Clinical presentation of diabetes

The clinical presentation of diabetes is heterogeneous, ranging from asymptomatic type 2 diabetes to the dramatic life-threatening conditions of diabetic ketoacidosis (DKA) and hyperosmolar non-ketotic coma (HONK). Patients with type 2 diabetes are often detected by opportunistic screening such as urinalysis or routine blood glucose tests in general practice, at health insurance checks or during attendance at hospital for an unrelated problem. This heterogeneity in presentation reflects not only the relevant diagnostic category into which the patient falls (type 1 or type 2), but also the point in the natural history of the disorder at which the diagnosis is made. Patients may present with macrovascular complications or the specific microvascular complications of diabetes.

Classical osmotic symptoms are may be present in type 2 diabetes – with the notable exception of significant weight loss, which is less common. However, a high index of clinical suspicion must be maintained so that asymptomatic cases are not missed. The absence of weight loss reflects the presence of sufficient secretion of endogenous insulin to prevent catabolism of protein and fat. Most patients with type 2 diabetes are overweight or obese, adding to their insulin resistance and hyperinsulinaemia. However lean type 2 diabetes is a definite entity particularly in developing countries.

Patients with diabetes tend to present in four main ways:

History and initial physical examination

Having obtained a detailed history, a physical examination should be undertaken (Table 2.3). The consultation should take place in appropriate and comfortable circumstances.

Table 2.3 Components of the comprehensive diabetes evaluation

BMI, body mass index; CHD, coronary heart disease; DKA, diabetic ketoacidosis; DSME, diabetes self-management education; GFR, glomerular filtration rate; HDL, high density lipoprotein; LDL, low density lipoprotein; MNT, medical nutrition therapy; PAD, peripheral arterial disease.

Source: American Diabetes Association (2011). Reproduced with permission.

Physical examination of the patient with newly presenting type 1 diabetes is usually unremarkable, although there may be evidence of recent weight loss and occasionally signs compatible with dehydration. Features of orogenital candidiasis or cutaneous sepsis are not uncommon, but are non-specific. The presence of vitiligo is consistent with the presence of autoimmune disease.

Screening for diabetes

There has been a significant increase in our understanding of the pathogenesis of type 1 diabetes. Approximately 10% of patients have a first-degree relative with type 1 diabetes and therefore subjects at high risk could be identified using a combination of immune, genetic and metabolic markers. However, even in high risk groups, screening is imperfect and the complex methodology is not available other than for clinical trials.

In the UK Prospective Diabetes Study (UKPDS), the severity of diabetes-related tissue damage correlated with the glycated haemoglobin (HbA1c) concentration at diagnosis of type 2 diabetes. Thus, there is the prospect that earlier intervention in patients identified by screening of asymptomatic at-risk individuals may prevent or retard chronic diabetic complications. Type 2 diabetes satisfies some of the major criteria for a disorder for which screening would be appropriate. However, there is little evidence to suggest that population screening is cost effective. It is appropriate to screen ’at risk’ groups (see Section 1).

Who makes the diagnosis?

Blood glucose and urine testing are valuable pointer to diabetes. Although glucose oxidase test strips are specific for glucose, glycosuria does not invariably indicate the presence of diabetes; the converse is also true.

In the UK, the diagnosis of diabetes is most commonly made in the GP’s surgery. Routine checks, insurance medicals and consultations with opticians or urologists also highlight cases of type 2 diabetes. Diagnosis on the coronary care unit following an acute myocardial infarction is not uncommon. Less commonly, the diagnosis is made when the patient presents with an established complication such as an infected neuropathic foot lesion or symptomatic diabetic retinopathy.

Most often, the diagnosis of diabetes relies on osmotic symptoms plus an increased laboratory blood glucose level, which can be fasting (≥ 7 mmol/L) or random (≥ 11.1 mmol/L).

Initial management

Having confirmed the diagnosis of diabetes, the crucial clinical question is whether insulin treatment is required. In the young patient with acute osmotic symptoms, weight loss and ketonuria, the decision to start insulin is straightforward. Similarly, the overweight or obese middle-aged or elderly patient with minor symptoms will usually be a candidate for a trial of dietary manipulation followed by metformin. In reality very few patients (< 20%) manage with diet alone for the usually advised period of 3 months.

Other oral agents including sulphonylureas, pioglitazone, gliptins etc. can be used from diagnosis, in addition to appropriate dietary measures.

