Asia Pacific J Clin Nutr (1994) 3, 33-39
Asia Pacific J Clin Nutr (1994) 3, 33-39
Body composition in the pathogenesis
and management of diabetes: a Malaysian perspective
Ali Osman* MD, MPH, PhD and B.A.K. Khalid**
MBBS, PhD, FRACP
*Department of Community Health, **Dean,
Faculty of Medicine, 53000, Kuala Lumpur, Malaysia.
There is an increasing prevalence of diabetes mellitus
around the world associated with rapid sociocultural development
and changing lifestyles. Increased prevalence of obesity, with a
higher consumption of animal products and lower consumption of fruits
and vegetables, increases the risk of diabetes mellitus and other
chronic degenerative diseases. Insulin-dependent diabetes (IDD)
is caused by insulin deficiency, whereas the main feature of non-insulin-dependent
diabetes (NIDD) which accounts for more than 90% of diabetics, is
hyperinsulinemia and insulin resistance, which may eventually lead
to actual insulin deficiency. Hyperinsulinemia is undesirable because
it increases the risk of developing vascular disease. In Malaysia,
the prevalence of NIDD in some communities now exceeds 5%, and of
impaired glucose tolerance 10%. Along with these increases in prevalence
of hyperglycemia are increases in prevalence of overweight (BMI>25)
and almost certainly abdominal fatness. In terms of management,
nutrition is given priority. Insulin and hypoglycemic drugs (sulphonylureas
or biguanides), where required, may adversely affect body composition
if overused. Newer therapeutic strategies require greater attention
to the underlying problem in NIDD of abdominal fatness by attention
to the relevant nutritional factors, physical activity and other
lifestyle factors like cigarette smoking and alcohol. The greater
impact of obesity and diabetes on Malaysian women as opposed to
men also needs to be addressed.
Introduction
Diabetes mellitus was described as early as 1600 BC
as a disease with polyuria and insatiable thirst but the detailed
description of the disease and its pathogenesis did not exist until
the nineteenth century. This disease occurs in almost all populations;
however, the prevalence varies depending on the population, its age
structure, genetic background and lifestyle. High prevalences are
found among the Pima Indians in North America, Nauruans, Indians and
Australian Aborigines1 and low prevalence among the Melanesians
in Solomon Islands. Part of the heterogeneity between populations
is probably accounted for by body composition, in turn dependent on
diet, physical activity and substance abuse, over and above genetic
background2. The present report draws on recent observations
of increasing prevalences among Malaysians.
Genetic vs
environmental factors
Community-based studies from Malaysia show that the
prevalence of diabetes is highest among urban Malays and is lower
whe 1000 re the socio-economic development is less (Table 1). However,
urban Malays have lower prevalences of impaired glucose tolerance
(IGT) compared to their rural counterparts. On the other hand, the
prevalence of diabetes mellitus and IGT among Malaysian aborigines
(Orang Asli) is very low in all locations. Certain genetic factors
for the moment probably protect the Orang Asli from the disease, whereas
environmental influences have already increased the prevalence among
genetically susceptible Malays. Community comparisons of fasting,
2 hour post-glucose load and Hb A1 values support an environmental
influence on diabetes occurrence (Table 2).
Table 1. Crude and adjusted prevalence rates
of diabetes mellitus and IGT (per cent)3.
|
Diabetes mellitus |
IGT |
Stages of development
|
crude rate |
age-adjusted* |
95% I** |
crude rate |
age-adjusted* |
95% I** |
Remote
rural |
Lanai (n=110) (ABO)
|
0.0 |
0.0 |
-- |
3.3 |
4.9 |
0.6-17.6 |
Ulu Sungai (n=136) (MAL) |
2.8 |
2.7 |
0.6-8.1 |
14.8 |
15.0 |
8.6-24.0 |
Rural |
Betau (n=136) (ABO) |
1.3 |
1.7 |
0.1-9.5 |
10.7 |
12.6 |
5.9-25.2 |
Koyan (n=132) (MAL)
|
6.7 |
7.4 |
3.0-15.5 |
10.5 |
8.5 |
4.3-15.3 |
Urban |
Lanjan (n=75) (ABO)
|
0.0 |
0.0 |
- |
0.0 |
0.0 |
-- |
Kg. Kerinci (n=92) |
8.2 |
7.7 |
2.9-16.9 |
9.6 |
7.6 |
3.0-16.0 |
ABO = Orang Asli. MAL = Malays. * Five-year age-specific
rates (30-64 years) were calculated and standardization was performed
using the direct method against the standard population of Segi. **
95% confidence interval based on Poisson distribution.
