: the pancreas does not secrete enough insulin, or cells of body become resistant to insulin. Sugar cannot enter muscle or fat cells, causing serious complications. More than 18.5 million Americans have diabetes, but one third do not know this or ever consult a physician.

Major complications of diabetes: cardiovascular disease, hypertension, retinopathy, renal disease, neuropathy, amputations, periodontal disease, pain (arthritis, neuropathy, circulatory insufficiency, muscle pain [fibromyalgia]), depression (even years before dia-betes diagnosis), autoimmune disorders (e.g., thyroid disease, arthritis)

Classification

Two major categories:

• Type 1 (insulin-dependent diabetes mellitus [IDDM]): most often in children and adolescents (juvenile-onset diabetes).

• Type 2 (non-insulin-dependent diabetes mellitus [NIDDM]): onset after age 40 years (adult-onset diabetes). Incidence of this type is rising in sedentary, obese children. Fifteen percent of adults diagnosed with type 2 actually have type 1.

Features	Type 1	Type 2
Age at onset	Usually <40 years	Usually >40 years
Percentage of all diabetics	<10%	>90%
Seasonal trend	Fall and winter	None
Family history	Uncommon	Common
Appearance of symptoms	Rapid	Slow
Obesity at onset	Uncommon	Common
Insulin levels	Decreased	Variable
Insulin resistance	Occasional	Often
Treatment with insulin	Always	Not required
Beta-cells	Decreased	Variable
Ketoacidosis	Frequent	Rare
Complications	Frequent	Frequent

• IDDM (type 1): complete destruction of pancreas beta-cells, which manufacture insulin. Patients require lifelong insulin supplementation and must manage blood sugar daily by modifying insulin types and dosage schedules according to results of regular blood sugar testing. Ten percent of diabetics are type 1. Current causal theory focuses on injury to beta-cells plus a defect in tissue regeneration. Autoimmune component is revealed by antibodies to beta-cells present in 75% of cases compared with 0.5%-2.0% of normals. Antibodies to beta-cells may develop in response to cell destruction from other mechanisms (chemical, free radical, viral, food allergy).

• NIDDM (type 2): affects 90% of diabetics. Insulin is elevated because of a loss of sensitivity to insulin by cells of body. Obesity is the major contributor; 90% of type 2 diabetics are obese. Achieving ideal body weight is linked to restoring normal blood sugar in most cases. Diet is of primary importance, implemented diligently before drug use. Most type 2 diabetics can be controlled by diet alone.

• Other types of diabetes:

— Secondary diabetes: a result of conditions or syndromes (pancreatic disease, hormone disturbances, drugs, malnutrition)

— Gestational diabetes: glucose intolerance during pregnancy

— Impaired glucose tolerance: includes prediabetic, chemical, latent, borderline, subclinical, and asymptomatic diabetes

Individuals with impaired glucose tolerance have blood glucose and glucose tolerance test results intermediate between normal and clearly abnormal. Reactive hypoglycemia may be a prediabetic condition.

Prediabetes and Syndrome X

Prediabetes (impaired glucose tolerance) entails abnormally high glucose. Although not high enough to fit the definition of NIDDM, it still needs to be treated. Many cases progress to type 2 DM. Impaired glucose tolerance is usually reversible, and DM is avoidable. High cholesterol, blood pressure, inflammation biomarkers, and blood clotting tendency are typical, increasing risk for cardiovascular disease, stroke, and so forth. Syndrome X is a cluster of abnormalities linked to refined carbohydrate consumption in the genetically predisposed. Syndrome X (metabolic cardiovas-cular risk syndrome [MCVS]), metabolic syndrome, Reaven’s syndrome, insulin resistance syndrome, atherothrombogenic syndrome) includes mild to moderately impaired glucose tolerance, hyperinsulinemia from insulin resistance, hypercholesterolemia, hypertriglyceridemia, hypertension, and abdominal obesity. Key factor is hyperinsulinemia caused by refined carbohydrates coupled with insulin resistance. Prediabetes, hypoglycemia, hyperinsulinemia, syndrome X, and type 2 DM are facets of the same disease and underlying dietary, lifestyle, and genetic causes.

DIAGNOSIS

In the patient with type 2 DM, classic symptoms are milder and often unnoticed. Fatigue, blurred vision, poor wound healing, periodontal disease, and frequent infections are presenting symptoms.

