Test: Diabetes Mellitus & Insulinoma- 1 - NEET PG MCQ

• Sitagliptin is ruled out as DPP-4 inhibitors are associated with risk of pancreatitis
• Liraglutide is ruled out since it is available in injectable format and patient has refused to take injections.
• Pioglitazone has black box warning due to risk of bladder cancer.
• Canagliflozin will be the most suitable for the patient since it will help in reducing the weight of the patient as well.

• Metformin should be discontinued in following settings in diabetics and insulin is used:
  • Hospitalized patients
  • Can't take orally
  • Receiving Radiographic contrast material
• Metformin is excreted via the kidney and is contraindicated if GFR < 60ml/min/1.73 m2 BSA, level of serum creatinine is > 1.4 mg/dl in women and > 1.5mg/dl in men.
• If metformin is erroneously prescribed, it would result in development of lactic acidosis in the patient.

Types of diabetes mellitus

HbA1C values are affected by conditions that affect RBC survival or mean erythrocyte age.
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• The patient is already diabetic at the time of conception. Since organogenesis occurs in first trimester, it is imperative to achieve good sugar control in T1. Hence serum fructosamine is recommended, because it accurately describes glycaemic control retrospectively for previous 1-2 weeks.
• Glycosylated haemoglobin gives information about retrospective control of diabetes mellitus for previous 8-12 weeks and is not suitable in the case given in the question.

• Serum fructosamine is formed due to non-enzymatic glycosylation of serum proteins mainly albumin.
• It represents glycemic control for preceding 1-2 weeks.
• Normal values are 200-285mcmol/L

Advantages of serum fructosamine are:
1. Useful in Haemolytic states which affect Interpretation of glycosylated haemoglobin.
2. Evaluation of glycemic control at the time of conception in a woman with pre-existing diabetes mellitus.

• During exercise the muscles will consume sugar; hence sugar levels can be normal in a diabetic patient.
• However in malnourished patients, bedridden, infection state and severe emotional stress false positive OGTT is seen. It can be explained by catecholamine surge and release of counter- regulatory hormones.

• High Glycemic index foods have values of 70 or greater and include baked potato, white bread and white rice.
• Low Glycemic index foods have values of 55 or lesser and include multi grain breads, pasta, legumes.

• Sulfonylureas act on receptors in pancreatic beta cells resulting in closure of potassium cells. This results in depolarization of Beta cell and release of insulin.
• Glyburide has the highest affinity/ insulinotropic action while tolbutamide has least affinity.

• Glyburide should not be used in patients with liver disease and CKD due to risk of hypoglycaemia.
• Glipizide, Gliclazide and Glimepiride are metabolised by liver and hence can be used in patients with CKD.

• Thiazolidinediones are contraindicated in patients with Cardiac status NYHA grade III and IV due to propensity cause fluid retention.
• Increased fracture risk is mentioned in women in both pre and post-menopausal women.
• Troglitazone the first medication from this class of drugs was withdrawn due to fatal liver failure.
• Like biguanides, Thiazolidinediones do not cause hypoglycaemia.

All GLP-1 receptor agonists are associated with increased risk of pancreatitis. Exenatide is documented to cause haemorrhagic/ necrotising pancreatitis.

• A patient of type 1 Diabetes mellitus is on Continuous subcutaneous insulin infusion. Due to device malfunction/ tubing malfunction the delivery of insulin was halted.
• Since patients of type 1 diabetes are ketosis prone, she has gone into Diabetic ketoacidosis. The low bicarbonate points to acidosis.
• The patients elevated blood sugar is drawing water into the intravascular compartment and hence volume expansion explains the sodium deficit. However there is no need of hypertonic saline as correction of hyperglycemia by insulin shall suffice in managing sodium values.
• Hypertonic saline is only given in acute onset hyponatremia with neurological features.
• If severe hypophosphatemia can develop (<1 mg/dl), phosphate should be replaced at no more than 3-4m mol/h via infusion.
• Potassium replacement should be started in 2^nd to 3^rd hour as acidosis begins to resolve.

Long acting insulin have onset of action after 30minutes of administration and do not exhibit a peak action unlike other forms of insulin.
They are designed to provide constant values in blood for the entire day.
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Effect of anti-diabetics on weight

• Metformin and DPP-4 inhibitors are weight neutral
• GLP-1 Agonists, SGLT2 inhibitors and Pramllntide promote weight loss
• Sulfonylureas, insulin and Pioglitazone are associated with weight gain

• Repeated injections of insulin at the same site can lead to lipo-hypertrophy.
• Excess injection can lead to blood sugar < 50mg% and explains neuro-glucopenia.
• Excess bed time injection of long acting insulin will lead to 3 am hypoglycaemia. This leads to release of counter-regulatory hormones and results in pre-breakfast hyperglycemia.
• In case of exogenous insulin administration, the ratio of insulin/ C- peptide will be >  1.0.

