complications: estimates and projections to the year 2010. Diabet Med 1997; 14: S7, S85.
Nutritional Management of Cardiac Risk Factors inType 2 Diabetes AUDREY BRYNES Hammersmith Hospital, London, UK
INTRODUCTION
In people with diabetes three out of four deaths are caused by cardiovascular disease (1).
There is a three- to fivefold increase in myocardial infarction (MI), with an increase up to 10, 15-fold once diabetic neuropathy develops.
Angina and left ventricular failure are common, while interventions such as angioplasty and coronary artery bypass grafting have worse outcomes in people with diabetes compared with non-diabetic people (2).
Thus the management of Type 2 diabetes is largely about addressing cardiovascular risk factors.
The vast majority of people with Type 2 diabetes have associated insulin resistance which is now recognised as the key pathophysiological defect.
INSULIN RESISTANCE SYNDROME
Reaven, at his Banting Lecture in 1988 (3), first proposed a widespread role for insulin resistance in common diseases such as coronary heart disease, Type 2 diabetes, obesity and hypertension.
He proposed an insulin resistance syndrome (IRS) (or Syndrome X) as a unifying theory for a cluster of adverse metabolic changes (Table 9.1).
Each of these changes have been independently shown to be related to a risk of cardiovascular disease.
Insulin resistance is also a strong marker for the risk of developing Type 2 diabetes and therefore a
Nutritional Management of Diabetes Mellitus. Edited by G. Frost, A. Dornhorst and R. Moses & 2003 John Wiley & Sons, Ltd. ISBN 0 471 49751 7
134 NUTRITIONAL MANAGEMENT OF DIABETES MELLITUS
Table 9.1 Metabolic and related disorders associated with the insulin resistance syndrome
Glucose metabolism Hyperinsulinaemia Glucose intolerance Lipid metabolism Hypertriacylglycerolaemia (particularly elevation of VLDL-TG and VLDL-apolipoprotein B) Exaggerated postprandial lipaemia Decreased HDL-cholesterol concentrations (particularly HDL2-cholesterol) Preponderance of small dense LDL-cholesterol particles Other Hypertension Increased coagulation (PAI-1) Central obesity Increased body flux of non-esterified fatty acids (particularly impaired postprandial suppression) Clinical correlates Cardiovascular disease Type 2 diabetes Gout Breast cancer Source: Adapted from Reaven (4).
reduction in insulin resistance is a key goal which may delay the onset of Type 2 diabetes.
Thus dietary advice to reduce insulin resistance (or increase insulin sensitivity) is essential.
IRS affects lipid metabolism as well as carbohydrate metabolism.
Alterations in the lipid profile, as described in Table 9.1, are at the centre of the insulin resistance syndrome (4).
This cluster of risk factors is commonly seen in the presence of obesity, which is thought to contribute to the development of both Type 2 diabetes and increased cardiovascular risk.
In Europe, modest improvements in CHD mortality have occurred during the last two decades (5).
It is likely that some of this reduction in CHD mortality is a result of health strategies first introduced in the 1960s that targeted modifiable CHD risk factors.
These included discouraging smoking, treating hypertension and lowering cholesterol concentrations.
Despite modest falls in the non-diabetic population, no improvement in CHD has occurred within the diabetic population (6).
PRESENCE OF INSULIN RESISTANCE BEFORE THE ONSET OF TYPE 2 DIABETES It is interesting to note that although the incidence of people with diabetes in the UK is thought to be around 5%, the number of people with insulin
NUTRITIONAL MANAGEMENT OF CARDIAC RISK FACTORS 135
resistance is nearer 25% (7).
There are strong genetic determinants for the development of insulin resistance.
The offspring of people with Type 2 diabetes have been shown to be more insulin resistant than those with no family history and this relationship is independent of obesity (8).
Non-diabetic first-degree relatives of people with Type 2 diabetes also have similar thrombotic risk clustering to their diabetic relatives (9).
In 1990 Haffner et al. (10) theorised that macrovascular complications start to develop very early on, initiated by insulin resistance and/or hyperinsulinae- mia in the prediabetic state, whereas microvascular complications develop after sustained hyperglycaemia.
In the Quebec heart disease study high fasting insulin concentrations were reported to be an independent predictor of ischaemic heart disease in men (11).
However, a meta-analysis of a prospective population-based cohort and case-controlled studies, reported by Ruige et al. in 1998 (12), found a weak relationship between plasma insulin levels and CVD, suggesting that other risk factors, such as lipids, must also be involved.
NOT JUST FASTING LIPIDS BUT POSTPRANDIAL LIPID CONCENTRATIONS
Only 50% of CHD is explained by traditional risk factors such as smoking, hyperlipidaemia, hypertension and diabetes. This may be because most risk factor assessments and many public health campaigns have focused on fasting lipid levels as their main criteria rather than diets to reduce many of the postprandial metabolic disturbances attributed to insulin resistance. Much of the current work in this area is investigating the role of lipids in the postprandial state.
OBESITY AND INSULIN RESISTANCE
Obesity is the most common condition associated with insulin resistance (13).
Obesity is a health problem reaching epidemic proportions in Western countries.
