Diabetes

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Chapter 13 Diabetes

Introduction

Type 1 diabetes mellitus (T1DM) — prevalence and incidence

The prevalence of T1DM accounts for about 10% of all cases of diabetes, occurs most commonly in people of European descent and affects more than 2 million people in Europe and North America.1, 2 A recent update reported that in the US the prevalence of diagnosed and undiagnosed diabetes (all forms in all ages as at 2007) totalled 23.6 million people — 7.8% of the population had some form of the disease. That is, those diagnosed accounted for 17.9 million people and undiagnosed 5.7 million people.2

There is also a wide variation in incidence of T1DM from country to country that is evident globally.3 For example, the marked geographic variation in incidence is clearly evident from data that show that a child in Finland has approximately 400 times the likelihood than does a child in Venezuela to acquire the disease.2, 3, 4 Moreover, the incidence of T1DM in children is increasing in Western countries.2, 5, 6 The global incidence of T1DM in children less than or equal to 14 years of age as calculated per 100 000 population has marked variation within ethnic and racial distribution in the world population, as summarised in Table 13.1. The incidence increases with age, highest at 10–14 years of age.

It is not clear from these worldwide variations the factors contributing to the incidence of T1DM but it appears genetics, environmental, dietary and lifestyle factors all play an important role. The reporting of incidence data for T1DM is further affected by possible under-reporting in some regions due to the quality of the registration system used in poorer countries.

There are also further sub-group variations of T1DM incidence within populations.2, 3, 4 For instance, in the US, non-Hispanic white youth have a higher risk of T1DM.2 A multiethnic, population-based study in the United States estimated the incidence of T1DM (per 100 000 person-years) was 24.3 in children (less than 19 years of age) with the highest rate observed in non-Hispanic white youth (18.6, 28.1, and 32.9 for age groups 0–4, 5–9, and 10–14 years, respectively).7

Type 2 diabetes mellitus (T2DM) — prevalence and incidence

As with T1DM the prevalence of T2DM also varies extensively for different populations from distinct geographical areas.8 At the end of the 20th century, it was estimated that 150 million people in the world had diabetes and the World Health Organization (WHO) predicts that, between 1997 and 2025, the number of patients with T2DM will double to reach about 300 million.9, 10 According to the WHO, T2DM affects up to 7% of Western populations and is increasing in newly industrialised and developing countries.11

The ageing of populations and the effects of modernisation of lifestyle have led to a dramatic increase in the prevalence of diabetes globally with very high rates in developing nations, particularly in Asia and the Pacific.

The heightened susceptibility and high prevalence of T2DM of Micronesian and Polynesian Pacific Islanders,10, 12 Native Americans,13 Indigenous Australians and Torres Strait Islanders,10, 14 and Asian Indians14 has been well documented.

In Australia, the prevalence of T2DM has been reported to have doubled since 19816, 10 (Table 13.2).

Table 13.2 Australian prevalence of T2DM

  Men Women
Prevalence 8% 6.8%
Impaired glucose tolerance and/or impaired fasting glucose 17.4% 15.4%

There are a number of risk factors that have been identified with the development of T1DM and T2DM (Table 13.3).

Table 13.3 Risk factors that have been reported to be associated with T1 and T2DM

Risk factors for T1 and T2DM

(Source: adapted from Adamo, Tesson)15

The number of adolescents with T2DM diagnosed yearly is also increasing globally and has been attributed to factors such as weight gain, poor nutrition and lack of exercise.16

Lifestyle — general, education and prevention of T2DM

Intensive lifestyle interventions can reduce the incidence of diabetes in people with impaired glucose tolerance, so encouragement of positive lifestyle strategies is essential where social opportunities arise, such as with school education, religion or in any other social community situations. Lifestyle changes can lead to lifelong changes and reduce the incidence of diabetes or complications associated with diabetes, even after active counselling has ceased.17 A post-intervention follow-up study of participants found the risk of developing T2DM was reduced by 43% over a 7-year median period for those who received intensive lifestyle counselling compared with standard intervention.17

