Diabetes Mellitus

Diabetes Mellitus

Objectives

The student will be able to diagnose, classify, and manage diabetes mellitus in a clinic setting.

Classifications

Type 1 Diabetes

associated with b-cell destruction, usually leading to absolute insulin deficiency.
previously called insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes.
ketosis-prone, associated with certain HLA antigens and islet cell antibodies.
10% of diabetics in the United States are Type 1.

Type 2 Diabetes

ranges from predominantly insulin resistant with relative insulin deficiency to predominantly an insulin secretory defect with insulin resistance.

previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes.

autosomal dominant inheritance pattern is present.

80% to 90% of these patients are obese.

90% of diabetics in the United States are Type 2.

Table 1. Diagnosing Diabetes
TEST
STAGE	Fasting Plasma Glucose (FPG)(Preferred)*	Casual Plasma Glucose	Oral Glucose Tolerance Test (OGTT)
Diabetes	FPG 126 mg/dL (7.0 mmol/L)**	Casual plasma glucose 200 mg/dL (11.1 mmol/L) plus symptoms***	Two-hour plasma glucose (2hPG) 200 mg/dL****
Impaired Glucose Homeostasis	Impaired fasting glucose (IFG) = FPG 110 and < 126 g/dL		Impaired glucose tolerance (IGT) = 2hPG > 140 and < 200 mg/dL
Normal	FPG < 110 mg/dL		2hPG < 140 mg/dL

* The FPG is the preferred test for diagnosis, but any 1 of the 3 listed is acceptable. In the absence of unequivocal hyperglycemia with acute metabolic decompensation, 1 of these 3 tests should be used on a different day to confirm diagnosis.
** Fasting is defined as no caloric intake for at least 8 hours.
*** Casual = any time of day without regard to time since last meal; symptoms are the classic ones of polyuria, polydipsia, and unexplained weight loss.
**** OGTT should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. The OGTT is not recommended for routine clinical use.

From: Rayburn WE. Clinical perspectives: Diagnosis and classification of diabetes mellitus: Highlights from the American Diabetes Association. J Reprod Med 0024-7758/97/4209-0585.

Table 2. Criteria for Testing in Asymptomatic Undiagnosed Individuals

Type 1 Diabetes: Testing presumably healthy individuals for the presence of any immune markers, outside of a clinical trials setting, is not recommended.

Type 2 Diabetes: In asymptomatic, undiagnosed individuals, testing for diabetes should be considered in all individuals at age 45 and above, and, if normal, it should be repeated at 3-year intervals.

Testing should be considered at a younger age, or be carried out more frequently, in individuals who:

are obese [ 120% desirable body weight or a body mass index (BMI) 27 kg/m²]
have a first-degree relative with diabetes are members of a high-risk ethnic population (African American, Hispanic, Native American, Asian)
delivered a baby weighing >9 lbs or were diagnosed with GDM
are hypertensive ( 140/90 mm Hg)
have an HDL cholesterol level 35 mg/dL and/or a triglyceride level 250 mg/dL
on previous testing, had IGT or IFG.
The FPG is the preferred diagnostic test because of its ease of administration, convenience, acceptability to patients, and lower cost.

(adapted from Diabetes Care, July 1997;20(7): 11.)

Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG)

Patients with IGT respond abnormally to the glucose tolerance test, but do not meet the criteria required to diagnose diabetes.

Patients with IFG have abnormal fasting glucose, but are not diagnostic for D.M. and have normal glucose tolerance tests.

IGT and IFG are not clinical entities, but are risk factors for future D.M. and cardiovascular disease.

Diagnostic Criteria and Screening

(refer to Tables 1 and 2)

HbA_1c measurement is not currently recommended for diagnosis of D.M.

Outpatient Management

Goals of Therapy

Prevention and early treatment of acute complications, which include diabetic ketoacidosis, hyperosmolar state, and infections, especially urinary tract, skin, and foot infections.
Prevention of long-term complications. There is strong evidence that tight control prevents renal or retinal complications. Peripheral neuropathy may be improved by better control of the blood glucose. Treatment goals must be tailored to the patient. Age and other factors influence risks and benefits.
Treatment is directed toward relieving symptoms, especially polyuria and polydipsia.

(refer to Table 3)

Methods of Therapy

Diet

The cornerstone of therapy for all obese diabetics is a weight-reduction diet. This is especially true of the obese Type 2 diabetic. The primary emphasis is a reduction in total calories in order to effect a weight loss. This often requires a diet limiting daily intake to 1200 calories or less. Even a relatively small amount of weight loss usually achieves control (85% of patients), and continued, gradual weight loss will maintain control in the obese, Type 2 diabetic. Without weight loss in these patients, good control of the diabetes is very difficult to achieve.

The type of calories and timing of the meals is more important in the non-obese diabetic on insulin.