Most importantly, the patient should be treated according to clinical need. However, an attempt should be made to place the patient with diabetes within the classification system. Often this assignment to a particular category is not possible with certainty and becomes clear only later. Initial therapy, therefore, does not necessarily confirm the aetiology. The difficulty at diagnosis centres on the degree of endogenous insulin deficiency, the rate of β-cell deterioration, the degree of insulin resistance and the presence of any intercurrent illness. Thus, patients with what proves ultimately to be type 1 diabetes will sometimes be treated with a trial of oral antidiabetic drugs, usually because the clinical and biochemical features were not classical; conversely, patients with type 2 diabetes may need insulin temporarily at diagnosis, especially if there is significant intercurrent illness.

It can sometimes be difficult to decide whether a newly presenting, middle-aged, non-obese patient with moderately severe hyperglycaemia has type 2 diabetes that will respond adequately to oral antidiabetic agents or whether the patient would be better treated with insulin from the outset. In this context, it should be remembered that, although relatively uncommon in the elderly, type 1 diabetes might present at any age.

The situation is complicated by increasing awareness of subtypes of diabetes in which insulin deficiency appears to be the predominant feature but which present less dramatically than classical type 1 diabetes. Moreover, even the presence of morbid obesity does not guarantee a diagnosis of type 2 diabetes; occasionally, obese patients present with marked osmotic symptoms and/or ketonuria indicative of insulin dependence.

Identification of patients with apparently autoimmune diabetes with a relatively slow onset can be problematic; the prevalence of latent autoimmune diabetes in adults (LADA) is not known but is perhaps under diagnosed (see Section 1). The diagnosis is often made retrospectively (glutamic acid dehydrogenase (GAD) + ve, anti-islet cell + ve) following the rapid failure of treatment with oral antidiabetic agents (see Section 3, p. 97). Useful clinical pointers at diagnosis suggesting that insulin may be required include:

Dietary manipulation ± oral agents may sometimes initially produce dramatic improvements. The issue of insulin dependence is particularly difficult in African Caribbean patients who may present with ketosis, even DKA, yet who ultimately prove to have diabetes that is controllable with oral agents or even diet alone.

Personal telephone contact is best to ensure that insulin treatment is initiated with the minimum of delay.

Influence of comorbidity

The presence of significant physical or psychological disease may be important modifiers of the presentation and management of diabetes. For example, if malignancy severely limits life expectancy in a patient with diabetes (perhaps precipitated by high-dose dexamethasone), the primary goals of management will be:

Insulin may be the most appropriate therapy; considerations such as the likely lack of efficacy of oral agents, concomitant renal and/or hepatic impairment may also preclude alternatives. As a general point, patients with diabetes are more likely to encounter significant comorbidity and may be predisposed to the development of important complications that influence treatment.

Lifestyle management

Lifestyle advice should be considered as part of the multidisciplinary intervention programme for all diabetic patients. Appropriate management of cardiovascular risk factors such as smoking, physical inactivity and poor diet is important for the prevention of macrovascular disease. Microvascular complications may also be affected by adverse lifestyle factors (e.g. smoking). However, helping patients to modify certain behaviours should take account of other factors such as the patient’s:

Patients should be offered lifestyle interventions that have a proven benefit in terms of both metabolic and psychosocial outcomes. These could include frequent contact with health professionals (including telephone contact). Psychosocial interventions should be varied and include behaviour modifications, motivational interviewing and patient empowerment.

Education interventions for diabetes are complex, varied, should be evidence-based and suit the needs of the individual. Health-care professionals should receive training in patient-centred interventions. The programme should have specific aims and learning objectives, and should support the development of self-management attitudes, beliefs, knowledge and skills for the patient, their family and carers. It should be structured, be resource effective and have supporting materials including pamphlets and other literature.

Trained educators should deliver lifestyle advice, and the programme should be appropriate to the age and the needs of the patients. The programme should also be assessed against key criteria and quality-assured to ensure sustained consistency.

Lack of head-to-head comparative trials makes it impossible to recommend any specific programme(s). Measurement of HbA1c is the most commonly used method for assessing outcome. However, HbA1c is a marker for glycaemic control and not for quality of life.

Healthy eating is of fundamental importance as part of diabetes health-care behaviour and has beneficial effects on weight, metabolic control and general well-being. Salt restriction is recommended for the prevention of hypertension and cardiovascular disease. Because of their high energy content, fats represent a major source of excess calorie consumption, particularly in convenience and junk foods. It is recommended that saturated fats, derived mainly from meat and dairy products, should comprise less than 10% of total energy intake. Use poly- or mono-unsaturated fatty acids (e.g. olive oil, rapeseed oil) in preference, but not in excess. In addition, consumption of trans-unsaturated fatty acids in excessive amounts may increase the risk of cardiovascular disease via alterations in lipoproteins.