• Fasting blood glucose: taken after fasting at least 10 hours but not more than 16 hours. Normal fasting blood glucose is 70-99 mg/dL. Fasting blood glucose >126 mg/dL (7 mmol/L) on two separate occasions is diagnostic of diabetes. Fasting glucose ≥110 and <126 mg/dL indicates impaired glucose tolerance. Levels <50 mg/dL indicate fasting hypoglycemia.

• Postprandial glucose: 2 hours after meal. Level >200 mg/dL (11 mmol/L) indicates DM.

• Random glucose: anytime regardless of last meal. Level >200 mg/dL (11 mmol/L) indicates DM.

• Glucose tolerance test (GTT): gold standard because of its longstanding use but less reliable than fasting blood glucose if combined with hemoglobin A₁c (HgbA₁c).

Glucose Tolerance Test Response Criteria

• Normal: no level >160 mg/dL (9 mmol/L) and <150 mg/dL (8.3 mmol/L) at end of first hour; <120 mg/dL (6.6 mmol/L) at end of second hour.

• Flat: no variation >±20 mg/dL (1.1 mmol/L) from fasting value.

• Prediabetic: 140 mg/dL (7.8 mmol/L) to 180 mg/dL (10 mmol/L) at end of second hour.

• Diabetic: >180 mg/dL (10 mmol/L) during first hour; 200 mg/dL (11.1 mmol/L) or higher at end of first hour; 150 mg/dL (8.3 mmol/L) or higher at end of second hour.

• Glycosylated hemoglobin: proteins with attached glucose molecules (glycosylated peptides) are elevated severalfold in DM. Normal levels are 5%-7% of Hgb. Mild glucose elevations cause A₁c increase to 8%-10%; high glucose can increase A₁c to 20%. A₁c assay is a time-averaged indicator for preceding 2-4 months. It is simple and useful for assessing treatment efficacy and patient compliance. A₁c plus fasting glucose can diagnose DM but not as only criteria. A third of diabetics diagnosed with GTT have normal A₁c. Couple A₁c with fasting glucose and 2-hour postprandial glucose for a more accurate diagnosis. A₁c assay can determine relative glucose load and monitor therapy.

CAUSES OF DIABETES

MONITORING THE DIABETIC PATIENT

• Urine glucose monitoring: kidneys conserve glucose until blood glucose reaches 180 mg/dL (10 mmol/L). A negative urine glucose means blood glucose since previous voiding has been <180 mg/dL. Urine testing is crude; it gives no indication of blood glucose below 180 mg/dL. It is worthless for severe hypoglycemia or hyperglycemia.

• Urine ketone testing: when fat is the primary source of energy, ketones are produced. High ketone level spills over into urine. In the diabetic, ketonuria occurs with severe deficits in insulin availability or activity. Examples: a patient with IDDM accidentally or purposefully fails to take insulin; or a diabetic is ill, injured, or is given high doses of cortisone-related drugs. Loss of insulin effect impairs glucose uptake and use of glucose. The result is hyperglycemia, fat burning for energy, and toxemia from acidic ketones, with severe dehydration from water loss caused by glycosuria. This state is the deadly medical emergency termed “diabetic ketoacidosis,” necessitating intravenous (IV) insulin, IV fluids, and intensive care unit monitoring. Urine ketone testing is critical, especially in IDDM. Urine ketones (with hyperglycemia) may indicate impending or established ketoacidosis, requiring immediate intervention. Advise patients to test urine for ketones during acute illness; during severe stress, when blood glucose is consistently elevated (>300 mg/dL [16.7 mmol/L]), regularly during pregnancy; or in the presence of symptoms of ketoacidosis (nausea, vomiting, abdominal pain).

• Self-monitoring of blood glucose: glycemic control is the most important factor in the long-term risk of serious complications in type 1 and type 2 DM. Self-monitoring of blood glucose allows the patient to modify treatment to maintain glycemic control, detect hypoglycemia, adjust care to daily circumstances (food intake, exercise, stress, illness), detect and treat severe hyperglycemia, increase therapeutic compliance, and improve motivation from immediate feedback.

• Optimal schedule for self-monitoring of blood glucose

— Awakening and just before each meal. Ideal before meals is <120 mg/dL (6.7 mmol/L).

Optimal Range for Self-Monitored Blood Glucose ^*

Fasting or before meals	80-110 mg/dL (4.4-6.7 mmol/L)
Two hours after eating (postprandial)	<140 mg/dL (7.8 mmol/L)
At bedtime	100-140 mg/dL (5.6-7.8 mmol/L)