Increased fiber content may be of benefit.

A dietitian should be consulted for instruction and on-going supervision of the diabetic patient.

Exercise

Adequate physical activity has been shown to increase insulin receptor sites and lower insulin requirements. A regular exercise program should be prescribed.

Table 3. Glycemic Control for People with Diabetes*
Biochemical Index	Nondiabetic	Goal	Additional Action Suggested
Preprandial glucose (mg/dL)**	< 110	80-120	< 80 > 140
Bedtime glucose (mg/dL)**	< 120	100-140	< 100 > 160
HbA_1c (%)	< 6	< 7	> 8
* The values shown in this table are by necessity generalized to the entire population of individuals with diabetes. Patients with comorbid diseases, the very young and older adults, and others with unusual conditions or circumstances may warrant different treatment goals. These values are for nonpregnant adults. "Additional action suggested" depends on individual patient circumstances. Such actions may include enhanced diabetes self-management education, comanagement with a diabetes team, referral to an endocrinologist, change in pharmacological therapy, initiation of or increase in SMBG, or more frequent contact with the patient. HbA_1c is referenced to a nondiabetic range of 4.0-6.0% (mean 5.0%, SD 0.5%). ** Measurement of capillary blood glucose.

American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care, January 1998;21(Suppl. 1):S23-S31.

Oral Hypoglycemic Agents

Sulfonylureas may be used in Type 2 diabetics over 30 who have failed diet therapy, or as an adjunct while diet and exercise are being instituted. They are more likely to be effective in patients with mildly elevated glucose (FBS <300).

The second generation agents glyburide and glipizide are more potent and may be attempted in patients with marked hyperglycemia or who failed the first generation agents.

Sulfonylureas cannot be used during pregnancy and are contraindicated in patients with hepatic or renal dysfunction. Because of its long duration of action, glyburide should be avoided in elderly patients.

Metformin (Glucophage) is a new oral hypoglycemic agent that may be
used alone or in combination with a sulfonylurea agent. Combination therapy may delay or avoid insulin therapy when treatment with one oral agent has failed. Metformin is contraindicated in patients with renal dysfunction (serum creatinine 1.5 in men and 1.4 in women). Also avoid metformin in patients who have a history of binge drinking and those prone to dehydration.

Troglitazone (Rezulin) improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. It can be used as monotherapy or in combination with other oral agents or insulin. It has synergistic effects with sulfonylureas. When added to insulin, the dose of insulin can usually be lowered approximately 50%. Disadvantages include high cost and potential hepatic injury. Monitoring LFTs is required.

Table 4. Sulfonylureas*
Drug	Tablet Size	Daily Dose	Duration of Action
Tolbutamide (Orinase)	250 mg and500 mg	0.5-2 g in 2 or 3 divided doses	6-12 hours
Tolazamide(Tolinase)	100 mg, 250 mg, and 500 mg	0.1-l g as single dose or in 3 divided doses	Up to 24 hrs.
Glyburide (Diabeta, Micronase)	1.25 mg, 2.5 mg, and 5 mg doses	1.25-20 mg as single dose or in 2 divided	Up to 24 hrs.
Glipizide(Glucotrol)	5 mg and 10 mg	2.5-30 mg as single dose or in 2 or 3 divided doses on an empty stomach	6-12 hours
* All are available in generic.

Table 5. A Suggested Algorithm for Insulin Dosage Adjustment Based on Blood Glucose Determinations (blood, plasma, or serum)*

Initial doses:

Use NPH or Lente insulin, start with 0.2-0.5 U/kg.
On subsequent days increase A.M. (pre-breakfast NPH or Lente according to fasting blood glucose as follows: Give 1 U for every 20 mg/dl the fasting blood glucose (FBG) exceeds 140/mg/dl. Example: If FBG is 260 mg/dl give 6 additional U. When A.M. dose reaches 50 U, or if pre-supper hypoglycemia occurs, then reduce the A.M. dose by 20% giving that 20% before supper. Example: Patient is taking 40 U of NPH and complains of nervousness and hunger at 5:00 P.M., FBG is 210 mg/dl, reduce A.M. dose of NPH to 30 U and give 10 U before supper. Use pre-supper insulin dose to control FBG, increasing this dose by 1 U/10 mg/dl if the FBG exceeds 140.
An occasional patient will exhibit persistent fasting hyperglycemia in spite of a marked increase in the pre-supper NPH or Lente (where the pre-supper dose is equal to or greater than the pre-breakfast dose). Two procedures are indicated in such patients:
Determine whether the patient is having hypoglycemia with rebound hyperglycemia (Somogyi effect) bychecking the blood glucose one or two times between 2:00 and 6:00 A.M.
If hypoglycemia is not occurring, then move the pre-supper dose of NPH or Lente to before bedtime.
When the FBG has been optimized using the above techniques, then pre-lunch and pre-bedtime hyperglycemia is treated using regular insulin mixed with the pre-breakfast or pre-supper NPH or Lente. Dosage change is 1 U/30 mg/dl over 140.
For hypoglycemia, decrease dose by 2-4 U of NPH or regular (except for 2b above) and inquire of patient about changes in dietary intake and physical activity.