A systematic review and meta-analysis of the literature identified 17 randomised trials of 8084 participants and confirmed the value of intensive lifestyle intervention counselling to prevent and delay T2DM onset in people with impaired glucose tolerance.18 Healthy diet and exercise is much more effective at preventing T2DM than drug therapy. When comparing lifestyle intervention and metformin, a study of 3234 subjects over 3 years with impaired glucose tolerance were randomly assigned to a group of placebo, metformin, or a lifestyle-modification program involving diet and exercise over a 2.8 year follow-up. Lifestyle intervention reduced the incidence of developing T2DM by 58% compared with metformin by 31%.19

The aim of a healthy lifestyle to prevent T2DM:

T2DM is associated with a Westernised lifestyle. Lifestyle management is the most effective way of preventing T2DM, especially with dietary measures and exercise. A recent Cochrane review of the literature emphasises the importance that combined diet interventions and exercise significantly reduces the risk of developing T2DM by up to 37% compared with standard recommendations (RR 0.63) with favourable modest effects on reducing blood lipids and blood pressure compared with exercise or dietary changes alone.20

A study of 577 Chinese adults with impaired glucose tolerance without T2DM from 33 Chinese medical clinics, were randomised to either a control group, or 1 of 3 lifestyle intervention groups that included diet or exercise alone, or diet with exercise over a 6-year period and an assessment of the lifestyle intervention group again in the 20 year follow–up.21

The combined lifestyle intervention group significantly reduced the incidence of developing diabetes by up to 51% over the 6-year period and up to 43% in the 20-year follow-up compared with the control group, and significantly more than the diet and exercise groups alone. This study emphasises the importance of promoting intensive lifestyle changes to prevent diabetes onset, particularly in patients with reported impaired intolerance or at high risk of developing DM.21

Dietary factors and T1DM

Cow’s milk consumption in early infancy

Children fed cow’s milk during the first few days of life are twice as likely to develop T1DM than children who are breast fed.22 The association between T1DM may be explained by the generation of specific immune response to beta casein from cow’s milk exposure, triggering cellular and humoral anti- β casein immune response which may cross-react with beta-cell antigen.23 Overall high cow’s milk consumption (3 or more glasses of cow’s milk a day) was associated with a 5.4 fold increased risk of developing T1DM in young children, and this was higher in children who also had HLA genotype for diabetes.24

Mind–body medicine

Meditation, biofeedback, and hypnosis have all been found to improve T2DM.35

Life stressors and/or depression

Stress may be a contributor to T1DM onset according to a prospective population-based study of almost 6000 children. The study demonstrated children had a threefold risk of developing autoimmunity T1DM if their parents divorced or experienced violence during the child’s infancy within 2.5 years of the event.36 The authors concluded that ‘maternal experiences of serious life events…seem to be involved in the induction or progression of diabetes-related autoimmunity in children’.36 Bullying, a form of stress for a child, is also known to adversely affect glycaemic control and self-management, and increase feelings of depression in T1DM children.37

Research demonstrates that regular use of stress management techniques can significantly reduce blood glucose levels in T2DM. After 1 year, compared with control, stress management reduced HbA1c by up to 1% which is clinically significant. Stress management would be a useful addition to a lifestyle intervention program for diabetics.38

Even daily hot baths for relaxation has been shown to lower fasting serum glucose in diabetics.39 The researchers postulated the benefits could result from increased blood flow to skeletal muscles.

Stress and depression both influence hormonal levels.40 Stress and depression increase cortisol, growth hormone and adrenaline. Cortisol and growth hormone increase insulin resistance, and adrenaline stimulate the breakdown of glycogen into glucose (glycogenolysis).41

Depression is associated with insulin resistance and with diabetes.35 Low mood, mild and moderate depression is 2 to 3 times more common in diabetics than in non-diabetics, and is frequently not diagnosed or treated.42 Insulin resistance is positively associated with the development of diabetes.43 A large prospective scale study of 4847 participants without depression symptoms at baseline, at 3 years, treated T2DM was significantly associated with depression with an odds ratio of 1.52, even after adjusting for BMI, socioeconomic status, lifestyle and diabetes severity, and after excluding T2DM patients on antidepressants possibly for diabetic neuropathy. It was felt that depression contributed to diabetes and diabetes also contributed to depression.44

