Diabetes Mellitus

Notes
  • Diabetes mellitus is a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.

Types of Diabetes

  • Type 1 diabetes: also known as Insulin Dependent Diabetes Mellitus (IDDM), affects mainly young people below 30yrs; associated with ketoacidosis (DKA) and pancreatic auto antibodies may be detected.
  • Type 2 diabetes: Non Insulin Dependent Diabetes Mellitus (NIDDM), affects mainly people above 30yrs who are obese and mostly accompanied by hypertension.
    • Gestational diabetes: It arises from the fact that pregnancy causes substantial insulin resistance in all women and a small number of them develop gestational DM.
Symptoms
  • Hyperglycemia
  • Glycosuria
  • Polyuria
  • Polydipsia
  • Polyphagia
  • Dehydration
  • Orthostatic hypotension
  • Change of mental status and weakness due to dehydration
  • Predisposition to bacterial and fungal infections
  • Nausea
  • Vomiting
  • Weight loss (in Type 1) due to hyperglycemia.
Diagnosis
  • Fasting Plasma Glucose (FPG) levels: should not be more than 7.8mmol/L.
  • Random blood glucose: more than 11.1mmol/L in a symptomatic patient.
  • Oral Glucose Tolerance Test (OGTT): more than 11.1mmol/L.
  • Urinalysis for protein, sugar and ketones.
  • HbA1C (glycosylated Hb): Equal or more than 6.5% in DM or 5.7-6.4% in prediabetes or at risk of DM.
  • Screening for complications: Foot examination; serum creatinine; serum lipid profile; funduscopic exam;  urine testing proteinuria and microalbuminuria
Differential
  • Cystic fibrosis
  • Drug-induced glucose intolerance
  • Gestational diabetes Glucose intolerance
  • Pancreatitis
Management
  • Treatment goals: FPG levels of 4.4-6.7mmol/L during the day (5.6-7.8mmol/L at bedtime); HbA1C levels of less than 7%; prevention and management of the complications.
  • Treatment is based on the following: diet and exercise; insulin for IDDM; oral antihyperglycemics and/or insulin for NIDDM and ACE inhibitors, statins and aspirin to prevent complications.
  • Diet control: Consult a dietician; strict adherence to meal schedule; to target a caloric intake of 35Kcal/kg/bw for IDDM and 15-20Kcal/kg/bw NIDDM; food composition of 50-60% carbohydrates in complex form (such as rice, peas and beans), 10-20% proteins (such as beans, soya beans and lentils), 20-30% fibres (such as bran); artificial sweeteners like saccharin and aspartate increase palatability of beverage. 
  1. Antidiabetics in the Essential Drug List (KE):
  • Glibenclamide 5mg tablets
  • Metformin 500mg tablets
  • Soluble human insulin injection 100IU/mL in 10mL vial and
  • Isophane biphasic human insulin (intermediate insulin 30/70) 100IU/mL in 10mL.
  • Potassium chloride injection 11.2 % 20mL
  • Glucose 5% , 500mL
  • Glucose 10%, 50mL
  • Glucose 50% 50ml
  • Sodium bicarbonate injection 1.4%
  • Sodium bicarbonate injection 8.4%
  • Normal Saline 0.9% , 500mL

 

  • Glibenclamide: Dose - initially 2.5mg daily before first meal. Increased by 2.5mg until blood sugar is under control [max 15mg daily, max. Single dose 10mg]
  • Metformin: Dose: 500mg TID or 850mg BD [Max.:3g. daily in divided doses w;ith or after meals].
  • Insulin:

In NIDDM insulin is indicated in the following situations: patient undergoing surgery; ketonuria; failure of oral antiglycemics; presence of infections and in renal failure; pregnancy.

Patient’s preparation for self-administration of insulin: psychological counselling for the long term treatment; signs and treatment of hypoglycemia; measurement of insulin to be injected; care of the neEDLes and syringes and technique of injection.

Dose of insulin: The starting dose should be 10-16 units of soluble insulin SC 30 minutes before meal TID. The dose is adjusted gradually in 5 unit aliquots to achieve plasma glucose range of 8.3-13.4 mmol/L in hospital and target the range of 4-10mmol/L at home. Once the blood glucose stabilizes at 8-11.0 mmol/L the patient is switched to the intermediate insulin whose dose is 2/3 of the total dose of soluble insulin. Normally 2/3 of the intermediate insulin is administered in the morning and 1/3 before supper.

Management of Diabetes Ketoacidosis (DKA):

  • Initial fluid replacement with normal saline then 5% dextrose until blood glucose is 12-14.5mmol/L then revert to normal saline until ketonuria is not detectable and fluid loss is rectified.
  • Ten (10) units IV then 10 units IM immediately followed by 6-10 units every hour until the blood sugar of 14mmol/L is reached. This is followed by soluble insulin 8-16 units SC 4-6 hourly then TID and subsequently intermediate insulin as previously described.
  • Correction of hypokalemia: the dose depends on the potassium plasma levels and it is administered slowly at a rate of 10-20mEq/hr (where 10mL of 15% KCL = 20mEq K); plasma K+ less than 3mmol to administer 40mmol/L of IV fluid, plasma K+ of 3-4 mmol to administer 30mmol/L of IV fluid, plasma K+ of 4-5 mmol to administer  20mmol/L of IV fluid, plasma K+ of 5-6 mmol to administer  10mmol/L of IV fluid.
  • Correction of acidosis (when pH is below 7.2 and potassium levels above 4mmol/L): NaHCo3 is used if decompensated acidosis starts to threaten the patient's life. Dose: 100-150 mL of 1.4% is administered initially then repeated every 30 minutes. Early correction of acidosis with NaHCo3 may worsen hypokalemia and cause paradoxical cellular acidosis.
  • Prevention of DVT: Heparin 2,500 units SC BD.
  • During the treatment of DKA the following parameters are monitored: potassium plasma levels (2hrly); plasma glucose levels (1hrly) and urine output (catheterize if no urine after 3hrs). Insert nasogastric suction if in comatose.

