In case of diabetes type 2, initially the body tries to overcome the raised blood sugar levels by secreting more insulin. However, after some time due to continuously raised blood sugar levels the insulin sensitivity (amount of blood sugar lowered by 1 unit of insulin) goes down, and insulin resistance develops.
Increased amount of cortisol, adrenaline, glucagon secretion due to stress and lack of proper diet and exercise also contributes to insulin resistance.
There are several signs and symptoms which are associated with insulin resistance. For example, raised BMI, increased waist circumference, dark velvety skin around skin folds, especially the neck and axilla (acanthosis nigricans).
Two main drugs which are used to manage insulin resistance are Metformin and PPAR gamma agonist Pioglitazone.
Metformin lowers insulin resistance by countering the secretion of cortisol hormone. It thus lowers the level of glycogenolysis and gluconeogenesis. It is accordingly given as per the circadian rhythm of cortisol secretion
Fig: Circadian rhythm of cortisol secretion
Normally, cortisol should dip in the evening, to rise again from early morning. However, due to modern lifestyle of having late dinners and partying till late at night, cortisol levels fail to fall, and blood sugar levels remain elevated.
Metformin is therefore prescribed in the evening (post evening snack or post dinner). The total daily dose of insulin can be upto 2 gm in a day. It can be given into divided doses of 500 mg to 1 gm.
Typically one would start with 500 mg after dinner or evening snack. This can be increased to 1 gm if morning fasting sugar is still on the higher side. To increase Metformin dose, another 500 mg can be added after lunch, and then post breakfast.
Can we see a pattern here. We are going from night to day. When we supplement steroids we go from day (breakfast) to night (dinner).
Since metformin reduces cortisol secretion it also causes increased salt and water excretion from the body and mild to moderate weight loss. Metformin in excess and in patients with pre-existing adrenal fatigue (thin, debilitated patients with chronic illnesses, autoimmune issues, senior citizens), Metformin can lead to signs and symptoms of adrenal insufficiency, for example: bitter taste, epigastric pain, diarrhea, hyponatremia (most dreaded complication, especially in senior citizens who are on regular metformin and have developed some intercurrent illness like a viral fever which has precipitated adrenal insufficiency).
In such a case, metformin dose might have to be reduced or completely stopped. Or even steroids need to be supplemented.
Here there are two things that need to be kept in mind. First, if during a critical illness ACTH levels are coming within normal range with the short synacthen test, there actually might be an insufficiency. Because, ideally ACTH levels should be on the higher side during a critical illness. Second, elderly people might appear obese due to poor tone of abdominal muscles, as a result of gluconeogenesis, and we might falsely label them as obese, and start with metformin.
Metformin thus is recommended in people who are young, overweight, with signs of increased cortisol secretion (metabolic syndrome), and signs of insulin resistance.
As Metformin acts by reducing cortisol secretion, it doesn’t cause hypoglycemia. It only doesn’t allow blood sugar levels to rise.
Insulin Resistance in Type 2 Diabetes
In the early stages of type 2 diabetes, the body attempts to manage elevated blood sugar levels by secreting more insulin. However, over time, as blood sugar levels remain persistently high, insulin sensitivity decreases (meaning the amount of blood sugar lowered by one unit of insulin goes down), leading to the development of insulin resistance.
Increased levels of cortisol, adrenaline, and glucagon—often due to stress, poor diet, and lack of exercise—also contribute to insulin resistance.
Signs and Symptoms of Insulin Resistance
Several signs and symptoms are associated with insulin resistance, including:
- Raised BMI
- Increased waist circumference
- Dark, velvety skin around skin folds, especially the neck and axilla (acanthosis nigricans)
Medications for Managing Insulin Resistance
Two main drugs used to manage insulin resistance are Metformin and the PPAR gamma agonist Pioglitazone.