Insulin and Drug Therapy
Type I diabetes typically involves damage to the insulin secreting cells of the pancreas, which can occur for a many reasons, the most common of which is believed to be attack by the body’s own immune system. This damage is typically permanent and irreversible. For this reason, Type I diabetes needs to be controlled with insulin. Nevertheless, management of the insulin regime, with an eye to keeping blood sugars at optimal levels, greatly reduces the tendency to diabetic complications. Even patients with poor blood sugar control and many signs and symptoms of diabetic complications should not despair. Instituting a proper insulin management regime can result in improvements in symptoms and blood parameters for this group of individuals as well.
Type II diabetes is best managed without insulin. Remember, Type II diabetics typically have excess insulin and insulin resistance. Diet, lifestyle, nutritional supplements, and traditional herbs are very good approaches to managing Type II diabetes. If these first-line approaches are not as effective as desired, oral hypoglycemic medications, such as Metformin, may be indicated. Instituting oral hypoglycemic drugs does not mean that you should disregard natural therapies. Many diabetics do very well with a complementary combination of healthy diet, nutritional supplements, healthy lifestyle, and pharmaceutical medications. Naturopaths are well versed in managing patients with these types of programs.
Type I Diabetes
Conventional treatment of Type I IDDM usually focuses on insulin therapy to replace what is no longer being produced by the pancreas. Regular monitoring of both insulin and blood glucose enables the diabetic patient to regulate levels throughout the day, accommodating for food intake and activity levels.
Intensive Insulin Therapy
For intensive care in Type I patients, it is recommended that blood is tested 4 to 8 times daily to assess blood sugar levels before and after eating. The patient is asked to measure the exact amount of carbohydrates ingested or use the diabetic exchange system to make exact estimates on insulin adjustments.
Advances in pharmaceutical treatments, combined with the availability of self-blood monitoring (SMBG) and multiple-dose insulin regimens, have led to significant improvement in giving Type I diabetics better glycemic control. Tighter control of blood glucose levels has been shown to reduce the risk of long-term diabetic complications. The Diabetes Control and Complication Trial (DCCT) showed a 34% to 76% reduction in clinically meaningful retinopathy in Type I diabetic patients who used intensive diabetes monitoring compared to patients who did not.
Nocturnal Hyperglycemia
Although high blood sugar at any time, day or night, increases the risk of secondary complications, this is of particular concern during the night, when most diabetics are not monitoring their blood glucose levels. One way to stabilize levels overnight is to split an insulin dose, taking the first half before dinner and the second before bed. The latter injection will cause insulin levels to peak early in the morning, preventing nocturnal hyperglycemia.
Type II Diabetes
Pharmacological drugs have demonstrated their effectiveness in preventing diabetic complications and in decreasing glycosylated-hemoglobin. However, they remain of limited use in enabling NIDDM patients to achieve tight control of blood sugar levels.
Insulin
Insulin is one type of pharmacological agent used in NIDDM. Eighty percent of the cell membranes in the body become highly permeable to glucose within seconds of insulin binding to its receptors; rapid entry of glucose ensues, which is used in the formation of substrates for metabolism. Thin diabetic patients respond quite well and have decreased microvascular complications.
The disadvantages of using insulin in NIDDM patients include the risk of hypoglycemic episodes that can lead to a coma, and the increased risk of macrovascular complications. The use of insulin can cause weight-gain, which is a problem in perpetuating insulin resistance itself. Only a minority of NIDDM patients can take insulin since it is usually not effective in obese and overweight patients.
Medications
Sulfonylureas
Sulfonylureas, or sulfa drugs, work by stimulating insulin secretion from the beta cells of the pancreas. Following long-term use, it may also affect extra-pancreatic functions, increasing peripheral sensitivity to insulin and decreasing hepatic glucose production. An advantage to sulfonylureas is the availability of multiple formulations that are relatively inexpensive, but after initial success, sulfonylureas are of limited effectiveness. Furthermore, sulfonylureas are contraindicated in liver, kidney, and thyroid diseases.
The limited effectiveness of sulfonylureas was demonstrated in a study with Glimepiride. Five thousand patients with Type II diabetes demonstrated a decrease of fasting glucose by 43 to 74 mg/dL more than with a placebo. The administration of Glimepiride also decreased HbA1c values by 1.2% to 1.9%. However, after that initial success, sulfonylureas are completely ineffective in 30% of patients. Adequate control in their long-term use occurred in only 20% to 30% of patients.
