59 year old obese diabetic patient with a history of cardiovascular disease who is not controlled on metformin and gliclazide
Diabetes was recorded back in ancient time. The word itself is a greek word derive from diabaínein, which is coined by Aretaeus of Cappadocia. It is first recorded in English during 1425. Thomas Willis has added mellitus on top diabetes to explain the sweet taste of urine. Mellitus is derived from the latin word meaning honey. Matthew Dobson later has confirmed that the sweet taste of urine is due to excessive of sugar in the urine and blood of people with diabetes.(1)
Sir Frederick Grant Bant and Charles Herbert Best later have clarified the role of pancreas and reveal the existence of insulin in 1921. They even demonstrated that dogs that were induced with diabetes can be reverse by giving them an extract from pancreatic islets of Langerhans, which were then obtained from healthy dogs.
In 1922, an effective treatment for diabetes is found when Banting, Best and colleagues managed to purified the hormone insulin from bovine pancreases. They received the Novel Prize in Physiology of Medicine ten years later. Because of this, World Diabetes day has been held on Banting's birthday to honour his contribution which is on November 14th.
Diabetes mellitus is define by the level of hyperglycaemia that has cause several conditions. This results risk of microvascular complications like retinopathy. An increased risk of macrovascular complication can reduce life expectancy like ischaemic heart disease or peripheral vascular disease.(2)
It is divided into two types generally. Type 1 is due to the able to produce insulin as a result of the pancreatic beta-cells being destroyed. Patients who are type 1 diabetic are insulin dependent and ketoacidosis often seen in them. They rely on insulin treatment as oral antidiabetic drugs are rendered useless in this situation.(2) On other hand, oral antidiabetic drugs are useful for type 2 diabetes where it is due to receptor not being sensitive or not sufficient to insulin. Although it sounds like less severe when compared to type 1 diabetes but when it is look in long term, it is as severe as type 1 diabetes. Often, patient refers type 2 diabetes as 'mild diabetes' but this is just a misconception.(2)
There are other type of diabetes put these are secondary which is a result from other causes like endocrine disease. Gestational diabetes is one of it and only presented in pregnant women. They have 60% chance of developing into type 2 diabetes and the risk could be increase if they do not manage their weight well. Impaired glucose tolerance is impaired glucose homeostasis, and a risk f 2-5% to be developed into diabetes. It is usually associated with cardiovascular risk.
In 2000, according to the World Health Organization, at least 171 million people worldwide suffer from diabetes, or 2.8% of the population. Its incidence is increasing rapidly, and it is estimated that by 2030, this number will almost double. Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. UK has 1,765,000 diabetes cases in 2000 and WHO has projected that this will increase to 2,668,000 by 2030.(3) As for the world, 171,000,000 was found to be diabetic in 2000 and it is predicted that it will increase to 366,000,000 by 2030 which is about 2.5 times more if it is not well control.(3) In North America, 26 million people have diabetes in United State alone, and from those, 7 million remain undiagnosed. Global prevalence in 2000, where India (31.7million) rank as the top, China (20.8 million) rank as 2nd, U.S (17.7 million) as the 3rd, Indonesia (8.4 million) as the 4th, Japan (6.8 million) as the 5th.(4)
Diabetes is associated with serious long-term complications including microvascular and macrovascular disease, which impose an additional socio-economic burden and account for substantial healthcare costs [2] D. Yach, D. Stuckler and K.D. Brownell, Epidemiologic and economic consequences of the global epidemics of obesity and
diabetes,
Nat. Med. 12 (2006), pp. 62-66. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (173)and Improved glycemic control in people with diabetes reduces the risk of long-term complications.(5) Diabetes is not well controlled even though patients are on antihyperglycaemic thereapy over the time.(6) 80% of diabetes death occurred in low and middle income countries and 50% of them died to cardiovascular disease.(7)Although it has been found that diabetes is a risk factor to coronary heart disease and ischaemic stroke, (8)(9) there are uncertainties on its effect when categorize by age or gender. (10)(11) The extent to which diabetes is associated with fatal versus non-fatal myocardial infarction or ischaemic versus haemorrhagic stroke is also unknown.(12)(13) However, it is known that it is a 2 times to 4 times the risk when associated with coronary heart disease. (14)
A ten year post-randomisation follow up of uKPDS 33 and 34 suggested a long term beneficial effect of more intensive glycaemic control in the early years after diagnosis of diabetes although similar control in intensive and conventional groups after study close-out. Patient who were treated with insulin or sulphonyurea and metformin has been shown to reduce mortality.(15)
A study found that patient with 5.60mmol/L-6.99mmol/L of blood glucose has moderate risk but it very high when they have a concentration of 7mmol/L or more.(16)
WHO has define that to diagnose diabetes, fasting plasma venous glucose concentration must be more than 7.0mmol/L with classic sypmtoms present, like polyuria, polydipsia and unexplained weight loss.(15)
In united states, $132 billion was estimated to be the cost to treat diabetes as claimed the The National Diabetes Information Clearinghouse. In a study, it was found that total cost of treatment was S9643 higher for a diabetic patient when compared to control. Costs for the 8 years following diagnosis were higher in diabetic subjects with a total difference in average total costs of $18,057 between a type 2 diabetic patient and a matched control subject. As for western European countries, 2-7% of the national health care budgets are accounted for the cost of treating diabetes. It is estimated that this cost will be increase from £1.8 billion in 2000 to £2.2 billion by 2040, which is an increase of 24%!(17)
Treating diabetes can be divided into several forms. Metformin is usually started to help treat type 2 diabetic patient. Metformin decreases hepatic glucose production and increase the disposal of glucose which is done so by activating energy-regulating enzyme AMP-kinase in liver and muscle. At the same time, it also helps suppress appetite thus help in weight reduction.(15)
Effectiveness of metformin as a monotherapy was reviewed when it is compared with placebo. It has shown
HbA1c (standardised mean difference, SMD -0.97% (-10.60 mmol/mol), 95% CI -1.25 (-13.66) to -0.69 (-7.54)), and FPG (SMD -0.87, 95% CI -1.13 to -0.61) which is a benefit. When compared with diet, metformin showed more benefit for HbA1c (SMD -1.06% (-11.58 mmol/mol), 95% CI -1.89 (-20.66) to -0.22 (-2.40)) and total cholesterol but no difference for FPG, BMI, HDL cholesterol, LDL cholesterol, triglycerides, or blood pressure.(15)
Metformin has been reported to cause diarrhoea and hypoglycaemia but these two side effects are rare but nauseas are often seen especially with a high dose of 3g daily.(18)
Sulphonylureas increase endogenous release of insulin from pancreatic beta cells. First generations like acetohexamide and chlorpropamide are rarely use now in UK as it is preceded by the second generation like gliclazide, glipizide and glimepiride. It is reported that sulphonylureas has a tendencies to cause hypoglycaemia. A Scottish population based study showed that one person with type 2 diabetes in every 100 treated with a sulphonylurea each year experienced an episode of major hypoglycaemia, compared with one in every 2,000 treated with metformin and one in every 10 treated with insulin.(15) However, the usual indication that patient is experiencing hypoglacaemia as side effect could indicate that overdose of sulphonnylurea is given.(18)
Since patient is not well controlled on metformin and sulphonylureas (gliclazide), insulin should be given on top of the current regimen.
