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The Frustrated Patient With Diabetes

History and Examination

Maggie was 22 years old when she was initially diagnosed with type 2 diabetes (T2DM) during a routine physical examination. She had sought consultation for symptoms of fatigue and increased frequency of urination. These symptoms were becoming problematic for Maggie, both as a second-grade teacher and as a club soccer coach. Although she was shocked by the diagnosis, her primary care physician (PCP) suggested that she initiate metformin 500 mg twice daily with meals because her hemoglobin A1C (A1C) had already risen to 7.8%. Maggie was 7 lbs above her ideal body weight and her body mass index was 22 kg/m2. She attributed the 3-lbs weight gain over the previous month to “fatigue-induced inactivity.”

Family History
While in college, Maggie’s father was diagnosed with T2DM. He was treated with numerous pharmacologic agents, but “nothing seemed to work very well for him.” At age 62, Maggie’s father is currently on dialysis and takes multiple medications. “He is not doing well,” Maggie said. “I guess he never followed his doctor’s instructions very well. However, I hope this disease does not lead me down the same path as my Dad!”

Maggie’s mother is healthy and Maggie has no siblings. Apparently, Maggie’s paternal grandmother also had diabetes as well as several paternal aunts and uncles.

Laboratory Tests
The primary care provider (PCP) performs a battery of metabolic tests including a thyroid panel, basic metabolic panel, liver function test, hematology panel, urine microalbumin level, vitamin D level, and glutamic acid decarboxylase antibodies (to determine whether the patient has autoimmune diabetes). All of these tests are normal.

Maggie is advised to check her blood glucose levels fasting, before dinner, and 2 hours after dinner every day. Despite being adherent to the medication regimen and maintaining a strict exercise program by working out a minimum of 60 minutes daily, Maggie’s blood glucose levels are consistently elevated as shown in Figure 1.

Figure 1

This meter download record demonstrates consistently poor blood glucose control. Only a single reading is noted to be within the targeted range of 70 to 170 mg/dL. Peak glucose values are as high as 400 mg/dL.

A repeat point of service A1C performed after 6 weeks of metformin therapy was 8.9%. Maggie refused to initiate insulin without trying “at least one more oral agent.” Unfortunately, pioglitazone (Actos) resulted in a 7-lb weight gain associated with a rise in A1C to 9.6% at 6 months after she was initially diagnosed with diabetes.

Worsening Symptoms
Maggie was now becoming symptomatic, complaining of thirst, nocturia, blurry vision, and weight loss of 5 lbs over 4 weeks. Her PCP encouraged her to initiate basal insulin 10 units at 9 PM daily and self-titrate the dose by increasing the dose by 1 unit nightly until her fasting glucose levels achieved a target of <110 mg/dL. After 30 days, Maggie had noted no change in her fasting blood glucose levels despite increasing the dose of insulin from 10 units daily to 41 units daily. Clearly, Maggie was becoming more concerned, frustrated, and scared regarding the deterioration of her glycemic control. Table 1 lists the results of the physical examination and laboratory analysis performed at baseline and at 9 months after Maggie’s initial presentation.

Table 1


Diagnosis Options

Option 1
Screening Maggie for mental illness would be appropriate as 80% of patients with T2DM have had an episode of major depression within 5 years of their initial diagnosis of diabetes.1 Patients with any form of disabling mental illness will be unable to perform even the most basic self-management skills. Therefore, until their emotional status improves and their disabling mental capacity is stabilized, metabolic control of co-existing diabetes will be virtually impossible. Major depression, schizophrenia, and bipolar depression all increase the risk for diabetes and coronary artery disease. Because of the undeniable link between emotional unrest and diabetes, patients with mental illness should be screened for co-existing diabetes and vice versa. Treatment for patients with both mental illness and diabetes should focus first and foremost on improving the psychiatric illness with the use of appropriate pharmacologic and behavioral interventions. As one’s cognitive functioning improves, focus may be directed toward treating the metabolic parameters (weight, lipids, blood pressure, glycemic control) to individualized targets. By co-managing the mental and physical aspects of the disease state, long-term survivability will be enhanced.

Patients, such as Maggie, can be screened for mental illness using one of the rating scales shown in Figure 2. Maggie was administered the Patient Health Questionnaire-9, which showed no evidence of major depression or general anxiety disorder.