In another large scale study of more than 4600 patients over 65 years or older, depression symptoms over time was associated with a higher incidence of T2DM after adjusting for other diabetic risk factors.45

In a study of patients with work-related depression, the authors found the presence of depression or depressive symptoms was associated with subsequent increased risk of developing T2DM. The relative risk was 1.25 (95% confidence interval [CI]:1.02–1.48) compared with workers not experiencing depression.46

There is a positive correlation between insulin resistance and severity of depressive symptoms with impaired glucose tolerance before the outbreak of T2DM.47

A recent study found that serotonin receptor agonists can improve glucose tolerance, and reduce plasma insulin levels.48

Hence, the proper management of depression and stress are key factors in reducing the risk and progression of diabetes (see also Chapter 12).

Sunshine and Vitamin D

Vitamin D deficiency plays an important role with both insulin synthesis and secretion by way of vitamin D receptors and vitamin D binding proteins in pancreatic tissues as demonstrated in both human and animal models. The mechanism of action of vitamin D is also thought to occur as a direct action on pancreatic beta-cell function and mediated through regulation of plasma calcium levels, which may explain why vitamin D deficiency may play a role in the causation in T1 and T2DM.49

Lack of sunshine exposure is contributing to vitamin D deficiency as most vitamin D forms in the skin as a result of ultraviolet radiation (UVB wavelength; 290–320 nm) exposure from sunlight.50

People living in the southern regions of the southern hemisphere or the northern regions of the northern hemisphere have a higher risk of vitamin D deficiency, particularly during the winter months. Certain ethnic groups are at increased risk of vitamin D deficiency, especially dark skinned people who cover their skin for religious or cultural reasons, the elderly, babies of vitamin D deficient mothers, and people who are housebound or are in institutional care.51

Food sources for vitamin D include oily fish, eggs, and meat or fortified foods such as margarine and some milk products. However, food sources make a relatively small contribution to total vitamin D status (less than 10%).

Environment

Physical activity

Physical activity is one of the key modifiable risk factors for hyperglycaemia. Evidence from population-based, cross-sectional studies report that both decreased physical activity and elevated sedentary behaviours, such as television viewing time, are independently associated with raised blood glucose levels in adults without a diagnosis of diabetes.62, 63 Regular exercise benefits T1DM and T2DM. Children with T1DM showed improved haemoglubin A1c (HbA1c) and glycaemic control with regular exercise of at least 3 times weekly compared with children who did not exercise.64, 65

Walking just 30 minutes daily can significantly reduce the incidence of T2DM.66 Walking 2 hours weekly can reduce mortality from all causes by 39% and by 34% from cardiovascular disease in patients with T2DM.67 A study of healthy young sedentary men demonstrated a high intensity aerobic exercise protocol comprising a total of 15 minutes of exercise (6 sessions; 4–6 30-second cycle sprints per session) substantially improved insulin action and glucose tolerance test, and supported the important role of exercise in preventing diabetes.68

The size of cities can influence the risk of diabetes. When a person migrates from a rural environment or third-world country to the city or a Western country the risk of T2DM is significantly elevated.69, 70 If that city happens to be of more than 1 million in population, as described in a recent study,69 then the risk of diabetes increases fourfold. It is thought that the design of cities can influence whether the people walk or not.

The position statements from both the American Diabetes Association and the American College of Sports Medicine, has recommended the use of resistance training as part of a physical activity program to reduce the risk of developing diabetes.71, 72

A Cochrane meta-analysis of 14 randomised controlled trials (RCTs) comparing exercise against no exercise in 377 participants with T2DM found that compared with control and independent of weight loss, exercise intervention significantly improved glycaemic control as indicated by a significant decrease in glycated haemoglobin levels of 0.6% (−0.6% HbA1c, 95%CI −0.9 to –0.3; P < 0.05), reduced visceral adipose tissue, plasma triglycerides but not cholesterol levels.73

Of interest, studies indicate aerobic and resistance training alone improves glycaemic control in T2DM, but improvements were greatest with a combined exercise training of both aerobic with resistance training.74