Management of diabetic hypoglycemia

any patient who is in coma or has altered level of conscious should be assumed to be hypoglycemia, blood sample taken to test for glucose followed by administration 20mL of 50% dextrose. For conscious patients give sugar-containing food such as sweets, soda and biscuits and monitor blood glucose every 15 minutes.

  • Patient counsellng and education: how to avoiding foot injury and foot care; need to eat regularly; need to seek medical advice in case of any injury; need to carry glucose or sweets in case of hypoglycemia; need to carry “Diabete Alert” card and need to join the diabetic support group.
  • Patient with diabetic foot: All patients with diabetic foot should be admitted.
  1. Therapeutics using drugs that are NOT in the Essential Drug List

Oral anti-hypoglycemics

  • Sulfonylureas

Chlorpropamide: Dose - 250mg OD initially [max. 500mg daily] taken after breakfast (NB: due to its long duration of action and side effects its use is not recommended)

Glimepiride: Dose - Initially 1mg daily before first meal. Increased by 1mg steps at 1-2 week intervals.  Usual max. 4mg daily. Exceptional max. 6mg.

Glimepiride / Metformin: Dosage - Dose depends on blood sugar level. Max dose 8mg/2000mg glimepiride and metformin respectively.

Gliclazide: For non-controlled release formulation of gliclazide: Initially 40-320mg daily in 1-2 doses. Max single dose 160mg. Max. daily dose 320mg. For controlled release formulation: Initially 60mg OD at breakfast; increase dose according to response, by 30mg OD at not less than 2-week intervals [max. daily dose 120mg]. Start at 30mg for the elderly and in renal impairment. For DiamicronÒ MR 60mg, one modified release tablet is equivalent to two DiamicronÒ MR 30mg tablets. The breakability of the DiamicronÒ MR 60mg ensures flexibility of dosing achieved.

Glipizide: Dose - Initially 2.5-5mg daily as single dose 15 to 30 minutes.

Gliquidone: Dose - Initially 15mg daily. [max single dose 60mg, max. daily dose 180mg]

Thiazolidinediones

A thiazolidinediones are effective only in presence of insulin. they bind selectively at peroxisome proliferator, an activated receptor-gamma found in the adipose tissue; skeletal muscle, and liver. Activation of these receptors modulates transcription of several insulin responsive genes that control glucose and lipid metabolism

Pioglitazone: Dose: Orally, initially 15 or 30mg OD without regard to meals [Max. 45mg].

Pioglitazone / Metformin / Glimepiride: The dose depends on the dosage of each component on stabilization.

Rosiglitazone: Dose: As monotherapy:  Initially 4mg/day orally administered OD or BD without regard to meals. If the response is inadequate after 12 wks, the dose may be increased to 8mg/day administered OD or BD. Combination with metformin: Initially 4mg/day orally administered OD or BD. If the response is inadequate after 12 weeks, the dose may be increased to 8 mg/day OD or BD.

Rosiglitazone / Metformin: The dose depends on the dosage of each component on stabilization.

  • Oligosaccharide:

Acarbose: Dose - Initially 25mg TID at the start of each main meal. Dosage may be adjusted at 4-8 weeks intervals, first to 50mg TID then, if required, to 100mg TID.

A carbamolylmethyl benzoic acid derivatives

Repaglinide: Dose - For patients previously untreated with a hypoglycaemic agent[s] and whose HbA1c is less than or equal to 8%: Initially 0.5mg orally [max. 16mg daily]. For patients previously treated with a hypoglycaemic agent and whose HbA1c is greater than or equal to 8%: initially 1-2 mg [max. 16mg daily]. It is taken 15-30 min before meal.

Dipeptidyl peptidase-4 [DPP-4] inhibitors:

Saxagliptin: Dose -5mg OD

Saxagliptin + Metformin XR: Dose - Normally 1 OD or the dose adjusted with individual drug.

Vildagliptin: Dose -50mg BD. When used in with a sulphonylurea, the dose is 50mg OD in the morning.

Vildagliptin / Metformin: Dose - 1 OD

 

  1. Other considerations
    • Pharmacokinetic profiles of various types of insulin therapies

 

Type of

Insulin

 

Onset of

Action

Maximum                     effect

Duration of action

Soluble

 

½ hr

2-3 hr, sooner if I.V

6-8hrs

Semi-lente

 

1 hr

6-10 hrs

12-16 hrs

Isophane

 

< 2 hrs

< 10 hrs

18-28 hrs

Lente

 

2-4 hrs

8-12 hrs

28-32 hrs

Detemir 

 

3-4 hrs

6-8 hrs

6-23 hrs

Glargine

 

1.5 hrs

None

24 hrs

NPH 

 

1-2hrs

4-10hrs

≥14 hrs

Aspart 

 

15mins

1-3hrs

3-5 hrs

Lispro

 

15hrs

30-90 mins

3-5 hrs

Glulisine

 

15-30 mins

30-60 mins

4 hrs

NPH/lispro or aspart or regular

 

15-30 mins

Dual

14-24hrs

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