Treatment of type two Diabetes (NIDDM) – By Dr. Gnana Sankaralingam
Type two diabetes is either due to lack of sufficient insulin or inability to utilise available insulin. It onsets in middle aged obese individuals, but elderly patients may be thin. In the diagnosis of diabetes, two values are used, viz base line level (fasting) and two hours after a meal (post-prandial). WHO criteria for diabetes is 7 mmol/l for fasting and 11 mmol/l for post prandial. Between 6 to 7 mmol/l or 10 to 11 mmol/l are considered as pre-diabetic. Three methods are available in the tretment : diet alone, diet and oral hypoglycaemic drugs, and diet and insulin. About 50% of new cases could be controlled adequately by diet alone, 20 to 30% will need oral hypoglycaemic drug and 20 to 30% will require insulin.
Person could be labelled diabetic depending on one of three blood tests. Raised random glucose level associated with symptoms like polyurea and weight loss, raised fasting blood glucose level or raised glycated haemoglobin (HbA1c). Once diagnosed options should be discussed with the patient. First line is life style management for those with HbA1c lower than 7% or 53 mmol/mol. Those with HbA1c 7 to 8.0 % or below 64 mmol/mol, should also be started on life style management before placing them on drugs. Life style improvement to be followed are exercise such as walking for two miles and diet control to reduce wieght. Do HbA1c in 3 months, and if it is elevated, consider giving oral hypoglycaemic.
Drug of choice for monotherapy is Metformin other than those with impairment of kidneys. Common side effect of it is digestive disturbance and rarely lactic acidosis. In the above patients, in addition to life style improvement, Metformin is given as single dose after dinner of 500mg. Monitor every four weeks and if control not achieved, increase dose step wise to 500mg twice daily, 500mg in the morning and 1000mg at night and 1000mg twice a day. If at any stage glucose is controlled, continue with the same dose. After increasing it to the maximum, if HbA1c is still up, consider adding another oral hypoglycaemic.
In the above patients or those who present for the first time with HbA1c of 8.0 to 9 % or between 65 to 75 mmol/mol, second drug is included. These are DPP-4 inhibitors, SGLT-2 inhibitors, sulphonylureas, glitazones or GLP-1 analogues. DPP-4 inhibitors suppress action of dipeptidyl peptidase 4 enzyme which destroys hormone incretin, which potentiate insulin thereby increasing the action of insulin. SGLT-2 inhibitors act by blocking the protein sodium glucose co-transporter 2 in kidney leading to removal of glucose, sodium and water. Sulphonylureas stimulate pancreas to produce insulin, which carries a risk of hypoglycaemia. Glitazones or Thiazolidinediones increase insulin sensitivity in peripheral tissues, but due to fat synthesis in liver, cause obesity. Glucagon Like Peptide (GLP-1) receptor agonists act like GLP-1 enzyme secreted in the intestine which lower glucose absorption. Start with low dose and increase gradually. If control is achieved with dual therapy, continue with it.
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If after three months HbA1c is still elevated or in those who present for the first time with HbA1c of 9 to 10 % or between 76 to 85 mmol/mol, another drug among above is added. Start with low dose and increase gradually. If control is achieved with triple therapy continue with it. If after three months HbA1c is still elevated or in those who present for the first time with HbA1c of above 10% or 86 mmol/mol or those in a catabolic state with HbA1c and FBS raised, Insulin becomes necessary. Before starting Insulin, find out the reason why it is not controlled and if that is due to noncompliance of diet or drugs, correct it.
Insulin maintains blood sugar level throughout the day and after a meal when sugar level peaks, insulin is secreted in response which brings the sugar level to base line in two hours. To achieve this in a diabetic, insulin is given to synchronise with the peaks. There are different types of insulins, short or rapid acting starts within 30 mins and lasting for 4 – 8 hours, intermediate acting peaks in 6 – 12 hours and lasting for 12 – 18 hours and long acting which has no peak but lasts for 24 hours. Due to risk of hypoglycaemia, metformin could be continued but others given with caution and HbA1c be maintained at 7% or 53 mmol/mol. Two ways of administering insulin are basal bolus regimen and mixed regimen.
In basal bolus regimen, begin with basal long acting insulin to control baseline level. Give it at bedtime starting with 10 units or 0.1 – 0.2 units / kg and check fasting level every three days, increasing the dose by 2 units. If at any stage control is achieved, continue with the dose. If fasting target is achieved, look at post prandial levels and HbA1c. If fasting target is reached but post prandial or HbA1c is high or if insulin required is higher than 0.5 units / kg, bolus short acting insulin is added. Start it before meal where post prandial level is maximum with 4 units or 10% of basal insulin. Check post prandial level every three days, increasing the dose by 2 units. If at any stage control is achieved, continue with the dose. If control is not achieved with single bolus, Insulin can be added step wise before other meals also. Another way is to calculate total dose at 0.3 to 0.5 units / kg, and give 50% as basal and other 50% as bolus divided equally among three meals and regulate it. When on bolus dose patient must eat immediately after receiving insulin to prevent hypoglycaemia.
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In mixed regimen, pre-mixed Insulin (short acting and long acting combined) is used, where long acting control base line and short acting control peaks after meals. There are numerous types available. Figure given in the mixed insulin phial denotes proportion of short acting. Calculate total dose at 0.3 to 0.4 unit / kg or sum of basal and bolus doses and give 2/3 in morning and 1/3 in evening and regulate it. It is not effective as basal bolus one. Though it controls morning and evening levels, there is overall hyperglycaemia. As they have to prick twice, patients prefer it as compared to seven pricks in other regimen. If after meal spikes are high while on insulin, glucosidases or amylin analogues may be used.
New discoveries in treatment include once a week injectable long acting insulin (Glargine) which control basal level, inhaled insulin (Afreeza spray) taken before meal which control peaks (post prandial level) and is faster and effective than injection, SGLT-2 inhibitor Sotagliflozin which increases sugar excretion in kidneys as well as reduces sugar absorption from gut, Mounjaro Tirzepatide which act like both GLP-1 and GIP enzymes, given as once a week injection and ‘Artificial Pancreas’ which is worn as patches on skin, which continuously check glucose level and deliver the needed insulin, with patients doing nothing.