Tai chi

Tai chi is a Chinese system of slow meditative physical exercise designed for relaxation, balance and health. Tai chi has demonstrated improved balance, gait speed, muscle strength, cardiorespiratory fitness, and quality of life in older adults.7580

However, recent studies including a systematic review have demonstrated that there is some controversy as to its efficacy for patients with T2DM.81

Recently reported RCTs have demonstrated a change in fasting blood glucose levels.7982 One RCT demonstrated no significant intergroup differences in fasting blood glucose levels compared with a placebo intervention.83

One Chinese clinical trial84 reported superior effects of tai chi on fasting blood glucose levels compared with walking or running, while 2 other Chinese clinical trials85, 86 reported that there was no difference compared with a self-management program, or no treatment.

Three clinical trials reported assessing the effectiveness of tai chi on HbA1c.83, 84, 85 Of these only 1 RCT85 suggested no effectiveness of tai chi on HbA1c compared with a sham exercise regimen whereas 2 Chinese clinical trials83, 84 failed to report intergroup differences compared with no treatment, self-management, walking or running exercise activities. One recent Chinese clinical trial with women diagnosed with T2DM reported that the tai chi group had significantly improved glycaemic control and serum triglyceride levels.86

Yoga

There are few studies that have investigated the efficacy of yoga in T2DM.

Three small studies from India have demonstrated and suggested that yoga asanas and pranayama can better manage glycaemic control and stabilise autonomic functions in T2DM cases.91, 92, 93 Moreover, in 1 of these studies it was reported that yoga improved sub-clinical neuropathy.93

A recent community-based study of yoga classes for T2DM aimed to demonstrate benefits of yoga for diabetic patients but unfortunately experienced ‘recruitment challenges; practical and motivational barriers to class attendance; physical and motivational barriers to engaging in the exercises; inadequate intensity and/or duration of yoga intervention; and insufficient personalisation of exercises to individual needs’ and these factors need to be considered in any future research.94 It also highlights how research in yoga can be difficult.

A systematic review of the literature identified 25 eligible studies, including 15 uncontrolled trials, 6 non-RCTs and 4 RCTs. Overall, the studies demonstrate yoga showing benefit in several risk indices, including ‘glucose tolerance and insulin sensitivity, lipid profiles, anthropometric characteristics, blood pressure, oxidative stress, coagulation profiles, sympathetic activation and pulmonary function, as well as improvement in specific clinical outcomes’.95 Again, the authors acknowledge the limitations of these studies when drawing firm conclusions and encourage additional high-quality trials to confirm the benefits of yoga in diabetics.95

Diet and nutrition

For both Type 1 and Type 2DM, a low-GI diet can ‘improve glycaemic control in diabetes without compromising hypoglycaemic events’ according to a recent Cochrane review of the literature of 11 relevant RCTs involving 402 participants, although no study reported on mortality, morbidity or costs.96 Low glycaemic diet led to a significant decrease in the glycated haemoglobin A1c (HbA1c) and less episodes of hypoglycaemia compared to high GI diet.96

T2DM

A low GI diet is as effective as medication in improving glycaemic control in diabetics. Patients with T2DM should be under the care of a dietician or diabetic educator to continually monitor their diet. Dietary compliance is fundamental in the management of T2DM.100

A recent study has reported that in those individuals that are at risk for developing T2DM a change in lifestyle that includes dietary manipulation with a significant decrease in fat intake and a concomitant increase in vegetable and fruit consumption resulted in marked inhibition of the transition from the pre-diabetic state to manifest T2DM.40

It has been documented that a diet rich in wholegrains and seafood will be high in magnesium.41, 101

There is a strong inverse relationship to T2DM with magnesium.102 Also, such diets may be protective against the development of T2DM.103 Wholegrain intake is inversely associated with homocysteine and markers of glycaemic control, and studies suggest a lower risk of diabetes and heart disease in persons who consume diets high in wholegrains.104

Foods rich in soluble fibre such as oats, legumes, guar gum and psyllium are more slowly absorbed and produce lower blood glucose levels.105 Increasing dietary fibre up to 50g daily (such as raisins and oranges) can improve glycaemic control in patients with T2DM.106 There is increasing evidence that inflammation plays an important role in the pathogenesis of diabetes, as obesity is associated with a pro-inflammatory state.107