Nutrition therapy

Individualized and detailed dietary advice requires the input of trained dietitians. However, the general principles that underpin the diet for most diabetic patient differs little in terms of macronutrient composition from the advice that is currently promulgated as a healthy diet for the population in general. Much more relevant to success in an individual patient is a realistic approach bolstered by adequate practical training for the patient (and relatives) and an ability to communicate the objectives effectively and sympathetically. At the outset, simple, easy-to-follow guidelines are appropriate (see Table 2.3).

Advised changes in diet are notoriously difficult for the patient to implement. This is especially so for the middle-aged or elderly patient with type 2 diabetes, 75% of whom are overweight or obese. Dietary modifications often run contrary to a lifetime’s habits and preferences, which have usually been reinforced by powerful social and cultural influences.

Obese individuals often significantly underestimate their daily calorie consumption. The oft-heard protests from patients about their supposedly miniscule daily food intake has to be gently but firmly repudiated if progress is to be made; recognition of the problem by the patient is usually a step forward. The difficulty lies in not alienating the patient in the process; a judgemental approach is unlikely to be successful. Increased levels of habitual physical exercise should also be encouraged.

The amount of carbohydrate ingested is usually the primary determinant of postprandial response, but the type of carbohydrate also affects this response. Intrinsic variables that influence the effect of carbohydrate-containing foods on blood glucose response include the specific type of food ingested, type of starch (amylase versus amylopectin), style of preparation (cooking method and time, amount of heat or moisture used), ripeness and degree of processing.

The glycaemic index of foods was developed to compare the postprandial responses to constant amounts of different carbohydrate-containing foods. The glycaemic index of a food is the increase above fasting in the blood glucose area over a 2-h period after ingestion of a constant amount of that food (usually a 5-g carbohydrate portion) divided by the response to a reference food (usually glucose or white bread). Multiplying the glycaemic index of the constituent foods by the amounts of carbohydrate in each food and then totalling the values for all foods calculates the glycaemic loads of food, meals and diets. Foods with a low glycaemic index include oats, barley, bulgur, beans, lentils, legumes, pasta, pumpernickel (coarse rye) bread, apples, oranges, milk, yoghurt and ice cream. Fibre, fructose, lactose and fat are dietary constituents that tend to lower the glycaemic response.

Carbohydrate in diabetes management

Recommendations:

Food and nutritional interventions that reduce postprandial blood glucose excursions are important in this regard, as dietary carbohydrate is the major determinant of postprandial glucose levels. Low-carbohydrate diets might seem to be a logical approach to lowering postprandial glucose. However, foods that contain carbohydrate are important sources of energy, fibre, vitamins and minerals, and are important in dietary palatability.

A number of practices are controversial:

Dietary recommendations for people with diabetes

Weight loss in overweight and obese individuals improves insulin sensitivity and glucose tolerance. Aim for weight maintenance and modest weight loss (5–10 kg in 1 year), which can improve health outcomes.

Weight loss via dietary intervention and therefore hypocaloric intake requires modifications to the type, quantity and/or frequency of food and drink consumed. A weight loss of approximately 0.5 kg per week results from a loss of adipose tissue that entails an energy deficit of 3500 kcal per week. This requires a daily energy deficit of a least 500 kcal per day. To ensure this deficit it is standard practice to aim for a 600-kcal deficit.

Most patients are able to lose weight actively for about 3–6 months, and so studies reporting weight losses at 12 months reflect a mixture of both weight loss and weight maintenance.

Calorie restriction

Daily energy requirements may be calculated from the patient’s height, age and physical activity using published tables. Adipose tissue contains about 7000 kcal/kg. Sustained weight loss in the obese will occur at a rate of around 0.5 kg/week with a reduction in daily calorie intake of 500 kcal (1.2 MJ). This represents a reduction of around 20% for most patients.