Table 2. Blood glucose and HbA1 by social development3.
Stages of development
|
Fasting blood glucose (mM) |
2 hours post glucose load (mM) |
HbA1 (%) |
Remote rural |
|
|
|
Lanai Aborigines settlement |
|
|
|
N |
111 |
98 |
87 |
means± sd |
5.0± 1.0* |
5.1± 1.7* |
4.5± 0.8* |
Ulu Sungai Malay village
|
|
|
|
n |
152 |
142 |
100 |
means± sd |
5.4± 1.7 |
6.1± 3.2 |
5.5± 1.7 |
Rural |
|
|
|
Betau Aborigines settlement
|
|
|
|
n |
136 |
115 |
74 |
means± sd |
4.8± 0.5** |
5.3± 1.3** |
4.4± 0.5** |
Sungai Koyan Malays
resettlement scheme |
|
|
|
n |
114 |
109 |
78 |
means± sd |
5.1 ± 0.8 |
6.3± 2.5 |
5.6± 1.7 |
Urban |
|
|
|
Lanjan Abongines village
|
|
|
|
n |
73 |
70 |
73 |
means± sd |
5.1± 0.8 |
5.0± 1.2*** |
4.8± 0.6*** |
Kerinci Malays village |
|
|
|
n |
90 |
81 |
89 |
means± sd |
5.3± 1.9 |
6.1± 3.8 |
5.8± 1.8 |
Values are means± sd. *P<0.05 vs remote rural Malays. **P<0.05
vs rural Malays. ***P<0.05 vs urban Malays.
Nutrition
and diabetes mellitus
Various epidemiological studies have shown that a
high consumption of refined carbohydrates and fats, low intake of
dietary fibre, together with obesity and on inactive lifestyle contribute
to the development of non-insulin-dependent diabetes (NIDD)4-6.
Increased per capita energy consumption per day, especially of oils
and fats, animal products and sugar, with a concomitant decline in
the dietary energy from complex carbohydrates such as cereals and
other plant products (pulses, nuts and oilseeds, fruits and vegetables)
are associated with a high risk of developing NIDD. Ingestion of carbohydrates
has not been shown to increase the risk of diabetes except by virtue
of contributing to excessive weight gain7, although there
is interest in partial substitution of carbohydrate with monounsaturated
oils, as in the Mediterranean diet, as a way of minimizing hyperglycemial9a.
Epidemiology
of obesity and diabetes mellitus
Overweight and obesity are important determinants
of NIDD whether in the city or in the village. Data available from
epidemiologic studies and surveys in the USA indicates that 24% of
American women and 22% of men are obese, by criteria of relative body
weight (>120%) or BMI >27.5 kg.m-2. In general, obesity
is common among women from lower socio-economic groups8
and with lower education. The prevalence of overweight and obesity
(BMI ³ 25) in developing countries such as Malaysia
is on an upward trend (Table 3), for urban subjects about 25-30% and
rural subjects 5-15%. The prevalence of diabetes among overweight
Malaysian subjects BMI ³ 25 was 7.3% (9/123) compared to
1.6% (9/560) with BMI <253. Malay females have a six-fold
risk of developing diabetes compared to males, and they also have
a greater prevalence of overweight and obesity.
Table 3. Prevalence of overweight among Malaysians
as indicated by BMI4.
Age groups (years) |
Population |
Number |
Gender |
Criteria of overweight (BMI) (kg/m2) |
Prevalence of overweight |
18+ |
|
|
|
|
|
|
rural Malays |
522 |
male |
³ 25.0 |
5% |
18+ |
rural Malays |
965 |
female |
³ 25.0 |
15% |
25-34 |
Urban executives |
146 |
male |
25-30 |
26% |
35-44 |
of mixed |
209 |
|
|
29% |
45-54 |
ethnicity |
51 |
|
|
33% |
Pathogenesis
of diabetes mellitus
There is a complex interaction between genetic predisposition
and environmental factors in the pathogenesis of diabetes. Diabetes
is not a single disorder but a heterogenous syndrome with varying
pathogenesis. There are broadly two different forms of the disease
type I (insulin-dependent, IDD) and type II (non-insulin-dependent,
NIDD)9. Approximately 90% of diabetics are type II. The
differences in characteristics are shown in Table 4. The development
of type I (IDD) diabetes is based on a chronic, progressive inflammation
of the islet cells (insulinitis) due to the presence of antibodies
against the cells. Hyperglycemia develops because of insulin deficiency
of the B-cells. Environmental factors, possibly including diet are
increasingly regarded as important in the pathogenesis. Type II diabetes
(NIDD) is related to insulin resistance and defective or insufficient
insulin receptors.
