Hyperinsulinemia is a condition where the amount of insulin produced by the pancreatic β cells is higher than what is considered normal. On its own, it is not indicative of diabetes, but hyperinsulinemia is frequently associated with type 2 diabetes.
Interestingly, there are both good and bad consequences of hyperinsulinemia. The figure below, provided by the American Association of Clinical Endocrinologists (AACE), offers excellent explanations of how hyperinsulinemia can help maintain good blood sugar levels, even after insulin resistance has developed, and how this benefit can turn sour.
In most cases, hyperinsulinemia is caused by insulin resistance—a condition where our bodies do not respond well to the effect of insulin. This means that it takes more insulin to maintain normal blood sugar levels, and so our pancreatic β cells are forced to make more insulin (the rising cyan line in the figure). As a result, even after insulin resistance (the rising blue line) has developed, hyperinsulinemia can help our postprandial and fasting blood sugar levels (the red line and the green line) remain normal for up to 5 years before the onset of type 2 diabetes (ref 1 and 2) .
Things can turn bad if our β cells keep overworking, producing high amounts of insulin.
Insulin resistance may eventually lead to the onset of type 2 diabetes. This happens when our pancreatic β cells can no longer produce enough insulin (the descending cyan line) to cancel the effect of insulin resistance (the blue line). Consequently, our blood sugar levels, postprandial and fasting, rise continuously as our pancreatic β cells produce less insulin.
The reason that β cells are unable to produce enough insulin is also clearly illustrated in the figure. As β cells die, the β cell mass (the total number of β cells, the purple line in the figure) decreases over time. Surprisingly, after a diagnosis of type 2 diabetes (year 0 in the figure), insulin resistance no longer accounts for rising blood sugar levels. As you can see, the blue line remains at the same height while the red and the green lines keep going up. In other words, what makes the condition of a diabetic patient worse is a decreasing β cell mass (the descending purple line), not insulin resistance.
In the past, we did not know how overworking kills pancreatic β cells. Thanks to diligent scientists (me included), now we understand that overworking induces Endoplasmic Reticulum (ER) stress and oxidative stress, the two leading causes of pancreatic β cell death (ref 3).
Next time we will connect the dots between β cell death and ER stress/oxidative stress.
1. Costes et al. β-Cell Failure in Type 2 Diabetes: A Case of Asking Too Much of Too Few? Diabetes. 2013, 62:327–335.
2. Kitamura T. The role of FOXO1 in β-Cell failure and type 2 diabetes mellitus. Nat Rev Endocrinol. 2013; 9:615–623.
3. Hasnain, Z. et al. Oxidative and endoplasmic reticulum stress in β-cell dysfunction in diabetes. J Mol Endocrinol. 2016, 56: R33-R54