Brittle Diabetes Mellitus: Definition and Management
Definition
Brittle diabetes is characterized by severe, unpredictable glycemic instability with erratic swings between hypoglycemia and hyperglycemia that disrupt daily life and persist despite optimized insulin therapy. 1, 2
The condition manifests as chaotic blood glucose profiles with greater and more unpredictable variation than typical diabetes, leading to frequent hospitalizations for diabetic ketoacidosis (DKA) or severe hypoglycemia. 1, 2
Brittleness affects approximately 3 per 1,000 insulin-dependent patients, predominantly young women, though distinct patterns occur across different life stages. 2, 3
In type 3c diabetes (pancreatogenic diabetes from chronic pancreatitis), reduced glucagon secretion and pancreatic polypeptide deficiency contribute to characteristically brittle control with erratic glucose swings. 4
Quality of life is dramatically compromised, with premature chronic complications, lower quality-of-life scores, more microvascular complications, and shortened life expectancy. 1, 2
Diagnostic Approach
Always identify the specific underlying etiology—brittle diabetes is never idiopathic and requires systematic evaluation to direct appropriate therapy. 5, 6
Quantify instability using continuous glucose monitoring or validated metrics such as Mean Amplitude of Glycemic Excursions (MAGE), Lability Index, or Clarke's score for hypoglycemia awareness. 2
Perform insulin challenge testing (0.1 U/kg subcutaneously and intravenously) to distinguish subcutaneous insulin resistance, intravascular resistance, or peripheral tissue resistance. 6
If insulin response is normal, complete comprehensive psychosocial evaluation including psycholinguistic testing, assessment for eating disorders (especially bulimia), depression, manipulative behavior, and factitious disease. 3, 5, 6
Assess gastric motility, as delayed gastric emptying from autonomic neuropathy is a major organic cause of brittleness. 2
Evaluate counterregulatory hormones (glucocorticoid, glucagon), malabsorption syndromes, and medications that affect glucose metabolism (alcohol, antipsychotics). 2
Screen for underlying medical conditions disrupting insulin sensitivity or glucose utilization. 3
Management Algorithm
Stage 1: Structured Education and Optimization
All patients with brittle diabetes must undergo intensive, hypoglycemia-specific structured education programs with frequent contact. 4
Implement rigorous hypoglycemia avoidance strategies: never delay treatment of low glucose, recognize high-risk times, detect subtle symptoms, and confirm readings through frequent self-monitoring. 4
Programs such as Blood Glucose Awareness Training (BGAT) or Dose Adjustment For Normal Eating (DAFNE) reduce severe hypoglycemia episodes by 50% even in patients with long-standing diabetes (>15 years) and impaired awareness. 4
Weekly telephone contact and monthly face-to-face visits with specialized teams are essential—intensive provider contact is the most effective intervention. 4
Optimize insulin therapy using rapid-acting analogs (aspart, glulisine, lispro) which reduce severe hypoglycemia by 20% and nocturnal hypoglycemia by 45% compared to regular insulin. 4
Switch to basal analogs (glargine, detemir, degludec) which reduce severe hypoglycemia by 27% and nocturnal hypoglycemia by 31% compared to NPH insulin. 4
For type 3c diabetes specifically, implement individualized medical nutrition therapy with regular glucose monitoring, alcohol avoidance to prevent hypoglycemia, and patient-specific meal plans to reduce hyperglycemic excursions. 4
Reassess glycemic and hypoglycemia targets every 3–6 months, individualizing goals based on patient circumstances. 4
Stage 2: Add Single Diabetes Technology
If brittleness persists after 3–6 months of optimized education, add either continuous subcutaneous insulin infusion (CSII) or continuous glucose monitoring (CGM). 4
CSII (insulin pump) provides a fourfold reduction in severe hypoglycemia and 0.6% improvement in HbA1c, with greater benefit in older patients and those with more frequent severe hypoglycemia. 4
Real-time CGM combined with standardized education reduces severe hypoglycemia from 8.9 to 0.8 episodes per patient annually in high-risk patients. 4
