Appoach To Brittle Diabetes: Clinical Algorithm To Determine The Etiology

C H A P T E R
Appoach to Brittle Diabetes
162 Seetha Raju
INTRODUCTION CLINICAL ALGORITHM TO DETERMINE THE ETIOLOGY

Brittle diabetes is defined as severe instability of blood The diagnostic algorithm was the glucose response
glucose levels with frequent and unpredictable episodes to 0.1 unit / kg insulin administered subcutaneously
of hypoglycaemia or ketoacidosis that disrupts day to and intravenously. If this response was ’’normal’’ then
day life. Almost all diabetics experience swings of blood psycosocial evaluations were completed, including
sugar which are less predictable and greater than in non psycolinguistic and health psycological testing.Then
diabetics. Brittle diabetes is uncommon (less than 1% of other parameters affecting blood glucose concentration
insulin taking population) and it causes a huge burden eg. gastric motility, counter regulatory hormones, coeliac
on the patient due to multiple hospital admissions. It disease, hypothyroidism, adrenal insufficiency, insulin
is episodic and almost always related to stressful life autoantibodies and most importantly patients compliance
situations. It affects 3/1000 insulin dependent diabetic with prescribed regimens were assessed. If the response
patients mainly young women. Its prognosis is poor were ‘’abnormal’’ the location of the insulin resistance
with lower quality of life scores, more microvascular and was identified as being subcutaneous, intravascular or at
pregnancy complications and shortened life expectancy. the peripheral tissue.
CAUSES OF BRITTLE DIABETES EVALUATION AND DIAGNOSIS

Main causes includes A careful evaluation should be performed in patients
• Non physiologic matching of meals/exercise and with brittle diabetes. A detailed history as to the duration
insulin administration. of diabetes, description of episodes of DK, severe
hypos, presence of diabetic complications (particularly
• Malabsorption autonomic neuropathy) and prescribed insulin regimens
• Certain Drugs (alcohol, antipsycotics) should be taken. It should also be determined if there
was a period of stable diabetes preceeding the brittleness
• Defective insulin absorption or degradation
and what happened in the patient’s life circumstances
• Defect of hyperglycaemic hormones especially coincident with the onset of brittleness. Psycosocial factors
glucocorticoid and glucagon. need to be assessed. For patients with recurrent episodes
of DK, a possible chronic cryptic infection (sinusitis,
• Delayed gastric emptying as a result of autonomic
osteomyelitis, renal or perirenal abscess and lung abscess)
neuropathy.
should be excluded. For all patients a diabetic educational
• Psycosocial factors are very important and assessment is useful to evaluate whether the patients
factitious brittleness may lead to a self perpetuating knows how to manage diabetes and rule out diabetes
condition. This is because of patient centred mismanagement (factitious brittle diabetes ). In this case a
behavioral issues. Some of these problems may “in hospital” assessment and management of blood sugar
be short lived and related to a stressful situation is necessary.
(unhappiness at school or home).
Iatrogenic hypoglycaemia is the result of the interplay
CLINICAL MANIFESTATIONS of absolute or relative therapeutic insulin excess and
Patients have wide swings of blood sugar levels and compromised physiological and behavioural defences
report differing blood sugar responses to the same dose against falling plasma glucose concentrations in type 1
and type of insulin. Most patients are in their twenties diabetes in type 1 diabetes mellitus (T1DM) and advanced
or thirties. Their glycated haemoglobin (HbA1c) are type 2 diabetes mellitus (T2DM). Courtesy of Dr. Philip
typically elevated (10-14%) and acute complications (DK Cryer.
and hypo) and chronic microvascular complications are
commoner (67% versus 25%). Brittle diabetics also had a
MANAGEMENT
lower quality of life score. The age of death ranges from Brittle diabetes is difficult to treat
27-45 years with a predominance in young women. Those General principle
who survived had resolution of brittleness, but suffered a • Patients to be instructed how to match the insulin
significant complication burden. Frequent hypoglycaemia dose to the amount of carbohydrates ingested.
even if asymptomatic causes both defective glucose • Insulin regimens must be individually tailored to
counter regulation and hypoglycaemia unawareness and reduce the risk of hypoglycaemia while matching
thus a viscious cycle of recurrent hypoglycaemia.
756
Table 1: Counterregulatory response to hypoglycaemia
Condition Glucose Insulin Glucagon Epinephrine
Nondiabetic Decreases Increases Increases
T1DM No Decrease* No Increase Attenuated Increase*
T2DM
Early Decreases Increases Increases
Late(Absolute endogenous No Decrease* No Increase Attenuated Increase*

