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Back: Brittle Diabetes
“Does Your Patient Qualify as a 'Brittle' Diabetic?" 

Jeff Unger Picture


   Jeff Unger, MD
   PCMG Steering Committee Member
   Charlotte, North Carolina 
   Associate Director
   Unger Primary Care Medical Center and
   Catalina Research Institute
   Chino, Californina

Patients may be considered as having “brittle diabetes” if they experience frequent wide glycemic variability associated with episodes of hypoglycemia and diabetic ketoacidosis. These individuals, who defy all attempts at orthodox glycemic control, often regain consciousness in the emergency department after being treated for severe hypoglycemia. They often require repeated hospitalizations for diabetes related illnesses. Over time, they become a burden to society and third party payors while endangering their own safety often on a daily basis. Such patients can be challenging to themselves, their families, and their medical providers.

The real dilemma facing these patients, is determining the etiology of the brittle nature of their disease. Although not always apparent, a thoughtful clinician can often place their frustrations aside just long enough to understand the vary foundation from which these patients’ glycemic challenges tends to originate. If the cause is identified, medical costs will be reduced, families will become more stable and lives can be saved.

What are the primary causes of extreme glycemic variability? At the American Diabetes Association’s 55th Annual Postgraduate Course held in San Francisco this past February, Dr. Irl Hirsch facilitated a work shop on brittle diabetes. Many of the cases discussed at the workshop were not on my “A” list of disease states, yet warrant our attention nonetheless.

The following medical conditions should be considered as possible causes of “brittle diabetes”:

Celiac disease. The incidence of autoimmune celiac disease in patients with T1DM is approximately 15 %. [i] Although more common in children, adults with celiac disease may experience canker sores, osteoporosis, malabsorption, headaches and even miscarriages. Erratic glycemic control occurs due to the autoimmune destruction of the intestinal villi. This, in turn, results in both nutrients and medications to be unpredictably from the gut. One can diagnose celiac disease using serological testing or by performing a small bowel biopsy. However, serologic testing requires that patients have circulating levels of immunoglobulin A (IGA) and 5 % of all individuals have NO IGA. If one believes that celiac disease is a possible cause of brittle diabetes, simply suggesting initiating a gluten free diet might significantly improve the patient’s symptomatology and glycemic control within 2 weeks!

Lipodystrophy. Although considered a disorder of the past when pork and beef insulins were used to treat T1DM, lipodystrophy can still be seen today. Remember, insulin is a GROWTH HORMONE. The injection of a short acting insulin into the same site day after day, can cause fat accumulation to occur at the injection site resulting in lipodystrophy. Once lipodystrophy occurs, the absorption of the insulin from this particular injection depot will become impaired. Thus, any patient with brittle diabetes, especially those who are on an insulin pump, should have their injection sites inspected for lipodystrophy. If found, patients should find alternative sites to inject their insulin.

Mental illness
. Our patients with T1DM who are intensively managed typically take 4 injections of insulin daily. Prior to injecting they must check their blood glucose levels, carb count, adjust the dose of their premeal insulin based upon their insulin to carbohydrate ratio while factoring in their anticipated post absorptive activity level. In addition, these patients must take 1 or 2 cholesterol lowering medications, 2-3 antihypertensive agents and an aspirin. They must keep their appointments with their primary care physician, see their specialty doctors, exercise daily, remember to get their flu vaccine every year and get their prescriptions filled on a timely basis. When they get to their appointments, they will be asked to present their blood glucose logs or their glucose meter for downloading and assist the physician in interpreting the numbers. So, you think this is difficult? How can someone possibly do all of this successfully if they see spiders crawling on the wall or hear voices telling them to “kill a family member?” Patients with mental illness have an inherent high risk of developing metabolic disorders such as cardiovascular disease, obesity, hypertension, hyperlipidemia and type 2 diabetes
[ii] Patients with brittle diabetes should be screened for mental illness (major depression, bipolar disorder and schizophrenia). Any patient with mental illness should have their emotional disorders fixed FIRST before attempting to improve glycemic control. Partnering with a mental health provider may be necessary in some cases of treatment resistant depression.


Canabus hyperemisis syndrome. Gastroparesis is a known cause of erratic glycemic control. Ideally, exogenous insulin injections should be timed to correspond with the anticipated rise in blood glucose following a meal time nutrient bolus. In prediabetes, gastric emptying is often very rapid, implying that postprandial glucose levels rise very high causing the pancreatic beta cells to become “over worked” and “burned out.” However, later in the course of diabetes, especially when one is exposed to chronic hyperglycemia, gastric emptying is delayed. Insulin given 15 minutes prior to a meal may result in immediate postabsorptive hypoglycemia (because the nutrients have yet to be absorbed from the small intestines) and delayed hyperglycemia, because serum insulin levels fall as nutrient absorption from the gut finally occurs. Hyperglycemia further slows gastric emptying. However, T1DM patients who abuse marijuana may develop severe gastroparesis because this drug also slows gastric emptying. The typical clinical presentation would be a patient in their 20’s who does fairly well with glycemic control during the week. However, if they smoke marijuana heavily on weekends they would develop severe gastroparesis resulting in vomiting, dehydration and diabetic ketoacidosis. Urine drug screening should be done for anyone suspected of having this disorder[iii].

Patient insists they are adherent to insulin regimen, yet A1C is > 12 %. Anyone with an A1C > 12 % who is on an insulin regimen is omitting injections. If the patient is insistent that they are in fact using insulin as directed, one can perform a simple in-office test. Obtain a pre-test blood glucose and insulin level in the office prior to watching the patient self-administer their own insulin. Two hours later, draw a 2nd insulin and blood glucose level. The second values should demonstrate a rise in insulin levels and a lowering in the patient’s blood glucose. If insulin levels do not rise and glucose levels increase, the patient may actually have developed insulin antibodies. These individual should be referred to a diabetes specialist for further evaluation.

Determining the cause of brittle diabetes requires the clinician to have insight into the patient’s character and personal life. In some cases of organic disease there may be complex interactions between the pathologic and the intellectual processes which must be considered.

Jeff Unger, MD

How are you treating your diabetes patients who may be considered as being brittle? Let's discuss together on PCMG's Blog so we may find a more efficacious means by which they could be managed.


[i] Holmes GK. Screening for coeliac disease in type 1 diabetes. Arch Dis Child. 2002;87:495-498.

[ii] Managing mental illness in patients with diabetes.  In: Unger Jeff. Diabetes Management in Primary Care. Lippincott, Williams and Wilkins.  Philadelphia, PA. 2007. P. 647-682

[iii] Crowley TJ, MacDonald MJ, Whitmore EA, et al. Cannabis dependence, withdrawal and reinforcing effects amongst adolescents with conduct symptoms and substance use disorders. Drug Alcohol Depend 1998;50:27–37