Small studies show CSII restores hypoglycemia awareness in 84% of patients with impaired awareness at 1 year. 4
Stage 3: Sensor-Augmented Pump with Low-Glucose Suspend
For patients with continued problematic hypoglycemia despite education and one technology, implement sensor-augmented insulin pumps with automated low-glucose suspend features. 4
This combination provides superior protection against severe hypoglycemia compared to either technology alone. 4
Maintain very frequent contact with a specialized hypoglycemia service during this stage. 4
Stage 4: Transplantation
Consider islet or pancreas transplantation for patients whose life-disrupting brittleness persists despite maximal medical therapy. 4
Islet transplantation achieves complete resolution of severe hypoglycemia in 85% of patients and significant reductions in the remaining 15%, with 82% achieving HbA1c <7% without severe hypoglycemia at 1 year. 4
At 2 years, 70% maintain insulin independence with mean HbA1c improvement from 6.5% to 6.2% and severe hypoglycemia reduction from 20 episodes/year to 0.3 episodes/year. 4
Islet transplantation is particularly appropriate for patients with hypoglycemia unawareness, BMI <25, normal renal function, and no immediate pregnancy plans (due to immunosuppression requirements). 2
Implantable pumps are alternatives for patients weighing >80 kg or with renal/hepatic dysfunction. 2
Etiology-Specific Interventions
Direct therapy at the identified underlying cause—approximately 50% of brittle patients respond to specific etiologic treatment. 5
Psychosocial Causes (Most Common)
Psychiatric conditions (bulimia, depression) require specific psychiatric therapy and are treatable. 3, 5
Factitious disease and manipulative behavior necessitate psychological interventions, though these remain therapeutically challenging. 5
Organic Causes
Treat malabsorption syndromes and discontinue causative medications. 2
Address delayed gastric emptying from autonomic neuropathy with prokinetic agents. 2
Correct deficiencies in counterregulatory hormones when identified. 2
Geriatric Type 1 Diabetes (Largest Group)
This population develops brittleness from frailty, chronic renal failure, dementia, vision loss, loss of counterregulation, and diseases of aging leading to unintentional insulin omission and dosing errors. 3
Simplify regimens, increase monitoring frequency, involve caregivers, and liberalize glycemic targets to prevent hypoglycemia. 3
Elderly patients have higher hypoglycemia risk due to renal impairment, malnutrition, and blunted counterregulatory responses. 7
Insulin Access and Food Insecurity
- Address socioeconomic barriers to insulin access and food security, now seen worldwide. 3
Hospital Management Considerations
In hospitalized brittle patients, multiple risk factors for hypoglycemia coexist beyond baseline instability. 4
Triggers include altered nutritional state, sudden corticosteroid dose reduction, new NPO status, inappropriate insulin timing relative to meals, reduction in intravenous dextrose rate, and interruption of enteral/parenteral nutrition. 4
Use basal-bolus insulin therapy rather than sliding-scale insulin alone—this achieves target glucose <140 mg/dL in 68% versus 38% with sliding scale. 4
For glucocorticoid-induced hyperglycemia, administer NPH insulin concomitantly with steroids (peaks at 4–6 hours) in addition to basal-bolus regimens. 4
Critical Pitfalls to Avoid
Never assume brittleness is untreatable—there is always a specific, identifiable etiology requiring systematic evaluation. 5
Avoid empirical therapy and invasive procedures without identifying the underlying cause. 5
Do not discontinue basal insulin in type 1 diabetes even during hypoglycemia—cessation rapidly precipitates ketoacidosis; instead, modestly reduce the dose while maintaining continuous coverage. 7
Recognize that only 50% of brittle patients respond to specific etiologic treatment, necessitating escalation through the staged algorithm. 5
Avoid overly aggressive glucose lowering—balance control against hypoglycemia risk, particularly in elderly or critically ill patients. 7
Refer patients to specialized diabetes centers with expertise in brittle diabetes when initial evaluation and management fail. 5