Table 4. Comparison between IDD and NIDD.
IDDM (type I) |
NIDDM (type II) |
Prevalence approx 0.2%
Rapid onset of the disease*
Mostly in young age of <40
No frequency difference by sex
Nutritional status - thin
Environmental factors play important roles (viruses or chemicals)
Presence of islet-cell antibodies
Poor insulin production or total deficiency
Absolute insulin deficiency
Good insulin sensitivity
Ketosis prone
No response to sulphonylureas |
Prevalence >3%
Slow onset
Generally onset after age of 40
More frequent in female
Normal or obese
Genetic factors plays important roles
ICA not present
Reduced insulin production or hyperinsulinemia
Insulin resistance or relative insulin deficiency
Poor insulin sensitivity
Ketosis resistant except during infection or stress
Good response to sulphonylureas |
*Although the onset symptoms in IDD is abrupt, its
revolution may involve an antecedent period of slowly developing autoimmune
to the pancreatic B ceils.
Body composition
and NIDD
The prevalence of overweight among people with NIDD
is more than 80%; that of abdominal obesity may even be higher. Individuals
who are 40% overweight have almost a seven times greater chance of
having diabetes mellitus as individuals of normal weight (Figure 1).
Diabetic morbidity also rises as body weight increases7.
The predominant and most characteristic anatomic changes among obese
individuals is the excessive accumulation of adipose tissue or increased
body fat content in certain parts of the body. Determination of overfatness
by skin fold thickness (SFT) and by BMI for total body fatness have
become the most widely used means of assessing body fatness10.
With SFT and truncal circumferences, distribution in body fatness
can also be ascertained.
Fig 1. Incidence of diabetes and body weight
(from Diabetes Source Book, 1969).
Many studies have shown that obesity as indicated
by body mass index (BMI) is significantly associated with incidence
or prevalence of diabetes11-13. Other nutritional indices
such as mid-arm circumference (MAC) and triceps skin fold thickness
(TSFT) subscapular and supralic skin folds (SSSF and SSISFT) also
support the importance of obesity (in particular upper body obesity)
in the development of diabetes. Upper body obesity not only predicts
the prevalence of diabetes mellitus but also IGT (P<0.0001)3.
Abdominal fat distribution in men and women also predicts certain
risk factors of macrovascular disease, such as hypertriglyceridemia
and hypertension. The mechanism by which abdominal fatness increases
the risk for NIDD is not clear. Adipose tissue located in the abdomen
is more sensitive to lipolytic stimuli than adipose tissue elsewhere51.
The lipolytic products, glycerol and free fatty acid (FFA), are directly
delivered to the liver in the splanchnic circulation and enhance gluconeogenesis
and Very Low Density Lipoprotein-Triglyceride (VLDL-synthesis)5l;
FFA also reduce peripheral glucose uptake50; hypertriglyceridemia
increases7.
Fat distribution rather than total fat is a better
predictor for NIDD. Upper body obesity is associated with high prevalence
of NID 1000 D especially among women14-16. Biceps and subscapular
skin fold thicknesses and waist-hip ratio are strongly associated
with NIDD in many studies17-20.
Many obese patients have frank NIDD. They are not
ketosis-prone and do not require exogenous insulin for blood glucose
control. Many other obese patients have IGT. The prevalence in the
community increases strikingly according to lifestyle changes leading
to obesity. However, while obesity may be a very important risk factor
for NIDD, it is and by itself, insufficient to produce this disease.
A genetic susceptibility for NIDD may be necessary for obesity to
induce clinical disease48-49. These are the processes which
now require more intensive study in Malaysian communities.
Body composition
and insulin resistance
One of the metabolic features of obesity especially
upper body obesity is the existence of hyperglycemia in the face of
hyperinsulinemia. This means insulin's ability to influence glucose
metabolism is impaired, a condition referred to as insulin resistance.
With abdominal fatness cells become less sensitive to insulin21
and insulin binding for receptors are reduced22.
Hyperinsulinemia in the presence of normal glucose
tolerance is evident in young people in Pacific Ocean communities
who have high susceptibility to NIDD. Subsequently, insulin resistance
occurs which leads to secondary pancreatic b -cell exhaustion23-27.