A Cochrane review that investigated the potential effects of wholegrain foods for the prevention of T2DM has concluded that studies have consistently demonstrated that a high intake of wholegrain foods or cereal fibre is associated with a lower risk of the development of T2DM.108 However, the evidence for a protective effect coming from prospective cohort studies only has to be considered as weak as with this design no cause and effect relationship could be recognised. Hence, it was further concluded that well-designed RCTs are warranted that are able to draw definite conclusions about the preventive effects of wholegrain consumption on the development of T2DM.108

Other food considerations

Vegetarian, plant-based diet

A review of the literature demonstrates a strong link between vegetarian and plant-based diets in reducing the risk of obesity, T2DM, heart disease and some cancers.125 A diet high in vegetables and vegetarianism can significantly reduce the risk of diabetes, improve glycaemic and lipid control and reduce cardiovascular complications.126, 127

Body weight

Obesity is the main predisposing risk factor for the development of diabetes.128

The prevalence of obesity varies among different racial groups and it is associated with approximately 30% of Chinese and Japanese patients with T2DM. Obesity is found in 60–70% of people in Western countries and, although estimates vary, it is thought that the prevalence of T2DM could be as high as 30% of aboriginal people.129 Pima Indians, Pacific Islanders from Nauru or Samoa will all almost certainly develop T2DM with obesity.130

In a study of 1079 participants, intensive lifestyle intervention for overweight patients with impaired glucose tolerance reduced the 3-year incidence of overt T2DM from 35% to 15% by losing 5 kg compared with the control intervention. Every 1 kg of weight loss resulted in a relative risk reduction of developing TSDM by 16%.131

A number of dietary regimes have been recently reported as alternatives for macronutrient intake and the prevention of chronic diseases.132 A comparative study that included the macronutrient contents of 7-day menu plans from the Omni-Heart Study, Dietary Approaches to Stop Hypertension (DASH), Zone, Atkins, Mediterranean, South Beach, and Ornish diets were evaluated for consistency with the US Food and Nutrition Board’s Acceptable Macronutrient Distribution Ranges and with the dietary recommendations of several health organisations for the prevention of cardiovascular disease, cancer and metabolic syndrome. The intent of the study/analysis was to evaluate the healthfulness of the 3 Omni-Heart Trial diets high-carbohydrate (Omni-Carb), high-protein (Omni-Protein), and high unsaturated fat (Omni-Unsat) diets — and were compared with that of the DASH diet and 5 other popular diets, namely the Atkins, Ornish, South Beach, Mediterranean, and Zone diets. The resultant analysis reported that all 3 Omni study diets were consistent with US national guidelines to reduce chronic disease risk. Further, that, popular diets vary in their nutritional adequacy and consistency with guidelines for risk reduction.132

There is also significantly strong evidence that special diets can substantially reduce the risk of developing T2DM.

The Mediterranean diet

The Mediterranean diet with its emphasis on vegetables, grains, fish and olive oil has been shown to reduce the risk of atherosclerosis in diabetic patients.133, 134 There is a significant amount of evidence that strongly suggests that the Mediterranean diet could serve as an anti-inflammatory dietary pattern.135 This could help prevent diseases that are related to chronic inflammations that include visceral obesity, T2DM and the metabolic syndrome.135 The rationale for this evidence is further supported by a recent study that demonstrates that adherence to the Mediterranean diet is inversely associated with risk of developing diabetes and the clustering of hypertension, diabetes, obesity, and hypercholesterolemia among high-risk patients.136, 137

Monounsaturated fatty acids (MUFA) — olive oil and nuts

The MUFA (especially olive oil) in the Mediterranean diet appear to play an important preventative role for T2DM, even in healthy subjects. Insulin sensitivity reduced in healthy subjects on diets high in MUFA compared with diets high in saturated fatty acid. Subjects with the Ala 54 allele of the fatty acid-binding protein 2 gene demonstrated improved insulin sensitivity when the saturated fats were replaced by the MUFA.137

High content of MUFA found for instance in the Mediterranean diet may explain the preventative role in reducing insulin resistance leading to T2DM.

