Are Leg Cramps Caused by Diabetes?

Leg cramps/muscle cramps/charley horses are a frequent manifestation of diabetes mellitus (DM). The subject of debate: are these leg cramps caused by DM or not? Straight from the horse’s mouth: Yes, they can be! (1), ( 2)

There could be many reasons of leg cramps due to diabetes. Some of the most common being

Dehydration and electrolyte (mineral) imbalance secondary to high blood glucose levels (hyperglycemia) prompting excessive urination (polyuria) and the subsequent passage of glucose (glycosuria) and electrolytes in urine (scroll down)
Peripheral neuropathy
Peripheral vascular disease
Hypoglycemia secondary to insulin and oral anti-diabetic medications

So, how do you define leg cramps? Leg cramps are instantaneous, involuntary (automatic, not under your control), and sustained painful contractions of one or more groups of muscles. These are usually felt in the calves and can extend up to the feet. Diabetics usually describe pain being worse at night (nocturnal leg cramps).

Mechanisms and Cellular Events Underlying Leg Cramps in Diabetes

A) Leg Cramps Secondary to Polyuria and Consequent Electrolyte Disturbances

Dehydration secondary to polyuria causes leg cramps via inducing electrolyte disturbances, most commonly hyponatremia (a decrease in blood sodium levels). Glucose is an osmotic substance; when the blood sugar levels rise high enough, the glucose starts excreting into the urine (glycosuria), and along with it, it carries sodium and water, predisposing to hyponatremia (5). This is hyperglycemia-induced-osmotic-diuresis (i.e. increased blood glucose causing an excessive excretion of glucose in urine along with electrolytes and water).

Diuresis is the excessive production of urine. Osmotic diuresis is excessive urination due to the presence of osmotic substances within the kidney tubes. This osmotic diuresis draws out the fluid from the spaces between the cells (called interstitial fluid) including the muscle cells, thereby increasing the osmolarity of the extracellular fluid (the fluid outside the cells; aka ECF). As a rule of thumb, an INCREASE in the ECF osmolarity (the solute concentration of a solution), SHRINKS the cells (muscle cells here) and vice versa (as the water will move out of the cells to compensate for the increased ECF solutes (or less ECF water).

The purpose of this detailed description is that these sequences of events will eventually culminate in muscle cramps. Let us see how! Because of the osmotic shifts, the calcium pump inside the muscle becomes malfunctioned, so that the calcium remains bound to troponin, resulting in a sustained muscle contraction (i.e. muscle cramp). FYI: In order for a normal muscle contraction to occur, the calcium ion needs to bind to a protein of the muscle, called troponin C. However, when this calcium detaches from troponin, the muscle is relaxed.

The other proposed mechanism of electrolyte imbalance-inducing leg cramps in DM is hypomagnesemia (reduced magnesium levels in the blood). The occurrence of hypomagnesemia in DM has a multifactorial basis. Some of the common factors include:

Hyperglycemia-induced-osmotic-diuresis
Insulin deficiency: Because insulin enhances the reabsorption or re-uptake of magnesium (Mg) via the kidneys so that more Mg is available in the blood: ↓Insulin = ↓Mg (6)
Various other causes

How does Hypomagnesemia Contribute to Leg Cramps in Diabetes

Since magnesium is imperative for the normal neuromuscular transmission, a deficiency of magnesium is likely to cause leg cramps (7). Mg deficiency also results in potassium deficiency (hypokalemia), further adding an insult to an injury. This hypokalemia aggravates the leg cramps additionally.

B) Leg Cramps Secondary to PVD

Peripheral vascular disease (PVD) or peripheral arterial disease (PAD) is a narrowing of the arteries of the legs, which leads to severe muscular cramps in the calves, thighs, or hips while walking, mounting stairs, or exercising, popularly called as intermittent claudication. However, claudication is not similar to the resting nocturnal leg cramps.

When leg cramps result from diabetic PVD, they are because of the lack of sufficient blood being supplied to the arteries of the legs due to the narrowing of the arteries by atheromatous (fibrous fatty) plaques containing cholesterol, LDL, fatty acids, inflammatory cells, and a protein called collagen.

Secondly, diabetics with poorly controlled blood glucose levels tend to have elevated levels of C-reactive protein (CRP). CRP is a heralding inflammatory marker and a major culprit behind atherosclerosis (hardening of the arteries) and PVD (3). This CRP binds to the oxidized LDL in atheromatous plaques and induces further inflammatory damage to the arterial wall. To boot, CRP also stops the production of a substance called nitric oxide (a vasodilator substance that widens and relaxes the arteries). Hence, it is quite evident that the diameter of the arteries, including the leg arteries, will reduce more leading to more claudication initially and then as the disease progresses, more resting legs cramps, specifically at night (4). It is crucial to note that although PVD can give rise to the resting leg cramps; these cramps are different from those due to intermittent claudication (a hallmark of PVD).

C) Leg Cramps secondary to Peripheral Neuropathy

Peripheral neuropathy is damage to the peripheral nerves traveling from the spinal cord up to the peripheries (rest of the body). Because of damage to the peripheral nerve/nerves, the messages sent from the brain to the periphery go haywire and the diabetics end up getting intense, burning pain sensations in the legs and or feet in the absence of a stimulus (allodynia). Albeit, diabetic peripheral neuropathy usually causes numbness (loss of sensation), tingling (pins and needles), and muscle weakness, sharp pains or cramps are also one of the reported symptoms of diabetic neuropathy (called as painful diabetic neuropathy). It has a preference to feet and legs (affected before) than hands and arms.

The Anatomy of Leg Cramps

Anatomically speaking, a cramp occurs due to constant stimulation of the reflex arc. A reflex arc is a neural pathway, which regulates a reflex action. It comprises of a sensory nerve (a nerve that conveys messages from the periphery to the central nervous system), a motor nerve (a nerve that carries information from the central nervous system to the periphery), with the muscle that it supplies, and a junction called synapse in between the two nerves. Let us get this straight! Imagine what happens when a pin pricks your foot. Your foot gets an alarm through the sensory neuron that you have encountered a painful stimulus and you suddenly withdraw your foot from the painful stimulus. This is what makes up a reflex arc. The proposed mechanism for a muscle cramp is that the repetitive stimulation of a muscle that is already contracted sets off a reflex arc that is constantly conveying contraction signals back and forth from the muscle and then back to it, which ultimately culminates in a sustained, involuntary contraction of the muscle (i.e. a cramp).

Take Home Message

If you are a diabetic and suffering from leg cramps, do not take it with a pinch of salt. Consult your doctor to detect the possible etiology (cause) of your leg cramps and managed accordingly.

References

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