The exhaustion leading to an abnormality of insulin synthesis or secretion
may be genetically determined. Both population surveys and prospective
studies of prediabetic Pima Indians indicate that insulin resistance
predates the onset of NIDD28,29. The 'thrifty genotype'
in NIDD could contribute to insulin resistance in muscle. A selective
insulin resistance in muscle would have the effect of blunting the
hypoglycemia that occurs during fasting but would allow energy storage
in fat and liver during feeding. Both of these features could allow
hunter-gatherers to have survival advantages during periods of food
shortage. However, in sedentary individuals allowed free access to
food, these individuals become obese with secondary insulin resistance
in fat and liver. Post-prandial hyperglycemia occurs would then lead
to glucose toxicity with decreased insulin secretion from b -cells30.
Insulin resistance is recognized by diminished response
to endogenous insulin (hyperinsulinemia with normal or elevated blood
glucose concentration) or exogenous insulin (diabetes requiring very
large doses of insulin). Such resistance may be due to changes in
insulin receptors, post-receptor events, or both31. In
obese individuals, the insulin resistance could result from impaired
glucose uptake by peripheral tissues such as skeletal muscle and adipose
tissue, impaired glucose uptake by the liver or increased hepatic
glucose production. However, resistance to insulin action also occurs
in lean individuals with NIDD. Thus it is considered that peripheral
tissue insulin resistance is a characteristic of NIDD and obesity
may not require to produce it27, unless subtle increases
in abdominal visceral fat have not been recognized.
The number of receptors appears to be lower in obese
patients7,13. One theory concerning the development of
insulin resistance in obese NIDD postulates that repetitive postprandial
hyperglycemia initially leads to a down regulation of insulin receptors,
which then results in a compensatory increase in insulin secretion
to prevent glucose intolerance. With more prolonged and greater hyperglycemia,
postbinding defects in insu 1000 lin action then emerge. Decreases
in the intracellular and plasma pools of glucose transporter may occur.
Overt diabetes develops only in individuals whose pancreas is unable
to meet the increased and sustained demand for insulin secretion24.
The cellular mechanism for insulin resistance in NIDD
is still poorly understood. Early reports indicated the inconsistent
relationship between insulin receptor binding and diabetes. However,
more recent reports have found evidence for a postbinding defect in
NIDD. Increased lipolysis in the glucose-fatty acid cycle is partly
responsible for the post-insulin receptor resistance. Insulin resistance
in NIDD is associated with increase in VLDL-TG and decrease in HDLC.
However, whether insulin resistance causes increased VLDL or, conversely,
whether elevations in VLDL impair insulin action, is yet to be determined33.
Hyperinsulinemia and associated insulin resistance
with normal glucose tolerance and not impaired insulin secretion could
be considered as an early phase in the development of NIDD24,34,35.
Progression from normal to IGT is associated with a reduction in insulin
sensitivity. However, glucose tolerance is mildly impaired with a
further compensatory increase in insulin secretion. Syndrome X is
the name given to the association of obesity, hypertension, hypertriglyceridemia,
hyperuricemia and insulin resistance. It is conceivable that abdominal
visceral obesity underlies most of the syndrome, and, in turn, genetic
predisposition to it along with a fatty refined diet and physical
inactivity. If this be the case, then greater attention to the increasing
problem of NIDD, and underlying visceral obesity in Malaysia may have
a useful impact on the Nation's health.
Management
approach
The defective functioning of b -cells and insulin receptors are
difficult to reverse. Therefore, treatment remains symptomatic correction
of the metabolic defects. Exogenous insulin may not be effective due
to a presence of insulin resistance. However, diet, oral hypoglycemic
agents and exercise may be beneficial in obese NIDD23,36-38.
Even so all treatment should be designed to suit individual patients
in relation to ethnic groups' lifestyle, work schedule and education.
Dietary
adjustment
Dietary adjustment to reduce weight is the choice
for obese NIDD patients with insulin resistance. Weight loss results
in an improvement in the metabolic aspects of the diabetic state of
obese individuals with diabetes. In many patients, glucose, lipid,
protein metabolism and insulin secretion and action are restored to
normal. In others, weight loss improves the diabetic state but some
metabolic derangements still persist32. The choice of the
best diet may depend on the degree of obesity and the stage of progression
of b -cell dysfunction39.