* This schedule assumes that the patient is receiving an optimum diabetic diet and that reliable plasma glucose data are available from hospital or home glucose monitoring.

From:
Diabetes Mellitus. Theory and Practice, Third Edition, Eds. Ellenberg M, Rifkin H. Medical Examination Publishing Co., Inc., New York, 1983.

Be aware that secondary failures are common, and continued patient monitoring at regular intervals is necessary.

Insulin

Insulin is required in Type 1 diabetics for even short-term survival. When obese Type 2 diabetics fail weight loss and oral hypoglycemic agents, insulin is necessary to control hyperglycemia.

Insulin may be started on an out-patient basis in the stable patient. Usually a single injection of inter mediate insulin (NPH or Lente) should be given prior to breakfast. Control may be obtained by increasing the intermediate insulin, addition of short-acting (regular) insulin, or giving a portion of the total daily insulin prior to the evening meal or, occasionally, at bedtime (see attached algorithm).

Split-dose therapy is usually necessary in Type 1 DM, and is often necessary in Type 2 patients who are difficult to control or who require large amounts of insulin (greater than 40 or 50 units).

Individual patient variations are frequent in the peak activity and duration of action of short-acting and intermediate-acting insulin, especially after longterm use of insulin. Intermediate-acting human insulin has an earlier onset and peak than beef/pork preparations.

Insulin is an appetite stimulant, especially in large doses, and makes weight reduction more difficult. This complicates therapy in the obese Type 2 diabetic, and many of these patients are on very high doses of insulin (> 100 units), with continued poor control. In the obese patient who becomes motivated to lose weight, reduction of insulin dosage is usually indicated, and this may allow further weight loss due to less appetite stimulation.

Insulin may be added to oral agents when secondary failure occurs. A simple approach is to give 10 units of NPH at bedtime and monitor FBS each morning. After 7 days, if FBS is >140, add 5 units. Continue to increase by 5 units each week until FBS is <140. When FBS is <120, reduce dose by 5 units.

Propanolol and other beta-blockers should be avoided if possible, in patients on insulin, since the warning symptoms of hypoglycemia will be masked, and dangerously low blood glucose levels can occur before the patient recognizes the problem.

Thiazide diuretics should be avoided because they increase insulin requirements and adversely affect glycemic control. Both thiazides and beta blockers adversely affect hyperlipidemia, a common coexisting disease in the diabetic. Many diabetic patients also have hypertension and are at high risk for nephropathy. The target BP in these patients is <130/85. ACE inhibitors have been shown to delay or prevent the nephropathy of DM and are therefore the treatment of choice when these conditions co-exist.

Methods of Monitoring Therapy

Signs and symptoms - particularly polyuria, polydipsia, and symptoms of hypoglycemia - should be discussed at each clinic visit.
Fasting and/or 2-hour postprandial serum glucose help determine control on the day of clinic visit. Random plasma glucose is less helpful.
Home blood glucose measuring is indicated for Type 1 diabetics and for Type 2 diabetics who are on insulin and are difficult to control. Blood glucose should be measured once daily on an alternating schedule before meals and at bedtime. The values should be recorded in a log and reviewed on each visit.
Glycosylated hemoglobin (Hgb A_1C) can be used to estimate control over the preceding 2 to 3 months, and should be checked twice a year in controlled patients and every 3 months in uncontrolled patients or after therapy has changed..

Team Approach. Members of the team include nurses for patient education and support groups, dietitions as mentioned above, physical therapists or podiatrists for on-going foot care, ophthalmologists for periodic exams to detect retinal changes at a treatable stage, and nephrologists when advanced renal impairment occurs.
Visits to ophthalmologists should occur annually. Retinal photography is indicated for any newly diagnosed diabetic, any Type 1 diabetic of 5 years or more, and all Type 2 diabetics.
A foot examination should be performed on each visit to detect early foot problems and to emphasize good foot care.
Urinalysis should be performed annually to detect proteinuria. Analysis for microalbuminuria can detect proteinuria at an earlier stage. Begin ACE inhibitor if proteinuria is detected.

References
American Diabetes Association. Standards of medical care for patients with diabetes mellitus. Diabetes Care, January 1998;21(Suppl 1):S23-S31.
Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, January 1998;21(Suppl. 1):S5-S19.
American Diabetes Association: Clinical Practice Recommendations 2000; Volume 23 Supplement 1, January 2000

M. Harper, MD
updated 8/30/05

Home

Index

Contact CCC