Primary and secondary failure can occur with all oral agents used in the treatment of NIDDM. One study showed that the rate of deaths due to heart attack was 2.5 times greater in patients who had used sulfonylureas for the treatment of glycemia than in the group treated with diet modifications alone. Currently, there are warning labels for cardiac death on all sulfonylureas and Metformin. However, one UK study found no correlation between increased cardiovascular death and sulfonylurea use.
Metformin
Metformin, a biguanide, is the drug of choice for obese NIDDM patients. A relatively new pharmacological agent, Metformin is believed to potentiate insulin and increase insulin receptor sites, independent of pancreatic function. It also leads to weight-loss, which may be another contributing factor in its mechanism.
The effectiveness of Metformin has been demonstrated in pharmacological studies. In one study, 228 patients had an HbA1c value of 9.43%; after 3 months of treatment, this decreased to 8.7%; after 6 months to 8.3%; and after 9 months to 8.72%. A slight rise in HbA1c value after long-term administration was noted. Although Metformin is often prescribed following secondary failure of sulfonylureas, it is rarely effective.
The most common side effect is diarrhea. Metformin also decreases absorption of vitamin B-12 and folic acid. Patients with diabetic neuropathy may have symptoms associated with both diabetes and a deficiency in vitamin B-12 due to its use. It is important to determine whether the hyperglycemia or the pharmacological agent will present more problems to a patient with diabetic nephropathy.
Metformin is contraindicated in kidney disease and a rare fatal complication of its administration is lactic acidosis.
Alpha-glucosidase Inhibitors
A newly developed pharmacological agent used in the treatment of NIDDM is alpha-glucosidase inhibitors. These work in the small intestine by inhibiting the enzyme glucosidase, thus delaying postprandial glucose absorption.
In a study of 1,027 patients given alpha-glucosidase inhibitors, a significant decrease in blood sugar levels was found. However, gastrointestinal side effects prevented one-third of the patients from continuing this drug for 1 year.
In addition to its many side effects, alpha-glucosidase inhibitors are also very costly, and have marginal clinical relevance.
Cautions, Contraindications, and Side-Effects
When considering oral pharmacological treatment, the risk of side effects must be assessed since tissue damage may be caused both by hyperglycemia and by pharmacological agents used in diabetic treatment. It is important to determine which may cause more harm.
Sulfonylureas can cause kidney damage and may also be toxic to the pancreas. These drugs are contraindicated in patients with liver, thyroid, or kidney diseases. Interestingly, all three organs are involved in diabetes (the liver produces receptor sites, the thyroid prevents excessive weight gain, and the kidneys maintain blood pressure control). In particular, impaired kidney function in diabetics, resulting from either hyperglycemia or pharmaceuticals, causes progressive deterioration of blood pressure control. One UK study that divided subjects into two groups with greater or lesser control of their blood pressure found that the group with tighter control had a decrease in almost all microvascular complications: a 25% decrease in diabetic-related endpoints, a 32% decrease in deaths related to diabetes, a 44% decrease in strokes, and a 39% decrease in microvascular endpoints. The tighter control group also enjoyed a significant difference in the long-term perspective of their lives.
SIADH (syndrome of inappropriate anti-diuretic hormone secretion) can also occur in the use of sulfonylureas, manifested by water-retention and hyponatremia. Since many diabetic patients have edema due to nephropathy, pharmacological agents must be ruled out as the cause of edema in these patients. In some cases, edema may be relieved by discontinuing the use of sulyfonylureas and using a combination of herbs (jambul, devil’s club, globe artichoke, milk thistle, and nopal).
Despite the use of pharmaceutical drugs for Type II diabetes in the last 30 years, fewer than 25% of NIDDM patients have been able to achieve normal glycosylated hemoglobin levels. Elevated glycosylated hemoglobin and poor glycemic control are associated with increased mortality. Hypoglycemic deaths due to the use of oral hypoglycemics have also been reported. Other adverse effects of pharmacological treatment include jaundice, decreased RAI-uptake of the thyroid, weight gain, chronic hyperinsulinemia, severe insulin resistance, and possibly beta cell exhaustion. Thus, if the number of diabetes-associated deaths is to be decreased, advances in the effectiveness of treatments are necessary.
