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Insulin Resistance - Journal of Complementary Medicine - 2006

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acute & chronic insulin resistance
> acute & chronic

Insulin
resistance
Diabesity, the ‘lifestyle disease’ of the 21st century, is now biting epidemiologically.
It begins with a metabolic dysfunction that is preventable with diet and lifestyle
strategies, as Christine Houghton outlines.

D
isordered glucose metabolism is pandemic in the
Christine Houghton, BSc, GradDipHumNutr, DipAAM, is a
industrialised world.1 Type 2 diabetes, the ultimate
practising clinical nutritionist and a complementary-medicine
effect of prolonged insulin resistance (IRS), has a
industry consultant
worldwide prevalence exceeding 200 million and is
predicted to rise to over 300 million in the next 20 years. Sig-
The Editor thanks Gary Deed, MBBS, DipHerbMed, FACNEM,
nificantly, someone, somewhere, loses a leg every 30 seconds
Medical Director, YourHealth Carina and President of Diabetes
of every day due to diabetic complications.2
Australia (Queensland); and Prof Trish Dunning, Director
Australians may appropriately fear death from heart attack,
Endocrinology and Diabetes Nursing Research, Department
paralysis from stroke or amputation from accidental injury, but
of Endocrinology & Diabetes, St Vincent's Hospital (Melbourne)
many are not aware that type 2 diabetes is the likely forerunner
Ltd, for their kind assistance in the peer review of this article
of many cases of these fatal or disabling conditions. Likewise,
they may not realise that terms such as ‘insulin resistance’ and
‘metabolic syndrome’ are life-threatening conditions in evolu-
tion. Even less well understood is the fact that the progression
from IRS to diabetes is not inevitable. Lifestyle modification is
a key factor in altering disease progression.3

Insulin resistance and diabetes

Insulin resistance refers to a prediabetic state where adipose
and muscle cells in particular do not respond optimally to the

26 Complementary Medicine November / december 2006


Diabetes in Australia –
The AusDiab follow-up, 20055
• Every day in Australia, approx. 275 adults develop
diabetes (more than 100,000 new cases per year)
• More than 200,000 people progress from overweight circulatory failure, nephropathy, retinopathy and
to obesity each year
• Every year, 400,000 adults develop hypertension
• Every year, 270,000 adults develop kidney disease. factors apparent in individuals, rather than just as a
The risk is higher in females and older people
• The percentage of people developing diabetes between
1999–2000 was twice as high for those who did no
physical activity compared to those who undertook
more than 150 minutes per week of physical activity
• People with prediabetes (elevated blood-glucose levels
science photo library.com
but not as high as for diabetes) were 15 times more
likely to develop diabetes than were those with normal
blood-glucose levels
• Obese people were four times more likely to develop
diabetes than were those with normal weight
hormone insulin. As a consequence, the pancreas compensates
by secreting additional insulin (hyperinsulinaemia) in an at-
tempt to ‘force’ the insulin receptors on cells to allow glucose
uptake. In some cases, fasting glucose is higher than normal or
impaired (IFG); in others, the two-hour post-prandial blood
glucose is also elevated but not to diabetic levels, which is
known as impaired glucose tolerance (IGT).
Significantly, a long period of IRS, during which the
blood-glucose levels are maintained at near-normal levels by
compensatory hyperinsulinaemia, precedes overt type 2 dia-
betes. When pancreatic beta–cells can no longer compensate
for IRS, IGT occurs. Without intervention, IRS is likely to
progress to overt diabetes.4
In Australia, the recently published AusDiab Phase 25
study presents the five-year follow-up data on 6000 Austral-
ian adults whose baseline data were collected in 1999–2000.
AusDiab Phase 2 provided benchmark national data on the
prevalence of diabetes, obesity, hypertension and renal disease
in Australia [see ‘Diabetes in Australia’ box].
Professor Paul Zimmet, Director of the International Dia-
<
acute & chronic
• Insulin resistance (IRS) is currently in epidemic
proportions, with a high likelihood of progression
to type 2 diabetes
• Approximately 50% of type 2 diabetics are unaware
they have the disease and remain undiagnosed
• IRS and type 2 diabetes lead to serious complications
that may include cardiovascular disease and
blindness, neuropathy and poor wound healing
• Health professionals are urged to treat each of the risk
single syndrome
• Health professionals are typically reluctant to broach
weight loss with patients but are urged to treat the
overweight condition in the context of diabetes risk
and not simply on cosmetic grounds
• A number of metabolic pathways are implicated in the
pathophysiology of IRS. Emerging evidence shows that
oxidative stress is considered to lie at the core of the
initial defect
• Oxidative stress may play a common role in linking
pancreatic beta–cell dysfunction, endothelium
dysfunction and damage in other tissues (such as
retinal and renal) incapable of regulating glucose
influx to the cell
• The roles of superoxide, peroxynitrite, nitric oxide and
uric acid are all implicated in diabetic complications.
Therapies to target superoxide anion as the initial
reactive oxygen species are being researched
• Although more research is required, there is
preliminary evidence that many nutrients and herbals
are effective as a complement to appropriate dietary
and lifestyle advice
• Many clinicians use the American Diabetes Association
dietary guidelines as a basis in individualising
programs for patients; many incorporate glycaemic-
index and glycaemic-load principles
betes Institute and Professor of Diabetes at Monash Univer-
sity, said the AusDiab findings sent a ‘red alert’ to ordinary
Australians and those responsible for public health. He added
that ‘with 275 cases of type 2 diabetes and 600 cases of obesity
occurring every day, we now have compelling proof that Aus-
tralia’s diabetes epidemic is in full flight’.6
November / december 2006 Complementary Medicine 27
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acute & chronic insulin resistance

