Blood glucose fluctuation is often thought of as the first cause of fatigue in diabetes. But the authors of a study of 155 adults with type 2 diabetes suggested that blood glucose was the cause of fatigue in only 7 percent of participants. These findings suggest that diabetes fatigue may not be necessarily linked to the condition itself, but perhaps with other symptoms of diabetes.
As in other conditions, fatigue in people with diabetes may be caused by a variety of lifestyle, nutritional, medical, psychological, glycemic/diabetes-related, endocrine, and iatrogenic factors.
Non-Endocrine Diabetes fatigue syndrome (DFS)
Non-endocrine factors that may contribute to DFS include an unhealthy lifestyle, inappropriate diet, and suboptimal mental health. Lack of physical conditioning, poor sleep hygiene, substance abuse (including excessive alcohol, caffeine), and drug withdrawal may lead to DFS.
Unhealthy diets, which may lead to macronutrient or micronutrient malnutrition or starvation ketosis, can also precipitate DFS.
Common medical conditions, such as anemia, dyselectrolytemia, and multiple vitamin deficiencies, are also characterized by fatigue. Anemia is not caused by diabetes, but it frequently occurs in people with diabetes and is a common cause of fatigue. A history of breathlessness on exertion, excessive blood loss, worm infestation, and pallor on examination suggest anemia. People with diabetes are at increased risk for thyroid diseases, especially hypothyroidism. A sluggish thyroid together with diabetes can be another cause. Dyselectrolytemia usually leads to neurological symptoms and signs. Proximal muscle weakness, together with musculoskeletal aches, pains, and easy fatigability, implies vitamin D deficiency.
At times, DFS may be worsened by psychological impairment. Diabetes distress is defined as an emotional response, characterized by extreme apprehension, discomfort, or dejection due to a prescribed inability to cope with the challenges and demands of living with diabetes. This adjustment disorder is characterized by a discomfort disorder that in turn is characterized by discomfort, and it may be reported as fatigue, possibly contributing to, overlapping with, or mimicking DFS. Yet another differential diagnosis of fatigue may be major depressive disorder.
Endocrine Diabetes fatigue syndrome (DFS)
If lifestyle, nutritional, and medical causes are ruled out, a targeted gluco-endocrine evaluation must be done to pinpoint the cause of DFS.
Diabetes-related causes include poor glycemic control, diabetic complications, and concomitant endocrinopathies. A suboptimal gluco-phenotype, involving any or all of the glycemic hexad (hyperglycemia, hypoglycemia, excessive glycemic variability), can lead to DFS.
Some evidence suggests that acute glycemic excursions are associated with fatigue. During an in-depth analysis of common hyperglycemic symptoms, 361 insulin-treated diabetics were asked to list their most common symptoms and report the blood glucose level at which those symptoms occurred. Tiredness was ranked fifth of the 16 most commonly reported symptoms. A mean symptom inventory score was computed for each subject based on the 16 symptoms. There was only a slight association between mean symptom inventory score and chronic glucose control measured by hemoglobin A1c (r = 0.149, p < 0.003). However 85% of the subjects were able to estimate a hyperglycemic threshold for the onset of their symptoms (including tiredness). The mean blood glucose threshold was 274 mg/dl, suggesting that acute elevations of blood glucose were more predictive of symptoms, including tiredness. Subjects also reported tiredness during lower levels of hyperglycemia, prior to osmotic symptoms such as thirst or increased urination.
Findings from an epidemiological study of 1,137 general practice patients with newly diagnosed type 2 diabetes revealed that fatigue was present in approximately 61% of patients at the time of diagnosis and was significantly associated with fasting plasma glucose (FPG) levels, but not hemoglobin A1c. It is possible that the average hemoglobin A1c may be falsely low in this group because their blood glucose level may not have been elevated the full three months. Similar findings were reported in 430 adults with newly diagnosed type 2 diabetes, prior to enrolling in the United Kingdom Prospective Diabetes Study (UKPDS). A high number of symptom complaints (including fatigue) was significantly associated with FPG, body mass index (BMI), and female gender. There was no association between symptom complaints and hemoglobin A1c, again suggesting a stronger association between fatigue and acute, rather than chronic, hyperglycemia.
Chronic hyperglycemia has long been assumed to cause fatigue; however, few data support this relationship. One cross-sectional study examined the relationship between glucose control and physical symptoms, moods, and well-being. The study included 188 Dutch patients with type 2 diabetes, and fatigue was measured using two different instruments: the Diabetes Symptom Checklist-Type 2 (DSC-Type 2) and the Profile of Mood States (POMS). Slight, but statistically significant, correlations between HbA1c and fatigue were noted using both instruments (DSC-Type 2 r = 0.14, p < 0.05; POMS r = 14, p < 0.05), suggesting that chronic hyperglycemia may contribute to fatigue.
In contrast, there was no association between hemoglobin A1c and fatigue symptoms as measured by the DSC-Type 2 during a two-year prospective study examining the initiation of insulin therapy in Dutch adults with type 2 diabetes. The authors reported a significant relationship of every unit increase of insulin dose with DSC-Type 2 total symptom complaint scores (which included a fatigue subscale) and POMS anger, displeasure, and fatigue scores, suggesting increased emotional fatigue possibly related to increased hypoglycemic events and the burden of daily injections.
In a study of patients with type 2 diabetes and restless leg syndrome, hemoglobin A1c was associated with sleepiness (as measured by the Epworth Sleepiness Scale), but not fatigue (as measured by the Fatigue Severity Scale).
Glucose variability may also cause psychological fatigue.
Similarly, fatigue may be the presenting symptom, or it may herald an insidious onset of vascular complications, such as heart failure and nephropathy. Lesser known comorbidities of diabetes, including chronic venous disease and Alzheimer’s disease, may also present with fatigue.
Persons with diabetes, especially type 1 diabetes, are more prone to endocrinopathy. Diseases such as hypothyroidism, Addison’s disease, Cushing‘s syndrome, and hypothyroidism, if left unrecognized and/or untreated, may worsen DFS. The symptoms, sign, and laboratory anomalies specific to these diseases, coupled with a high index of clinical suspicion, help in their identification.
At times, DFS may be iatrogenic. Drugs such as corticosteroids, beta blockers, diuretics, and statins are known to cause fatigue. Their use must be looked into during the evaluation of DFS.