Figure 2

Option 2
Monogenetic diabetes—previously known as maturity onset diabetes of youth (MODY)—is a heterogeneous group of disorders, which result in β-cell dysfunction and affect approximately 2% of the hyperglycemic population. Often, these individuals are misdiagnosed as having either type 1 diabetes (T1DM) or T2DM. The diagnosis of monogenetic diabetes may be suspected in those individuals with a strong autosomal dominance penetrance of the disorder. Autosomal dominance implies that through generations, only one parent passes a specific genetic mutation to a child, which impairs normal β-cell function (Figure 3).2

Figure 3

Note the pattern of inheritance of diabetes in the 11 generations of this family. The genetic mutation from a single parent is required for a person to develop monogenetic diabetes. Whereas T2DM is of polygenic origin, MODY is an autosomal dominant single-gene phenotype of youth-onset diabetes occurring typically prior to age 25.

The genetic mutations that result in monogenetic diabetes appear to directly alter normal β-cell functioning. The six most commonly diagnosed forms of MODY are listed in Table 2. Each genetic mutation results in a different age of onset of hyperglycemia, pattern or severity of glucose intolerance, response to treatment, and extra-pancreatic manifestations. The typical clinical features of MODY patients are listed in Table 3.3

Table 2

Table 3

MODY 3 is the most common form of monogenetic diabetes in the United Kingdom, Europe, and Asia.4 Typically, MODY 3 patients present with diabetes as adolescents or in early adult life with progressive β-cell failure and increasing hyperglycemia. Due to the chronic and progressive nature of this disorder, these individuals are at high risk of microvascular and macrovascular complications similar to those patients with T2DM.4 Patients tend to have elevated, rather than low, levels of high-density lipoprotein cholesterol, which may be useful clinically in distinguishing them from patients with T2DM.3

MODY 3 patients are extremely sensitive to the hypoglycemic effects of sulfonylureas.5 Some patients who may have been erroneously diagnosed as having T1DM may be able to discontinue insulin after being placed on a sulfonylurea. Although some patients may maintain glycemic control for years with the use of a sulfonylurea, other patients may eventually require insulin intensification over time.3

Maggie learned about monogenetic diabetes through a regional conference she attended that was sponsored by the American Diabetes Association. After discussing the possible diagnosis with her PCP, all of her medications were discontinued and she was initiated on glimepiride (Amaryl) 4 mg at bedtime.

Option 3
Disturbed eating behavior is very common in young women with T1DM. Between 45% and 80% of teenage girls with T1DM are binge eaters, and up to 40% will eat while omitting insulin in an attempt to control their weight.6 Eating disorders are associated with many negative medical outcomes, including poor metabolic control, increased frequency of diabetes-related hospitalizations, and higher rates of diabetes-related complications, particularly retinopathy and perhaps neuropathy.6 Recently, researchers validated the utility of asking 5 questions to quickly and efficiently screen for an eating disorder (Table 4).7

Table 4

Maggie had a negative response to each of these screening questions. Thus, her PCP effectively ruled out an eating disorder.

Option 4
Although a psychological comorbidity has been ruled out as a cause of Maggie’s progressive hyperglycemic burden, could she be suffering from a condition known as diabetes distress (DD)? DD refers to the often hidden emotional burdens, stresses, and worries that are part of managing a chronic disease such as diabetes.8 The prevalence of DD is estimated to be as high as 45% in patients with T2DM.9 Patients with DD demonstrate poor glycemic control, diabetes self-management skills, and self-efficacy. Approximately 70% of high DD patients do not have clinical criteria for major depression.9

Certainly, Maggie is distressed over the lack of progress made towards improving her glycemic control. She is also gaining weight and becoming more symptomatic despite doing her absolute best at following the therapeutic regimen prescribed by her PCP. Could the diabetes distress that Maggie is feeling account for her metabolic deterioration?

Several options for treating DD have been evaluated in clinical trials. The ultimate goal is to achieve targeted metabolic control for patients who are on the verge of becoming nonadherent secondary to DD.10 Several of the strategies that may prove effective in managing patients with DD are shown in Table 5.

Table 5

Diabetes distress is highly responsive to intervention. Distress-specific interventions may be provided to patients, such as Maggie, in order to improve adherence, education, and diabetes self-management skills.

Selected Treatment

The correct diagnosis is "All of the Above." Genetic testing confirmed the diagnosis of MODY 3. Within 3 days of starting glimepiride 4 mg at bedtime, Maggie began to experience nocturnal hypoglycemia. The dose of glimepiride was reduced to 2 mg at bedtime. Within 2 months, Maggie’s A1C dropped from 9.8% to 6.5% and she is no longer a “frustrated patient.”

Updated on: February 6, 2014