More rapid rates of weight loss will include structural protein (i.e. muscle) as well as fat; this is undesirable because resting energy expenditure, which is determined largely by fat-free mass, will decline as an adaptive response. Resting energy expenditure, which normally accounts for the majority of daily calorie consumption, represents the energy requirements for essential metabolic processes maintaining cell membrane potentials and body temperature. The observation that, on average, the obese have higher resting energy expenditures than the non-obese means that maintenance of body weight requires a proportionately greater calorie intake. Physical exercise, in conjunction with calorie restriction, will help preserve fat-free tissues, thereby maintaining resting energy expenditure; this combination offers advantages over calorie reduction alone.

Low and very low calorie diets

Low calorie diets (LCD, 800–1800 kcal/day) and very low calorie diets (VLCD, < 800 kcal/day) are associated with modest weight loss (5–6%) at 12 months’ follow up. Although VLCD are associated with greater weight loss in the short term (3–4 months), this difference is not sustained at 12 months. These patients require close medical and dietary supervision.

Food composition

High dropout rate and poor compliance with carbohydrate- and energy-restricted diets demonstrated in trial settings suggests that these diets are not widely applicable or acceptable to patients. However, both low carbohydrate (< 30 g/day) and low fat (< 30% of total daily energy) diets are associated with modest weight loss at 12 months. Low carbohydrate/high protein (LC/HP) diets are more effective than low fat/high carbohydrate (LF/HC) diets at 6 months, but the difference between strategies is usually not significant at 12 months. Reduced calorie diets result in clinically meaningful weight loss regardless of the macronutrients they emphasize.

Commercial diets

A variety of commercial weight reduction programmes are associated with a modest reduction in body weight and a reduction in several cardiac risk factors in overweight and obese premenopausal women at 12 months. At 12 months’ follow-up, most commercial diets resulted in a clinically useful weight loss of around 10% in participants who had kept to their original diet, and this was associated with a reduction in hypertension, dyslipidaemia and fasting hyperglycaemia.

Mediterranean diet

There is no consistent definition for the Mediterranean diet and therefore it is impossible to comment on.

Recommendations

In patients with type 2 diabetes, short-term supplementation with omega-3 polyunsaturated fatty acids (PUFA) causes a reduction in triglycerides (TG) but a rise in low density lipoprotein (LDL) cholesterol. It is therefore not generally recommended in people with type 2 diabetes. Vitamin E supplementation is also not recommended in people with type 2 diabetes.

Encouraging dietary change in clinical practice

The use of a behavioural approach to dietary interventions in patients with diabetes leads to clinically significant benefit in terms of weight loss, HbA1c, lipids and self-care behaviour for up to 2 years after the initial intervention.

Intensive therapy or contact in patients with diabetes also leads to clinically beneficial effects on weight and glycaemic control during the period of intervention. More education and contact appears to improve outcomes. Prepackaged meal programmes show significant clinical benefit in terms of weight, blood pressure, glycaemic control and lipids during the study period but are impractical outside the trial setting.

Exercise and physical activity

Smoking

In the general population tobacco smoking is strongly and dose-dependently associated with all cardiovascular events, including coronary heart disease, stroke, peripheral vascular disease and cardiovascular death. In people with diabetes, smoking is an independent risk factor for cardiovascular disease and the excess risk attributed to smoking is more that additive (Table 2.6). Smoking cessation reduces these risks substantially, with the decrease in risk being dependent on the duration of cessation.

Table 2.6 Recommendations regarding diabetes and smoking

Source: American Diabetes Association (2011). Reproduced with permission.

For microvascular disease the evidence is less clear. There is a suggestion that smoking may be a risk factor for retinopathy in type 1 diabetes but not in people with type 2 diabetes.

Those who quit smoking for at least a year experience greater weight gain than their peers who continue to smoke. The amount of weight gained differs according to age, social status and certain behaviours. To prevent weight gain after smoking cessation, individualized interventions, low calorie diets and cognitive behavioural therapy may reduce the associated weight gain without affecting quit rates. Additionally, exercise interventions may be effective in the longer term.

Possible ill effects of smoking include:

Figure 2.1 Deleterious effect of smoking and disease on 10-year mortality. Death rate is expressed as a percentage of that in age- and sex-matched non-diabetic, non-smoking populations.

(Source: Adapted from Bilous and Donnelly (2010). Reproduced with permission.)

Alcohol

Alcoholic beverages are a variable and potentially important component of the diet and may have a bearing on a number of aspects of diabetes (Table 2.7). Alcohol provides energy of 7 kcal/g – almost twice that of carbohydrates and approaching the energy value of fats. Calorie load and risk of hypoglycaemia are the principal concerns.

Table 2.7 Potential relevance of excessive alcohol consumption to patients with diabetes