Steps in the Management of the Diabetic Patient − Rakyat Biologi

A. Diagnostic Examination

Any features of the clinical picture that suggest end-organ insensitivity to insulin, such as visceral obesity, must be identified. The family history should document not only the incidence of diabetes in other members of the family but also the age at onset, whether it was associated with obesity, and whether insulin was required. Other factors that increase cardiac risk, such as smoking history, presence of hypertension or hyperlipidemia, or oral contraceptive pill use, should be recorded.

Laboratory diagnosis should document fasting plasma glucose levels above 126 mg/dL or postprandial values consistently above 200 mg/dL and whether ketonuria accompanies the glycosuria. A glycohemoglobin measurement is useful for assessing the effectiveness of future therapy. Some flexibility of clinical judgment is appropriate when diagnosing diabetes mellitus in the elderly patient with borderline hyperglycemia.

Baseline values include fasting plasma triglycerides, total cholesterol and HDL-cholesterol, electrocardiography, renal function studies, peripheral pulses, and neurologic, podiatric, and ophthalmologic examinations to help guide future assessments.

B. Patient Education (Self-Management Training)

Since diabetes is a lifelong disorder, education of the patient and the family is probably the most important obligation of the clinician who provides initial care. The best persons to manage a disease that is affected so markedly by daily fluctuations in environmental stress, exercise, diet, and infections are the patients themselves and their families. The "teaching curriculum" should include explanations by the physician or nurse of the nature of diabetes and its potential acute and chronic hazards and how they can be recognized early and prevented or treated. Self-monitoring of blood glucose should be emphasized, especially in insulin-requiring diabetic patients, and instructions must be given on proper testing and recording of data. Patients should be provided with algorithms they can use to adjust the timing and quantity of their insulin dose, food, and exercise in response to measured blood glucose values. The targets for blood glucose control should be elevated appropriately in elderly patients since they have the greatest risk if subjected to hypoglycemia and the least long-term benefit from more rigid glycemic control. Advice on personal hygiene, including detailed instructions on foot care as well as individual instruction on diet and specific hypoglycemic therapy, should be provided. Patients should be told about community agencies, such as Diabetes Association chapters, that can serve as a continuing source of instruction. Finally, vigorous efforts should be made to persuade new diabetics who smoke to give up the habit, since large vessel peripheral vascular disease and debilitating retinopathy are less common in nonsmoking diabetic patients.

C. Initial Therapy

Treatment must be individualized on the basis of the type of diabetes and specific needs of each patient. However, certain general principles of management can be outlined for hyperglycemic states of different types.

1. Type 2 diabetes

a. The obese type 2 patient

The most common type of diabetic patient is obese, is non-insulin-dependent, and has hyperglycemia because of insensitivity to normal or elevated circulating levels of insulin.

(1) Weight reduction

Treatment is directed toward achieving weight reduction, and prescribing a diet is only one means to this end. Behavior modification to achieve adherence to the diet-as well as increased physical activity to expend energy-is also required. Cure can be achieved by reducing adipose stores, with consequent restoration of tissue sensitivity to insulin, but weight reduction is hard to achieve and even more difficult to maintain with our current therapies. The presence of diabetes with its added risk factors may motivate the obese diabetic to greater efforts to lose weight.

(2) Hypoglycemic agents

Monotherapy with metformin (or Α-glucosidase inhibitors) is the first-line therapy in the obese patient with mild diabetes if pharmacotherapy is required since they are not associated with weight gain or drug-induced hypoglycemia. If metformin therapy (combined with a weight reduction regimen) is inadequate to control blood glucose levels, then a thiazolidinedione or a sulfonylurea should be added. Some individuals may require metformin, a thiazolidinedione, and a sulfonylurea to achieve adequate glycemic control.

Insulin therapy should be instituted if the combination of these three drugs fails to restore euglycemia. Weight-reducing interventions should continue and may allow for simplification of this regimen in the future.

b. The nonobese type 2 patient

In the nonobese diabetic, mild to severe hyperglycemia is usually due to refractoriness of B cells to glucose stimulation. Treatment depends on whether insulinopenia is mild (type 2 or mild type 1 in partial remission) or severe, with ketoacidosis.

(1) Diet therapy-

If hyperglycemia is mild, normal metabolic control can occasionally be restored by means of multiple feedings of a diet limited in simple sugars and with a caloric content sufficient to maintain ideal weight. Restriction of saturated fats and cholesterol is also strongly advised.

(2) Oral hypoglycemic agents

When diet therapy in nonketotic type 2 patients is not sufficient to correct hyperglycemia, a trial of sulfonylureas is often successful in reducing the glycohemoglobin concentration below 9.5%. Once the dosage of one of the more potent sulfonylureas reaches the upper recommended limit in a compliant patient without maintaining fasting blood glucose below 140 mg/dL during the day, combination therapy with metformin (up to 1000 mg twice daily) or a thiazolidinedione-or both-should be tried. When the patient fails the combination of these three drugs, insulin therapy is indicated.

c. Treatment of type 2 diabetes with insulin

When the combination of metformin, sulfonylurea, and a thiazolidinedione fails and patients with type 2 diabetes require insulin, various insulin regimens may be effective. A single nighttime injection of NPH or insulin glargine can be added and titrated to achieve target fasting blood glucose values while continuing the oral antidiabetic medications. If the patient does not achieve target glucose levels during the day, daytime insulin treatment can be initiated. A convenient insulin regimen under these circumstances is a split dose of 70/30 NPH/regular mixture (or Humalog Mix 75/25 or NovoLogMix 70/30) before breakfast and before dinner. If this regimen fails to achieve satisfactory glycemic goals or is associated with unacceptable frequency of hypoglycemic episodes, then a more intensive regimen of multiple insulin injections can be instituted. Metformin principally reduces hepatic glucose output and the thiazolidinediones improve peripheral resistance, and it is a reasonable option to continue these drugs when insulin therapy is instituted. The sulfonylureas also have been shown to be of continued benefit. Thus, the continued use of the oral drugs may permit the use of lower doses of insulin and simpler regimens.

