Case Studies

Presenting Complaints

• General ill health & getting tired easily
  -since last two years
• Excessive urination
  -since last 6 months
• Waking up at night to urinate
  -since last 3 months
• Loss in weight
  -2.5 kg over the last 2 months

Sundarajan is an agent for an insurance company and has to travel about 30-40 km every day in the course of his 'outside-office' work. He was apparently asymptomatic till about 2 years ago when he started feeling tired more easily than before. He thought it is because of the strenuous demands of his work. He consulted his doctor who enquired into everything, elicited the presence of a history of smoking and chronic cough that had lasted more than 3 months. An X-ray of the chest was prescribed, it did not reveal any abnormality. Sundarajan was told to stop smoking, prescribed a haematinic and told to eat a more nutritious diet with more milk and egg every day.

His feeling of tiredness reduced slightly, but persisted to some extent in spite of drastically cutting down his smoking, increasing his diet quantity and improving his quality. About 6 months ago he noticed that he was urinating more frequently even in summer, but he ascribed it to his excessive thirst and water drinking. About 3 months ago he noticed that he had to get up almost every night to pass urine. Around the same time he noticed that his pants were becoming loose, and he appeared to be losing weight.

On the advice of his friends and colleagues in the office, he consulted his doctor again and was referred to a physician. After a detailed history and examination, his consultant physician ordered some investigations. The reports were as follows:

Sundarajan's doctor saw the reports. The diagnosis was obvious and the doctor had to explain it gently to Sundarajan. Fortunately, while taking the history, the doctor has enquired about family history of diabetes and knew that both of Sundarajan's parents had diabetes. Both had received oral medication for diabetes and both had a died of heart attack at relatively young age [in their late fifties]. Neither of Sundarajan's two elder siblings were known to have diabetes. The doctor therefore told Sundarajan that the report confirmed his suspicion viz. that he was dealing with a case of diabetes.

Managing Diabetes

Diabetes mellitus is a chronic metabolic disorder caused by deficiency of insulin secretion and characterized by hyperglycemia and tendency to develop acute and chronic complications. Two type of diabetes mellitus are well described.

Type 1 diabetes is caused by immune mediated damage to the pancreas and characteristically occurs at a younger age, patients are prone to develop ketosis on account of severely diminished or absent insulin secretion, and require exogenous insulin administration in order to prevent ketosis. Markers of immune mediated destruction of b-cells include glutamic acid decarboxylase [GAD] antibodies and inlet cell antibodies [ICA], (among other) and are present in 80% of these patients at presentation. However, these investigations are not done in routine clinical practice.

Type 2 diabetes generally occurs at an older age, and there is no evidence of immune mediated damage to the b-cells of the pancreas, but insensitivity to insulin action and insulin secretory defect/s are present. It is often associated with obesity, and the hyperinsulinemia which is often demonstrable in these patients is ascribed to a compensatory mechanism by the pancreas to overcome insulin insensitivity. However, hyperglycemia supervenes after a variable period, when the degree of insulin insensitivity cannot be compensated for even by the maximal insulin secretion by the b-cells.

In contrast to the general impression that adult onset diabetes is associated with obesity; some patients with diabetes are 'lean' i.e. with a body mass index [BMI] less than 19. In India, and in other developing countries, it is believed that 'lean' type 2 diabetes is a distinct entity because though these patients are not prone to develop ketosis, they do not respond well to oral hypoglycemic agents, and require insulin administration for control of hypoglycemia. These patients also have higher rates of ICA and GAD antibody positivity, and become insulin dependent in due course of time, and this type of diabetes has been called latent autoimmune diabetes of adults [LADA].

Diabetes mellitus occurring in the adult is often characterised by non-specified symptoms which lead to a delay in diagnosis of the condition. The basic defect in diabetes mellitus is glucose overproduction by the liver, and inability of peripheral tissue to utilise glucose effectively. Plasma glucose levels thus rise slowly over a period of time and postparandial glycemic excursion are higher and more prolonged than those seen in non-diabetes persons.

One of the earlier non-specific symptoms to appear in diabetes is a feeling of tiredness and easy fatiguability, because skeletal muscle cannot take up glucose effectively. As plasma glucose levels rise, and the renal glucose reabsorption threshold is exceeded, glycosuria - the occurrence of glucose in urine - results, leading to the symptom of increased thirst, increased water drinking and passage of excessive quantities of urine. This may be insidious on account of the slowly developing nature of the defect and many patients do not even realise it for prolonged periods. Loss of glucose in urine and breakdown of muscle protein for energy lead to weight loss in the person with diabetes.

Therapy

Sundarajan was not surprised to hear this. Some of his friends had in fact told him to get his, blood glucose' tested earlier. The doctor then told Sundarajan about diabetes - how the pancreas produces insulin and what insulin does, and what is wrong in diabetes. He talked about the methods of treating diabetes, the importance of proper diet, regular physical exercise, drug therapy in diabetes, and the need for regular monitoring of blood glucose levels.

As Sundarajan's current blood glucose levels were high, and he had lost weight; his doctor decided to start him on insulin treatment, and observe the results. Sundarajan was prescribed:

• Human Mixtard 12 I.U. every morning before breakfast and 8 I.U before dinner

• 3 days later his fasting and PP plasma glucose values were 180 and 220 mg/dl respectively.
• 7 days later they were 140 and 160 mg
• No episodes of hypoglycemia were reported by Sundarajan in the first week of Human Mixtard® therapy.
• His symptoms of nocturia, polyuria and easy fatiguability had been relieved and he had started feeling his 'normal' self again.

Although the usual dose for initiating insulin therapy in type 2 diabetes is generally 0.2 I.U/kg body wt/day; in this case the doctor decided to start with a higher dose of 4.0 I.U/kg body wt/day i.e. 20 units per day divided into two unequal portions of 2/3 (12 units) in the morning (pre breakfast) and 1/3 (8 units) in the evening (pre dinner). The doctor knew that once the hyperglycemia was reasonably well controlled he would be able to reduce the dose of insulin.

Human Mixtard® is a biphasic premixed insulin formulation containing 30 % as rapid-acting soluble insulin and 70 % as intermediate-acting NPH insulin. It is preferred for initiation as well as continuation of treatment, if required, because of the following reasons:

• It provides adequate and timely insulin for basal as well as meal stimulated requirements for most patients [more than two thirds]
• It minimises the dosing errors by patients or nursing staff because, being a premixed insulin, it eliminates the necessity of mixing two different insulin formulations
• It thus becomes more convenient for patients (or their relatives) to self-administer (or administer to the patient) at home, if required.

Follow Up

Sundarajan was asked for a follow up check after every month. He was prescribed Lifescan glucometer to checkup his blood glucose regularly at home. He is now asymptomatic and feels more energetic than before.