Diabetes Mellitus & Insulinoma- 3 - Free MCQ Practice Test with solutions,

Autoimmune markers for newly diagnosed type 1 diabetes mellitus

1. ICA antibody
2. Glutamic Acid Decarboxylase (GAD65)
3. Insulin islet cell antibody
4. Tyrosine phosphatase
5. Zinc transporter 8

• HNF- 1β gene is involved in pathogenesis of MODY5.
• HNF- 1α gene is involved in pathogenesis of MODY 3.
• Most common type of MODY is MODY 3.

• Type 1 diabetes has insulinopenia due to reduced β cell mass
• Latent autoimmune diabetes in adults is a variant of type 1 diabetes mellitus
• MODY has impaired glucose induced insulin release due to autosomal dominant pattern of inheritance. The beta cell mass is normal. It involves mutations in nuclear transcription factor that regulates islet gene expression.
• Wolfram syndrome is an autosomal recessive condition neurodegenerative disorder leading to diabetes mellitus, diabetes insipidus, optic atrophy and deafness.

• In cirrhosis, blood sugar is elevated, due to reduced uptake of sugar by liver
• In myotonic dystrophy and lipodystrophy, there is tissue insensitivity to insulin leading to hyperglycemia.
• Sarcoma especially large retroperitoneal sarcomas secrete IGF-2 and lead to hypoglycaemia.

GLP-1 Receptor agonists: exenatide, albiglutide, dulaglutide are available as once weekly administration by subcutaneous route. Liraglutide needs to be given once per day.

Traditionally long acting insulins could not be mixed with short acting insulins due to different pH.
However insulin degludec preparation is now available as 70% insulin degludec and 30% insulin aspart and is injected once or twice per day.

The most common cause of death in type 1 diabetes mellitus is end stage chronic kidney disease. In contrast in type 2 Diabetes mellitus macrovascular disease is more common leading to myocardial infarction and stroke.

The image shows an insulin pump which is appropriate for patients with type 1 diabetes who are motivated, mechanically inclined and educated about the disease.
The device shown is tubeless and delivers subcutaneous basal and bolus insulin from a wireless personal digital assistant.
Continuous subcutaneous insulin Infusion pump

The most common cause of death in type 1 diabetes mellitus is end stage chronic kidney disease. In contrast in type 2 Diabetes mellitus macrovascular disease is more common leading to myocardial infarction and stroke.

• There is reduced tissue sensitivity to insulin between 5 am to 8 am which leads to Pre-breakfast Hyperglycemia and is known as Dawn Phenomenon.
• Dawn phenomenon is found in 75% of Type 1 diabetes mellitus patients and can aggravate the hyperglycemia.

Pre-breakfast Hyperglycemia: Classification by Blood Glucose
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The case given is of high anion gap metabolic acidosis with increased serum lactate and negative ketones. This rules out choice B and C
Lactic acidosis of type A variety occurs due to poor tissue perfusion and occurs due to

1. Shock or cardiac failure
2. Severe Anaemia
3. Mitochondrial enzyme defects
4. Carbon monoxide poisoning, Cyanide poisoning

Lactic acidosis of type B occurs due to

1. Malignancies
2. Diabetes mellitus
3. Renal or hepatic failure
4. Thiamine deficiency
5. Severe Infections (Cholera, Malaria)
6. Seizures
7. Drugs/toxins (biguonides, ethonol, methanol, propylene glycol, Isoniazld, and fructose and Nucleoside analogue reverse transcriptase inhibitors In HIV and linezolld).

• For any trauma patient or any emergency, Airway is to be secured 1st.
• CT scan to rule out Intracranial bleed
• A diabetic patient found unconscious, always rule out hypoglycaemia

• Prolonged hypoglycemia can damage the blood brain barrier and leads to cerebral edema.
• This also explains hemiplegia seen in hypoglycemic patients sometimes.
• Post ictal state is seen after hypoglycemic seizures.

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Islet cell transplantation involves the extraction of islets of Langerhans from organ donors through a complex purification process. These are the cells responsible for the production of insulin. These cells are then injected into the recipient, usually into the portal vein. They then engraft into the parenchyma of the liver and secrete insulin.

Whipple’s triad is based on three criteria on which hyper-insulinism is due to pancreatic islet-cell disease is diagnosed:

1. Neuromuscular signs with fasting or exercise
2. Low blood glucose levels associated with clinical signs
3. Reversal of clinical signs with the administration of glucose.

Whipple’s operation: Carcinoma pancreas
Whipples disease: Malabsorption caused by Trophyerma Whipelli

• Since the age of the patient is 50 years, it is highly likely that the patient has type II diabetes mellitus, which is insidious in onset. Hence though patient has no ocular complaints the fundus examination for retina evaluation should be done immediately.
• The significance of this problem is highlighted by the finding that individuals with DM are 25 times more likely to become legally blind than individuals without DM.
• Blindness is primarily the result of progressive diabetic retinopathy and clinically significant macular edema.