A reduced-energy regimen should consist of 50-55%
carbohydrates, 15% protein and 30-35% fats (with a high percentage
of polyunsaturated fats). Obese diabetics will benefit from weight
reduction because reducing body weight actually reduces high glucose
levels to normal (improved glucose tolerance)40. Many obese
NIDD patients, in the earlier stages of diabetes, tolerate weight-maintenance
high-carbohydrate, low-fat diets without deterioration of glucose
tolerance. However, as their insulin reserve declines, high-carbohydrate
diets may further raise glucose levels, so a lower carbohydrate diet
seems preferable. However, in advanced NIDD with deficiency of insulin
secretion, high-carbohydrate diets espe 1000 cially refined carbohydrates
should be avoided39.
Diets which are high in carbohydrate and natural fiber
content produce a lowering of blood glucose as well as a lowering
of low-density lipoprotein cholestrol (LDLC) and triglycerides in
patients with NIDD41. In such patients, glucose homeostasis
improvement is due to increased insulin sensitivity. For obese patients
with diabetes, increased fiber in the diet may also enhance satiety,
thereby aiding in weight reduction. A study carried out in Oxford
found that diets containing a very high proportion of beans (61% carbohydrate,
18% fat, 21% protein and 96.9 g of fibre per day) resulted in the
whole of the glucose profile being lowered41. Delayed absorption
can be achieved by delayed gastric emptying presumably by dietary
fibres or by using 'swelling substances' and slow breakdown of carbohydrates7.
Guar gum and pectin (soluble fibre) was found to delay the absorption
and can be useful in NIDD.
The arteriosclerotic complications found in patients
with diabetes have been attributed partly to elevated plasma lipid
concentrations which are influenced by fat intake. Diets for patients
with diabetes should therefore have reduced fat intake to correct
the unfavourable lipid profile. Achievement of ideal weight, glycemic
control, and when necessary, medical treatment of hyperlipidemias
will retard the process of atherosclerosis. HMG Co-A reductase inhibitor
(pravastatin), and other hypolipidemic agents such as gemfibrozil42,
and bezafibrate reduce cardiovascular risk through the correction
of dyslipidemias43.
Oral
hypoglycemic drugs
Biguanies act to decrease absorption, inhibit gluconeogenesis,
stimulate glucose conversion in muscle and fatty tissue and lower
plasma lipid levels. Their action, therefore, is linked to the presence
of endogenous or exogenous insulin and so they are particularly suitable
for obese diabetics. The side effect of lactic acidosis is probably
less with metformin than other biguanides7.
Sulphonylureas act by stimulating b -cells to release insulin (it depends
upon the existence of b -cells) and helping glucose sensitize the
cells. They are useful for NIDD which cannot be controlled by diet
alone. In NIDD insulin is secreted after stimulation by glucose, but
its secretion is delayed and at low peak. About 30% reduction of blood
glucose level will be produced by using these drugs. Since sulphonylureas
increase insulin secretion, they may be relatively contraindicated
in obese people with diabetes and hyperinsulinism.
Physical
activities
Physical activity improves physical fitness, increases
energy expenditure, helps appetite regulation, favourably influences
serum lipoproteins, lowers blood pressure and, importantly, decreases
the risk of coronary artery disease. Physical training can increase
insulin sensitivity42a. However, the long-term effects
on blood glucose control with exercise alone are not proven. In NIDD,
since the population is often obese and sedentary, exercise would
be expected to have beneficial effects in promoting weight reduction
and thereby improving glucose regulation44. Exercise alone
may have a marked effect on the long-term metabolic abnormalities
of NIDD. But exercise combined with diet that produces greater effects.
Moreover, the weight loss produced by exercising is more easily maintained45,46.
Even through exercise programs may have beneficial
effects for patients with diabet 1000 es in conjunction with diet
or hypoglycemic agents, it is inappropriate to exercise all patients
at the same level of intensity, duration and frequency47.
Weight reduction and sulphonylurea therapy can achieve
a decrease in insulin resistance. Exercise and weight reduction in
obese individuals are accompanied by increased insulin receptor binding
and postbinding insulin actions.
Conclusion
The changing lifestyle, particularly in respect of
fatty, refined diets and decreasing physical activity are likely to
be contributing to visceral obesity, insulin resistance and related
phenomena in Malaysia as elsewhere. Prevention and management of NIDD
require greater research and understanding of these phenomena.
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Nutrition]. All rights reserved.
Please note: this article has been scanned and reformatted.
Please contact lshirven@ozemail.com.au if any errors are suspected.
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February 24, 1999
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