Definitions of Diabetes Subtypes
Brittle Diabetes
Brittle diabetes is a rare, severe form of Type 1 diabetes characterized by life-disrupting glycemic instability with unpredictable, frequent episodes of hypoglycemia and/or diabetic ketoacidosis that persist despite intensive, closely supervised insulin therapy. 1, 2
- Affects approximately 3 per 1,000 insulin-dependent patients, predominantly young women 1
- Defined by metabolic instability that cannot be attributed to management failure and results in recurrent/prolonged hospitalizations 2
- Patients demonstrate chaotic glycemic profiles with greater and more unpredictable variation than "stable" diabetic patients 2
Clinical Manifestations
Three distinct forms exist 1:
- Recurrent diabetic ketoacidosis - repeated episodes requiring hospitalization
- Predominant hypoglycemic forms - severe, unpredictable hypoglycemia
- Mixed instability - combination of both patterns
Underlying Etiologies
There is always a specific, identifiable etiology causing brittle diabetes, though it may require extensive metabolic and psychological testing to uncover. 3
The most common causes include 1, 3, 4:
- Psychosocial factors - most frequent etiology, including manipulative behavior, factitious disease, bulimia, and depression 3, 5
- Gastroparesis from autonomic neuropathy causing delayed gastric emptying 1
- Malabsorption syndromes affecting insulin or nutrient absorption 1
- Defective insulin absorption or degradation at subcutaneous sites 1, 4
- Counterregulatory hormone defects, particularly glucocorticoid and glucagon deficiency 1
- Systemic insulin resistance at peripheral tissues 4
Modern Reconceptualization
Recent evidence redefines brittle diabetes as occurring in four distinct life stages, each with specific characteristics and reversible factors 5:
- Younger patients with psychiatric comorbidities - bulimia, depression requiring specific psychiatric therapy 5
- Patients with underlying medical conditions - diseases disrupting insulin sensitivity or glucose utilization 5
- Geriatric Type 1 diabetes (largest group) - frailty, chronic renal failure, dementia, vision loss, loss of counterregulation, unintentional insulin omission, and increasing insulin sensitivity 5
- Insulin access/food insecurity - lack of consistent insulin supply and nutrition 5
Diagnostic Approach
An algorithmic diagnostic approach is essential, centered on glucose response to standardized insulin challenges (0.1 U/kg subcutaneously and intravenously). 4
- If insulin response is normal: complete psychosocial evaluations including psycholinguistic and health psychological testing, assess gastric motility, counterregulatory hormones, and patient compliance 4
- If insulin response is abnormal: identify location of insulin resistance (subcutaneous, intravascular, or peripheral tissue) 4
- This approach successfully identifies etiology in 97% of cases (29 of 30 patients in validation study) 4
Prognosis and Management Principles
- Poor prognosis with lower quality of life scores, increased microvascular complications, pregnancy complications, and shortened life expectancy 1
- Approximately 50% of brittle diabetic patients respond to specific etiologic treatment 3
- Empirical therapy and invasive procedures are contraindicated - therapy must be directed at the underlying pathogenic factor 3
- Requires multidisciplinary team approach involving broad range of disciplines 2
- For refractory cases with hypoglycemic unawareness: consider isolated islet transplantation if BMI <25 and normal renal function 1
- For patients >80 kg or with renal/hepatic dysfunction: implantable pumps may be advantageous 1
Double Diabetes
The provided evidence does not contain information defining or describing "double diabetes." This term typically refers to Type 1 diabetes patients who develop insulin resistance characteristic of Type 2 diabetes, but no guideline or research evidence was provided addressing this entity.
Idiopathic Diabetes
The provided evidence does not contain information defining or describing "idiopathic diabetes." This term historically referred to diabetes without identifiable cause, but no specific guideline or research evidence was provided addressing this classification.
Immunological Diabetes
Type 1 diabetes is defined by the presence of one or more autoimmune markers and accounts for approximately 5% of diabetes cases. 6
- Characterized by autoimmune destruction of pancreatic beta cells 6
- Requires insulin therapy from diagnosis with multiple-dose insulin injections or continuous subcutaneous insulin infusion 7, 6
- Insulin analogues should be used to reduce hypoglycemia risk 7, 6
- Patients should receive education on matching prandial insulin doses to carbohydrate intake, preprandial blood glucose levels, and anticipated activity 7
The term "immunological diabetes" is not a standard classification in current diabetes guidelines, but Type 1 diabetes represents the primary form of autoimmune/immunological diabetes mellitus.