Diabetes Mellitus: A Brief Overview
Diabetes mellitus, commonly known as diabetes, is a metabolic disease characterized by the body’s inability to adequately utilize carbohydrates, fats, and proteins due to insufficient insulin production or ineffective insulin action. It is a chronic condition that requires continuous medical care. The increasing number of patients worldwide, including in our country, has led to a growing burden in terms of both high costs and the development of other complications associated with the onset or chronic phase of the disease. It is crucial to provide effective treatment to address these challenges.
Purpose and Approach in Treatment
The aim of the treatment is to ensure the control of sugar levels in the body throughout the day, reduce the risk of developing other diseases related to sugar, prevent small and large vascular diseases, correct accompanying problems, and thus improve the quality of life in diabetes.
MEDICAL TREATMENT IN TYPE 1 DIABETES:
The only drug used in the treatment of type 1 diabetes is insulin. Insulins are categorized based on their duration of action: rapid, short, intermediate, long-acting, and mixed insulins. Intensive insulin therapy (basal-bolus) is essential in the treatment of type 1 diabetes. According to this method, subcutaneous insulin therapy three times a day or continuous subcutaneous insulin administration (insulin pump) is applied. Short and intermediate-acting human insulins, as well as rapid-acting and long-acting analog insulins, are used for this purpose.
MEDICAL TREATMENT IN TYPE 2 DIABETES:
More than 90% of all diabetics are type 2 diabetics, and this group is generally overweight or obese, unlike type 1 diabetic patients. Early achievement of good blood sugar control reduces or delays the development of complications associated with diabetes.
There is no drug that can replace positive lifestyle changes in the treatment of diabetes. Lifestyle changes have a positive effect not only on blood sugar but also on all other risk factors. Recommendations for regulating dietary habits and achieving an adequate level of physical activity, quitting smoking, etc., should be individually determined based on the patient’s characteristics. While blood sugar is normalized, lipid levels and blood pressure should also be regulated.
Blood Sugar Targets in Type 2 Diabetes:
The HbA1C (average blood sugar level for the last three months) target in type 2 diabetes is ≤ 7%, ≤ 6.5% in young patients without cardiovascular disease risk, and ≤ 7.5% in the elderly group with cardiovascular disease risk. Early achievement of good sugar control reduces disorders that can occur in small and large blood vessels. Especially in patients with a high risk of cardiovascular disease, sudden sugar drop can increase the mortality rate. Therefore, avoiding hypoglycemia (blood sugar level below 70 mg/dl) is one of the main goals, especially in patients with other diseases developed due to diabetes.
There are mainly four groups of drugs that reduce blood sugar taken orally in the treatment of type 2 diabetes:
- Drugs that reduce insulin resistance (increase insulin sensitivity)
- Insulin secretagogues
- Drugs that reduce carbohydrate absorption from the intestines
- Incretin-based therapies
A: Drugs that Reduce Insulin Resistance (Increase Insulin Sensitivity):
- Metformin: The first drug to be used in individuals diagnosed with type 2 diabetes along with lifestyle changes is metformin. It lowers HbA1C levels by approximately 1-2%. It does not cause weight gain; it may even induce weight loss by reducing appetite. Side effects such as gas, bloating are generally temporary. Diarrhea and a metallic taste in the mouth are the main side effects. It should not be used in cases of kidney dysfunction (serum creatinine in men ≥ 1.5 mg/dl, in women ≥ 1.4 mg/dl), chronic alcoholism, liver disease, congestive heart failure, heart attack, chronic lung disease, major surgeries, infectious diseases, or reduced tissue perfusion due to intravenous drug administration (should be discontinued at least 3 days before).
- Thiazolidinediones (Pioglitazone): HbA1C lowering effect: 1-2%. Main side effects include weight gain, fluid retention (edema), increased risk of fractures due to osteoporosis, especially in postmenopausal women and also in men. It should not be used in heart failure.
B. Insulin Secretagogues:
- Meglitinides: They are short-acting insulin secretagogues. There are two different pharmacological structures as nateglinide and repaglinide. They are effective on postprandial blood sugar. HbA1C lowering effects are reported to be 0.8-2%. There is a low risk of hypoglycemia.
- Sulfonylureas: Short and intermediate-acting ones are used today. HbA1C lowering effects: 1-2%. The main side effects are hypoglycemia, weight gain, and rarely allergic reactions. It should not be used in type 1 diabetes, liver and kidney insufficiency, pregnancy, severe infection, trauma, and surgical interventions. It is taken on an empty stomach before meals. Usually given once or twice a day.
C. Drugs that Reduce Carbohydrate Absorption from the Intestines:
Alpha-Glucosidase Inhibitors: Acarbose is especially effective on postprandial blood sugar. HbA1C lowering effect: 0.5-1%. It does not cause weight gain. In fact, it contributes to weight loss by giving a feeling of fullness. Excessive gas is the most important side effect.
D. Incretin-Based Therapies (Gastrointestinal Hormone Group that Increases Insulin Secretion from the Pancreas after Meals):
The main injectable ones are Exenatide, Liraglutide, and oral ones are Sitagliptin, Vildagliptin, Saxagliptin. They are effective on postprandial sugar. HbA1C lowering effect: 1-2%. They do not cause weight gain; on the contrary, weight loss is significant, especially with exenatide and liraglutide, due to decreased appetite and mild nausea. The blood sugar-lowering effect of these oral medications is lower than that of injectables.
INSULIN TREATMENT IN TYPE 2 DIABETES:
Patients starting insulin should be informed about recognizing, preventing, and treating hypoglycemia. Patients should be educated about dose adjustments and their effects. Insulin and thiazolidinediones should not be given together in patients with heart failure. Sugar monitoring should continue in patients who have achieved the ideal blood sugar level with insulin therapy. Hypoglycemic attacks can occur in 50% of individuals, and insulin dose reduction may be required again.
SURGICAL TREATMENT IN TYPE 2 DIABETES:
Bariatric surgery, or obesity surgery, in addition to weight loss, also improves a significant portion of patients with type 2 diabetes, hypertension, obstructive sleep apnea, hyperlipidemia, and other comorbidities. The mechanism behind this improvement is changes in gut hormones that regulate insulin production and action, in addition to weight loss and restricted food intake.
The proven positive effects of bariatric surgery on type 2 diabetes have led to the development of laparoscopic metabolic surgery. Laparoscopic Sleeve Gastrectomy + Duodenoileal Interposition, Laparoscopic Sleeve Gastrectomy + Duodenojejunal Bypass, Laparoscopic Sleeve Gastrectomy + Jejunoileal Interposition are metabolic surgeries developed in this context. These operations can be applied not only in obese patients but also in normal-weight patients for the treatment of type 2 diabetes.
With metabolic surgery:
- The longer the duration of diabetes and the worse the control, the less successful the improvement:
- Chance of remission (recovery) is 50% in patients with HbA1c > 10%
- 77% in patients with HbA1c 6.5-7.9%
- Remission is 75% if the duration of diabetes is > 5 years
- Remission is 95% if the duration of diabetes is < 5 years
- Success decreases with age.
- Maintaining weight loss facilitates diabetes control.
In type 1 diabetes or in type 2 diabetes patients using insulin for more than 10 years, when kidney failure due to diabetes develops, pancreas transplantation is performed simultaneously with kidney transplantation. However, pancreas transplantation is not performed just to get rid of insulin for individuals with well-controlled diabetes.
PANCREATIC ISLET CELL TRANSPLANTATION:
Pancreatic islet cell transplantation is an experimental procedure currently applied in selected patients, offering new and promising possibilities for the treatment of type 1 diabetes.