• Glycosylated haemoglobin is not a reliable test in patients with hemoglobinopathies like thalassemia and sickle cell anemia.
• It is an excellent test indicating poor glycemic control in diabetics and higher values are associated with microvascular complications.
• It is a retrospective test indicating glycemic control for 8-12 weeks

Genetic defects of pancreatic cell function

For PETs in the pancreas, EUS is highly sensitive, localizing 77-100% of insulinomas, which occur almost exclusively within the pancreas.
Tests for location of pNET:

1. Somatostatin Receptor Scintigraphy is the initial imaging modality but is less available.
2. Helical CT scan has a sensitivity of 80%
3. Gadolinium based MRI has sensitivity of 85%
4. If above scans are negative, then Endoscopic ultrasound will be able to pick up the insulinoma which is usually <1,5 cm in size, with 90% sensitivity
5. If all the above tests turn negative then calcium stimulated angiography can be used to localise the tumour.
6. The intra-arterial calcium test also allows differentiation of the cause of the hypoglycaemia and indicates whether it is due to an insulinoma or a nesidioblastosis.

Obese patient age 45 years with presentation of diabetic ketoacidosis points to hyperglycemia.
Usually in DKA the value of blood sugar is around 300 mg%.

The basic principles of sulfonylurea metabolism can be summarized as follows:

• Chlorpropamide is eliminated almost exclusively by the kidney.
• Glyburide has weak active metabolites that are excreted in the urine and accumulate in patients with impaired kidney function.
• Glipizide and tolbutamide are metabolized by the liver and primarily excreted in the urine as inactive metabolites.

However, each has one metabolite that may have weak hypoglycemic activity.

• Diabetics have accelerated atherosclerosis due to which they have 3 times more chances of MI as compared to nondiabetics
• The future development of autonomic neuro-pathy will mask findings of MI like chest pain and sweating leading to silent MI and this patient has only symptoms of dizziness  which is due to decreased Cardiac output due to the silent / painless MI developed in this patient
• In inferior wall MI, the blockage of Right coronary artery leads to less supply to SAN (SA nodal artery ischemia) and leads to bradycardia severe enough to warrant a Temporary pacemaker insertion.

Among patients who are treated with insulin, the starting dose of insulin may need to be lower than would ordinarily be used for patients with normal kidney function.
Guidelines for adjustment of dose of insulin in patient of ESRD

• No dose adjustment is required if the GFR is > 50 mL/min.
• The insulin dose should be reduced to approximately 75 percent of baseline when the GFR is between 10 and 50 mL/min
• The dose should be reduced by as much as 50 percent when the GFR is < 10 mL/min

IV insulin should be continued until the acidosis resolves and the patient is metabolically stable. As the acidosis and insulin resistance associated with DKA resolve, the insulin infusion rate can be decreased (to 0.05-0.1 units/kg per hour).

• Ketoacidosis begins to resolve as insulin reduces lipolysis, increases peripheral ketone body use, suppresses hepatic ketone body formation, and promotes bicarbonate regeneration. However, the acidosis and ketosis resolve more slowly than hyperglycemia.
• Soda-bicarbonate has no role in management of DKA
• I.V. fluids correct the water deficit and sodium deficit primarily.

The Diabetes Complications and Control Trial demonstrated that improvement of glycemic control reduced

• Non proliferative and proliferative retinopathy (47% reduction)
• Micro-albuminuria (39% reduction), clinical nephropathy (54% reduction),
• Neuropathy (60% reduction).

The results of the DCCT predicted that individuals in the intensive diabetes management group would gain 7.7 additional years of vision, 5.8 additional years free from ESRD, and 5,6 years free from lower extremity amputations. If all complications of DM were combined, individuals in the intensive diabetes management group would experience 15.3 more years of life without significant microvascular or neurologic complications of DM, compared to individuals who received standard therapy.

• Choice A: Amyotrophy is an alternative term for lumbosacral plexopathy seen in diabetics and associated with pain in thigh and quadriceps wasting. Good sugar control reduces nerve damage
• Choice B. Good sugar control reduces nerve damage.
• Choice C. fluoroscein dye leakage implies macular edema and one it is developed then moderate visual loss will occur. The point is that the damage already has been done and good sugar control does not change angiography findings once they are developed. Also remember that macular edema causes visual loss while blindness in diabetics is due to vitreous haemorrhage and tractional retinal detachment, Good sugar control reduces neovascularization and will reduce retinal detachment chances but not Dye leakage on FFA.
• Choice D. Progression to ESRD is reduced by good sugar control.

• Congenital malformations are not seen in gestational diabetes as it develops by second trimester when the organogenesis has occurred already.
• Congenital malformations are seen in babies born to mothers with pre-existing uncontrolled diabetes mellitus
• Metformin has been shown to be as effective and having better compliance as compared to insulin in management of gestational diabetes mellitus.

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• In current edition of Harrison, albuminuria term is used and microalbuminuria has been removed. Albuminuria in a spot sample is defined as urinary albumin to creatinine ratio of > (30mg/g) creatinine.

Tight glycemic control improves the micro-vascular complications but has no effect on macrovascular complications.
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• Necrobiosis lipoidica is a necrotising skin condition that usually occurs in patients with diabetes but can also be associated with Rheumatoid Arthritis.
• It is a disorder of collagen degeneration with a granulomatous response, thickening of blood vessel walls, and fat deposition. The main complication of the disease is ulceration, usually occurring after trauma. Infections can occur but are uncommon.