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 patient is having 3am hypoglycaemia which is probably due to excess bed time insulin dose. This is triggering release of counter-regulatory hormones, resulting in pre-breakfast hyperglycemia. This is called as Somogyi phenomenon.
• It can be treated by giving lower dose of intermediate insulin at dinner time or more food at dinner time.
• Dawn phenomenon is due to reduced tissue sensitivity to insulin between 5am to Sam.

The UKPDS (United Kingdom Prospective Diabetes Study group) regarding prevention of microvascular and macrovas-cular complications demonstrated that BP control is more significant than glycemic control in patients with type 2 Diabetes mellitus.

• The most common complication in type 2 diabetes mellitus is neuropathy affecting 50% of patients.
• Distal symmetric polyneuropathy leading to loss of function in stocking glove pattern is the leading presentation of diabetic neuropathy.

The image shows Semmes Weinstein filament test, which is performed to evaluate for diabetic neuropathy. It is a low cost, easy to apply, rapid test.
This assessment tool consists of a set of monofilaments that vary in thickness and diameter, the gradient forces of these monofilaments ranges from .086 gm to 448gm. These monofilaments are used to map out sensory loss.
Light touch

• 10 g Semmes-Welnstein monofilament
• Podiatrist test 10 sites
  • Apex 1/3/5 toes
  • Plantar MTPJ's of 1/3/5
  • 2 x medial longitudinal arch
  • Plantar heel
  • Dorsum of foot

• Sensitive radioimmunoassay methods measure small amounts of urinary albumin in contrast to less sensitive dipstick strips. Hence choice A is wrong.
• 24 hour urine albumin values are affected by exercise, dietary protein and sustained erect posture. This problem is circumvented with spot sample urine albumin to urine creatinine values. Hence choice B is wrong.
• Most common cause of death in type 2 diabetes mellitus is myocardial infarction. Hence choice D is wrong.
• Microalbuminuria has been shown to correlate with elevated nocturnal blood pressure in diabetics. This can explain benefits of ACE inhibitors in reducing microalbuminuria.

Diabetic amyotrophy presents with severe pain in front of thigh. Subsequently weakness and wasting of quadriceps develops. Management involves analgesia and improved diabetes control. The symptoms improve over 6-18 months,

The preferred sites for insulin administration are:

1. Abdomen
2. Anterolateral aspect of thigh
3. Dorsal Arm

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The route of administration is subcutaneous and abdominal wall has substantial subcutaneous fat. The site of injection can be rotated to prevent local site scarring. The rate of absorption from abdominal wall is fastest.

• Random blood sugar will help in evaluation of Non-ketotic Hyperosmolar coma versus hypoglycaemia as the cause of unconsciousness.
• Diabetics have accelerated atherosclerosis and NCCT will help in ruling out possibility of stroke
• ECG will help in evaluation of current status of atrial fibrillation as it can lead to embolic stroke. Hence, if required, rhythm control will be initiated.
• Lumbar puncture is contraindicated in patients with bleeding diathesis/novel anticoagulants. The most common site of bleeding after lumbar puncture in patients on anticoagulants is epidural space. This leads to neurological complications with very poor response to surgery.
• Moreover even if we are suspecting SAH, NCCT is the first investigation.

• Metformin is excreted via the kidney and hence urine MICRAL (Microalbuminuria) test and KFT should be done to estimate GFR of the kidney.
• Failure to perform these tests can result in accumulation of metformin and development of metabolic acidosis.
• Both Sitagliptin and Canagliflozin (SGLT-2 inhibitor acting on PCT) are metabolised by the kidney.
• Linagliptin has non-linear pharmacokinetics and unlike other DPP-4 inhibitors, has a largely non-renal excretion route. It is excreted unchanged in the faeces and urine. The effective half-life is 12 hours.

• Polymorphism in promoter region of insulin gene, CTLA-4 contributes to susceptibility to type 1 Diabetes mellitus.
• The most common cause of type 1 diabetes mellitus is autoimmunity. Most patients have DR3 and/ or DR4 haplotype
• Haplotype DQA 1*0301 is strongly associated with type 1 DM.
• Concordance of type 1 DM in identical twins is 40-60%
• Chances of type 1 DM if single parent has type 1 DM is only 3-4%

The pancreatic beta cells secrete Islet amyloid polypeptide or amylin. It is found to be major component of amyloid fibrils found in islets of patients suffering from type 2 diabetes mellitus.

• In diabetic ketoacidosis, the elevated blood sugar due to osmotic diuresis leads to polyuria. The stimulation of osmoreceptors will lead to increased thirst.
• DKA can lead to early presentation of type 1 DM but more frequently occurs in patients with pre existing diabetes.
• In DKA serum ketones are present and detectable at dilutions of 1:8. Urine dipstick using sodium nitroprusside can help in detection but plasma beta hydroxybutyrate is preferred.
• Serum bicarbonate levels in DKA are < 10m mol/L.