insulin deficient)
DIABETES
glycaemic control. The use of insulin analogues or clinician error in management, other causes
with ultrafast or ultraslow action and use of being psycosocial, malabsorbtion, delayed gastric
subcutaneous insulin pumps are effective in brittle emptying, systemic insulin resistance.
diabetes.
• The treatment includes diabetes education,
• SMBG is an excellent tool for the patients and a intensive insulin therapy with frequent or
motivated patient can use this tool to manage his continuous glucose monitoring and constant
blood sugars. interaction between patient and the clinician.
Psycotherapy is advocated in selected patients.
• CGM (Continuous glucose monitoring) may
further facilitate the understanding of glycaemic REFERENCES
variability. 1. David K McCullrch. M.D.David M.Nathan. M.D.Jean E
Mulder M.D. - The adult patient win diabetes mellitus Up
• Sensor augmented insulin pumps (an insulin To Date June 2015.
pump with a CGM device) improves glycemic
2. Cartwright A, Wallymahmed M, Macfarlaane IA, et al. The
control without hypoglycaemia. outcome of brittle type 1 diabetes –a 20 year study QJM
• Fully automated closed loop systems of insulin 2011; 104:575.
delivery based on CGM sensing (bionic pancreases) 3. Vantyghem MC,press M.management strategies for brittle
are available. This device also integrates glucagon diabetes. Ann Endocrinol (Paris) 2006; 67:287.
delivery. 4. Clar C, Barnard K, Cummins E, et al. Self – monitoring of
blood glucose in type 2 diabetes; systematic review Health
• Islet cell transplantation –an effective therapeutic Technol Assess 2010; 14:1.
option entailing good expected outcomes. The
5. Polonsky WH, Fisher L, Schikman CH, et al. Structured
limiting factor is the effect of immunosuppressive self-monitoring of blood glucose significantly reduces
therapy and recurrence of autoimmunity. A1C levels in poorly controlled, noninsulin-treated type
2 diabetes : results from the structured Testing Program
SPECIAL SITUATIONS study. Diabetes Care 2011; 34:262.
• Hypoglycaemia unawareness A 2-3 Week period
6. Gandhi GY, Kovalaske M, Kudva Y, et al. Effcacy of
of scrupulous avoidance of hypoglycaemia is
continuous glucose monitoring in improving glycemic
advisable since that often restores awareness (Table control and reduceing hypoglycemia :a systematic review
1). and meta – analysis of randomized trials. J Diabetes Sci
• Gastroparesis – promotility agents improved Technol 2011; 5:952.
gastric enptying and relieved the symptoms of 7. Szypowska A, Ramotowska A, Dzygalo K, Golocki D.
gastroparesis but did not help with metabolic Beneficial effect of real-time countious glucose monitoring
system on gycemic control in type 1 diabetic patients:
control.
systemic review and meta-analysis of randomized trials.
• Psycosocial – Psycotherapy may help in selected Eur J Endocrinol 2012; 166:567.
patients. 8. Yeh HC, Brown TT, Maruthur N, et al. Comparative
effectiveness and safety of insulin delivery and glucose
SUMMARY AND RECOMMENDATIONS monitoring for diabetes mellitus : a systematic review and
• Brittle diabetes in defined as severe instability meta-analysis. Ann Intern Med 2012; 157:336.
of blood glucose levels with frequent and 9. Juvenile Diabetes Research Foundation Continuous glucose
unpredictable episodes of hypoglycaemia or monitoring study Group, Beck RW, Buckingham B, et al.
ketoacidosis. Factors predictive of use and of benefit from continuous
glucose monitoring in type 1 diabetes. Diabetescare 2009;
• The diagnosis is established when a patient with 32:1947.
absolute insulin deficiency (type 1 or type 2) has
10. Ritholz MD, Atakov-Castillo A, Beste M, et al. Psychosocial
frequent episodes of hyper or hypoglycaemia.
factors associated with use of continuous glucose
• The major cause of brittle diabetes is patient monitoring. Diabet Med 2010; 27:1060.

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C H A P T E R

Appoach to Brittle Diabetes

162 Seetha Raju

INTRODUCTION CLINICAL ALGORITHM TO DETERMINE THE ETIOLOGY

CAUSES OF BRITTLE DIABETES EVALUATION AND DIAGNOSIS

T1DM No Decrease* No Increase Attenuated Increase*

Late(Absolute endogenous No Decrease* No Increase Attenuated Increase*

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