A large prospective cohort study involving over 83 000 university graduates without diabetes at baseline demonstrated high adherence to the Mediterranean diet with an 83% reduced risk of developing T2DM.138

Consumption of nuts and peanuts is related inversely with diabetes risk.139 Nuts may also confer cardiovascular benefit and improve lipid profile for patients with T2DM due to their high content of MUFA and nutritional value.140

After 6 months of adding 30g of walnut to a low-fat diet of T2DM patients, compared with those on no walnuts, the LDL cholesterol dropped by 10% and HDL cholesterol increased.141

(Refer to Table 13.4.)142

Table 13.4 Healthy fats for diabetics’ monounsaturated fats

Oils and margarines Vegetables Nuts
Polyunsaturated fats:
Oils and margarines Fish and other seafood Nuts and seeds
Canola, olive, macadamia, sunflower oil, peanut Avocados, olives Almonds, peanuts, cashews, hazelnuts, macadamias, pecans
Sunflower, safflower, corn, soybean, sesame, cottonseed, grapeseed, flaxseed oil or linseed

Walnuts, pine nuts, brazil nuts, sesame seeds, sunflower seeds, flaxseed or linseed

(Source: adapted from Phillips & Carapetis.)142

Nutritional supplements

Vitamins

Antioxidant micronutrients may play a role in the prevention of diabetic complications.154

Multivitamin/mineral supplements

Elevated C–reactive protein levels have been associated with the risk of cardiovascular disease and T2DM. An analysis of the data from a randomised, double-blind, placebo-controlled study was carried out at the end of the trial and it was reported that multivitamin use was associated with lower C–reactive protein levels.172 Recently, it was demonstrated in an RCT that the effects of vitamins C and E, and also when in combination with magnesium and zinc, were a significant improvement of glomerular, but not tubular, renal function in T2DM patients.173 Furthermore, in randomised placebo-control trials after 3 months of using the combined multivitamin and mineral supplements, the treatment group had significant increased HDL cholesterol and apolipoproteins (apo) A1 enzyme levels, and reduced blood pressure in T2DM patients but no change in serum levels of total cholesterol, LDL cholesterol, triglyceride, and apo B levels. This suggests that the multivitamin and mineral supplements may have a favourable cardiovascular benefit by raising HDL levels and reducing blood pressure in T2DM. Supplementation with vitamin C and E and Zn when used alone did not show any benefit.174, 175

Other studies have not been able to demonstrate any benefit of antioxidants on fasting blood glucose levels in T2DM.176

Middle-aged and elderly patients with T2DM experienced a significant reduction of infections such as flu-like illnesses respiratory, gastrointestinal and urinary tract infections, and days off work (17% of diabetics) in those who took a daily multivitamin supplement compared with those who took placebo (90% of diabetics).177 Researchers postulated patients with diabetes were more likely to have suboptimal intake of micronutrients which would explain the positive effect.

Diabetics should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources.

Minerals

Chromium

Chromium has been the most widely studied supplement for diabetes as it is essential for the metabolism of glucose and blood lipids by the body. Low levels of chromium are associated with increased risk of T2DM.178

Numerous in vitro and in vivo studies suggest that chromium supplements, particularly niacin-bound chromium or chromium-nicotinate may be effective in attenuating insulin resistance and lowering plasma cholesterol levels.179 Chromium functions as a co-factor for insulin, regulating the activity of insulin. It has been reported that T2DM patients, who are chromium-deficient, are likely to benefit from chromium supplementation.180189

A recent review has concluded that there was no significant effect of chromium on lipid or glucose metabolism observed in people without diabetes.190 However, chromium supplementation significantly improved glycaemia among patients with diabetes.190 A further review reported that there was greater bioavailability of chromium picolinate compared with other forms of chromium, such as niacin-bound or chromium trichloride. This may explain the comparative superior efficacy in glycemic and lipidemic control.191 The pooled data from the studies that were investigated that used chromium picolinate supplementation for T2DM patients demonstrated substantial reductions in hyperglycaemia and hyperinsulinemia, which then equates to a significant reduced risk for disease complications.191

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