Regulation glucose level in the body has been done by the body itself so giving insulin will tremendously help lower or control glucose level. Insulin is only given via subcutaneous injection. A short acting insulin should be given first before meal and a long acting insulin to be given at bedtime. This regimen will need multiple injection and lipodystrophy may occur.(18) This regimen has best glycaemic control when compared to the pre-mix insulin.
Glucagon like peptide-1 agonists like exenatide or liraglutide can be introduce to replace insulin if patient has religion view against using insulin. GLP1(glucagon like peptide-1 agonists) bind and activate the GLP1 receptors inducing insulin secretion. This is only helpful when type 2 diabetic patient has yet to progress into type 1. However, GLP1 is only available in the subcutaneous route as its oral route is not readily bioavailable. Doses for exenatide can be started 5mcg twice daily within 1 hour before 2 main meals, which is 6 hours apart.(18) There is a possible spike of glucose level if patient is to continue on their 3 main meals a day. However, it is found that GLP1 is able to slow gastric emptying, which slows the absorption of glucose following meals thus, reducing appetite. Therefore, the worry of 3 main meals could spike the glucose level may not be a concern.(15) However, it is found that exenatide produce side effects like nausea and vomiting which may deterred patients to use if they are not able tolerate it well.(19) If patient dislike to inject twice daily, liraglutide can be prescribed to replace exenatide as it is a once daily dosing. It has the same mechanism as exenatide which is a GLP1 agonist.(20)
If patient is unwilling to self-inject, and prefer to have oral medication, Thiazolinediones can be given on top of metformin and gliclazide. Thiazolinediones like pioglitazone and rosiglitazone helps increase insulin sensitivity by activating nuclear receptor. Doing so will promote esterification and storage of free fatty acids that are circulating in subcutaneous adipose tissue. Studies has shown that Pioglitazone is effective at lowering HbA1c on its own or in combination. It is shown that it is able to reduce by 0.64%-1.26% when combination therapy is given with a dose at 15-30mg daily. The combination therapy can be given with metformin, sulphonylureas or insulin. However, it is not suitable for patient with cardiovascular disease as it will increase the risk of mortality.(15)(18)
Beside pharmacological approach on treating diabetes, patients who are smokers should be targeted for smoking cessation. A study in Sweden found that diabetic smokers are not able to comply with their antidiabetic medication resulting glucose level not well controlled. In this study, it has been shown that smoking is associated with insulin resistance as well as microalbuminuria.(21) Other than that, smoking is a risk factor cardiovascular disease as well. It has been shown that men who smoke are 3 times likely to die at the age of 45-64 years.(15) Nicotine patch program should be introduced to these patients.
Patients should be doing exercise as well to help with their disease. It is able to reduce the risk of type 2 diabetes and preventing of having it. However, the studies indicated that this protective effective when patient has consistently done exercise for a minimum of 4 years.(15) Another studies found that it is not aerobic exercise that helps in lowering remant like lipoprotein but it is resistance exercise. This study was conducted using randomised trial and seems to be a high quality evidence.(22) With this, patient should do exercise in order to help with their condition.
Although diabetes is associated with obesity, there is no concrete evidence yet indicating a good control of diet able to help with type 2 diabetes. This is mainly because most of the studies done have high dropout resulting data to be not reliable. However, SIGN recommended an optional choice for patient whether they want to take up diet control. There are evidence that patient with diabetes and cardiovascular disease should not be consuming omega-3. Study has shown that patient taking this have an increase in low density lipoprotein cholesterol even though triglycerides are reduced. They should not be taking vitamin E (tocopherol) as well with a dose of 500mg as it has been shown that it will increase heart rate and blood pressure.(15) If they do take omega-3 and vitamin E, this will unnecessary increase their risk of mortality instead of doing them any good.
There is no evidence showing that diabetic patient should not consume alcohol, but rather, it does shows that people do not have an increase risk or hospital admission with acute coronary syndrome, when they consume less alcohol. Thus, alcohol consumption should be done in moderation or preferably, none.(15)
So, all in all, patient should be started on insulin if he is willing otherwise alternatives like exenatide can be given in place of insulin on top of its current medication.