In the UK alone some 16% of men and 18% of women are obese (14).
Obesity can be defined as a body mass index (BMI) greater than 30 kg/m2.
Insulin resistance is frequently observed in obese subjects and constitutes an independent risk factor for the development of Type 2 diabetes and atherosclerosis.
The importance of increasing visceral fat (measured by waist:hip ratio) as a risk factor for insulin resistance and cardiovascular disease has also been demonstrated (15).
Weight loss improves insulin sensitivity and any type of therapy, whether it is dietary or pharmacological, that can aid effective weight loss and/or weight maintenance will help prevent some of the deleterious metabolic changes associated with insulin resistance.
136 NUTRITIONAL MANAGEMENT OF DIABETES MELLITUS
SUMMARY OF DISTURBANCES AT A CELLULAR LEVEL IN INSULIN RESISTANCE At a molecular level cellular factors have been identified that can markedly influence insulin action either directly or indirectly.
These include tumour necrosis factor (TNF) a, glucose transporters (GLUT) and peroxisome proliferator activated receptor (PPAR)g, while increased glucose flux has been shown to induce insulin resistance in skeletal muscle.
For a more detailed review see Garvey and Birnbaum (16).
There is also likely to be a genetic predisposition to insulin resistance (17).
Current treatments of Type 2 diabetes have little impact on reducing insulin resistance and this may explain why treating diabetes has only marginal benefits on reducing CHD mortality.
It is hoped that with the introduction of thiazolidinediones, a novel class of oral agents that reduce insulin resistance, this may change.
Environmental influences on insulin sensitivity are not yet completely understood.
Exercise has a strong beneficial effect (18) and obesity a strong adverse effect.
The effects of diet on insulin sensitivity are discussed later.
DYSLIPIDAEMIC LIPID PROFILE Patients with Type 2 diabetes have an abnormal lipid profile with high levels of LDL-cholesterol and triglycerides (TG) and a low level of HDL- cholesterol.
Data from the Multiple Risk Factor Intervention Trial (MRFIT) (19) suggest that although levels of total cholesterol and LDL- cholesterol do not differ significantly between patients with and without diabetes, those with diabetes have higher concentrations of atherogenic small dense LDL-cholesterol particles.
A few years ago effects on TG were seen as largely irrelevant, as it was thought that the relationship between TG levels and CHD was weak.
However fasting plasma TG concentrations have recently been demonstrated to be an independent risk factor for the development of CHD (20).
In a meta-analysis of 17 population-based studies, TG concentrations were particularly important in relation to CHD risk, where a 1 mmol/l increase in plasma TG increased cardiovascular risk by 32% in men and 76% in women.
DIETARY MANIPULATION
While diet is the mainstay of therapy for people with Type 2 diabetes, the ideal dietary guidelines remain unsettled. Current recommendations aim to promote good glycaemic control and maintain ideal body weight while reducing the risk of CHD through improved lipid profiles. These are very much in line with the
NUTRITIONAL MANAGEMENT OF CARDIAC RISK FACTORS 137
recommendations of the Committee on Medical Aspects of Food (COMA) on diet and cardiovascular disease.
In addition to this there is a move away from defined macronutrient prescription and a move towards the treatment of risk factors in the context of lifestyle, behavioural and individualised changes that the patient is willing and able to make.
Cultural and ethnic background should be taken into account.
The Stanford group led by Reaven, as well as groups led by Katan, Grundy and Willet have argued for many years that guidelines for CHD and diabetes should be changed from the historic high-carbohydrate/low-fat diet philoso- phy.
They recommend lowering the carbohydrate level and increasing energy from monounsaturated fats which do not demonstrate the postulated detrimental effects of carbohydrate on TG (21).
FAT AND INSULIN SENSITIVITY Himsworth first made the association between increased dietary fat and insulin resistance in the 1930s and since then much has been published on these effects.
In a recently published review on the subject by Storlien et al. (22), the premise was developed that the type of fatty acids eaten may be as important as the quantity of fat in the diet.
High-fat diets, particularly high saturated fat, are associated with the development of Type 2 diabetes and glucose intolerance, while the intake of long-chain fatty acids, in particular n-3 fatty acids, seems protective.
In addition the San Luis Valley Diabetes Study found that high saturated fat and low starch and fibre intakes were associated with hyperinsulinaemia in a non-diabetic population (23).
It has also been demonstrated, using the euglycaemic hyperinsulinaemic clamp method, that increased monounsaturated fat improves insulin sensitivity and glycaemic control while having no adverse effects on lipids (24,25).
The mechanism for this is uncertain (26).
FAT AND PLASMA LIPIDS A high intake of saturated fatty acids has been associated with an increased incidence of CHD, presumably because a high saturated fat intake increases LDL-cholesterol and reduces HDL-cholesterol (27). The lipid-lowering effects of monounsaturated fatty acids (MUFAs) compared to n-6 polyunsaturated fatty acids (PUFAs) are well studied, suggesting that PUFAs may be more potent at lowering plasma LDL- cholesterol and TG (27). There is accumulating evidence in the literature that increasing the percentage of total energy contribution from MUFA fat has a positive effect on lipids as well as improving glycaemic control in people with Type 2 diabetes.