2. Type 1 diabetes

Traditional once- or twice-daily insulin regimens are usually ineffective in type 1 patients without residual endogenous insulin. In these patients, information and counseling based on the findings of the DCCT should be provided about the advantages of taking multiple injections of insulin in conjunction with self-blood glucose monitoring. If near-normalization of blood glucose is attempted, at least three or four measurements of capillary blood glucose and three or four insulin injections are necessary.

A combination of rapid-acting insulin analogs and long-acting insulins (ultralente or insulin glargine) allows for more physiologic insulin replacement. The rapid-acting insulin analogs have been advocated as a safer and much more convenient alternative to regular human insulin for preprandial use. In a study comparing regular insulin with insulin lispro, daily insulin doses and hemoglobin A_1c levels were similar, but insulin lispro improved postprandial control, reduced hypoglycemic episodes, and improved patient convenience compared with regular insulin. However, because of their relatively short duration (no more than 3-4 hours), the rapid-acting insulin analogs need to be combined with longer-acting insulins to provide basal coverage and avoid hyperglycemia prior to the next meal. In addition to carbohydrate content of the meal, the effect of simultaneous fat ingestion must also be considered a factor in determining the ultra-fast-acting insulin dosage required to control the glycemic increment during and just after the meal. With low-carbohydrate content and high-fat intake, there is an increased risk of hypoglycemia from insulin lispro within 2 hours after the meal. Table 27-11 illustrates some regimens that might be appropriate for a 70-kg person with type 1 diabetes eating meals providing standard carbohydrate intake and moderate to low fat content.

Table 27-12. Prebreakfast hyperglycemia: Classification by blood glucose and insulin levels.

	Blood Glucose (mg/dL)					Free Immunoreactive Insulin (microunit/mL)
	10:00 PM	3:00 AM	7:00 AM	10:00 PM	3:00 AM	7:00 AM
Somogyi effect	90	40	200	High	Slightly high	Normal
Dawn phenomenon	110	110	150	Normal	Normal	Normal
Waning of insulin dose plus dawn phenomenon	110	190	220	Normal	Low	Low
Waning of insulin dose plus dawn phenomenon plus Somogyi effect	110	40	380	High	Normal	Low

Multiple injections of NPH insulin (or twice-daily ultralente insulin) can be mixed in the same syringe as the insulin lispro, insulin aspart, and insulin glulisine. Insulin glargine is usually given once in the evening to provide 24-hour coverage. This insulin cannot be mixed with any of the other insulins and must be given as a separate injection. There are occasional patients in whom insulin glargine does not seem to last for 24 hours, and in such cases it needs to be given twice a day.

Continuous subcutaneous insulin infusion (CSII) by portable battery-operated "open loop" devices currently provides the most flexible approach, allowing the setting of different basal rates throughout the 24 hours and permitting patients to delay or skip meals and vary meal size and composition. The dosage is usually based on providing 50% of the estimated insulin dose as basal and the remainder as intermittent boluses prior to meals. For example, a 70-kg man requiring 35 units of insulin per day may require a basal rate of 0.7 units per hour throughout the 24 hours with the exception of 3 am to 8 am, when 0.8 units per hour might be appropriate (for the dawn phenomenon). The meal bolus would depend on the carbohydrate content of the meal and the premeal blood glucose value. One unit per 15 g of carbohydrate plus 1 unit for 50 mg/dL of blood glucose above a target value (eg, 120 mg/dL) is a common starting point. Further adjustments to basal and bolus dosages would depend on the results of blood glucose monitoring. The majority of patients use the rapid-acting insulin analogs in the pumps. One of the more difficult therapeutic problems in managing patients with type 1 diabetes is determining the proper adjustment of insulin dose when the prebreakfast blood glucose level is high. Occasionally, the prebreakfast hyperglycemia is due to the Somogyi effect, in which nocturnal hypoglycemia leads to a surge of counterregulatory hormones to produce high blood glucose levels by 7 am. However, a more common cause for prebreakfast hyperglycemia is the waning of circulating insulin levels by the morning. Also, the "dawn phenomenon"-reduced tissue sensitivity to insulin between 5 am and 8 am-is present in as many as 75% of type 1 patients and can aggravate the hyperglycemia.

Table 27-12 shows that diagnosis of the cause of prebreakfast hyperglycemia can be facilitated by self-monitoring of blood glucose at 3 am in addition to the usual bedtime and 7 am measurements. This is required for only a few nights, and when a particular pattern emerges from monitoring blood glucose levels overnight, appropriate therapeutic measures can be taken. The Somogyi effect can be treated by eliminating the dose of intermediate insulin at dinnertime and giving it at a lower dosage at bedtime or by supplying more food at bedtime. When a waning insulin level is the cause, then either increasing the evening dose or shifting it from dinnertime to bedtime (or both) can be effective. A bedtime dose either of insulin glargine or of NPH insulin made from pork insulin provides more sustained overnight insulin levels than human NPH or human ultralente insulin and may be effective in managing refractory prebreakfast hyperglycemia. If this fails, insulin pump therapy may be required. When the dawn phenomenon alone is present, the dosage of intermediate insulin can be divided between dinnertime and bedtime; when insulin pumps are used, the basal infusion rate can be increased (e.g., from 0.8 unit/h to 0.9 unit/h from 6 am until breakfast).