Defining the problem Metabolic syndrome

Health authorities are rightly concerned and have included dia- Dr Gerald Reaven, Emeritus Professor of Medicine at Stanford
betes as one of Australia’s six current National Health Priority University, California, is credited with popularising the term
areas. Diabetes causes almost as much disability burden as it ‘metabolic syndrome’ in 1988.15 Reaven’s definition described
does mortality burden.7 The magnitude of the problem is ap- the cluster of cardiovascular risk factors linked to IRS and obes-
parent when one considers that the prevalence of type 2 diabe- ity. Most notably, the definition included the coexistence of
tes in Australia has more than doubled since 1981. Approxi- obesity, type 2 diabetes, hyperlipidaemia and hypertension.
mately one in four Australian adults has either type 2 diabetes This risk-factor clustering and its association with IRS led
or impaired glucose metabolism.8 In fact, the World Health investigators in the late 20th century to propose the existence
Organization (WHO) showed in 1994 that 30 per cent of those of a unique pathophysiological condition, the ‘metabolic’ or
with IGT developed type 2 diabetes within three years.9 Type 2 ‘insulin resistance syndrome’.16 Reaven postulated that IRS
diabetes is often considered a ‘lifestyle’ condition of affluent na-
and the resultant compensatory hyperinsulinaemia predis-
tions such as Australia because more than two-thirds of adults posed patients to hypertension, hyperlipidaemia and type 2
with this form of diabetes live in developed countries.10 diabetes and thus was the underlying cause of much cardio-
vascular disease (CVD). While Reaven’s definition did not in-
The prediabetic state clude obesity in the list of primary disorders, he acknowledged
The term ‘prediabetes’ is used to describe the group of indi- that it too was correlated with IRS or hyperinsulinaemia and
viduals whose glucose dynamics leaves them at strong risk of suggested the obvious treatment for what he termed ‘Syn-
developing type 2 diabetes within the near future. Prediabetes drome X’ was weight management and physical activity.
is defined as either: Since 1988, the definition and even the existence of such a
syndrome has been hotly debated. Much of the uncertainty and
• IGT, where fasting glucose is <7.0 mmol/L and two-hour ambiguity exists because leading experts and organisations use
plasma glucose level is >7.8 mmol/L and <11.1 mmol/L; or different criteria to define the cluster of factors that predispose in-
• IFG of 6.1–6.9 mmol/L and two-hour glucose of <7.8 mmol/L. dividuals to CVD. The WHO and the National Cholesterol Ed-
ucation Program Adult Treatment Panel (ATP-III) are two such
A number of studies show the progression from prediabetes to influential organisations whose definitions are subtly different
type 2 diabetes can be substantially delayed or prevented by im- [see ‘Which metabolic syndrome definition is that?’ table].
proving diet and increasing physical exercise. Lindahl indicated As is apparent from comparing both sets of data, there are
in 2005 that lifestyle change induces a multitude of beneficial sufficient differences between the two that it is likely some pa-
metabolic effects that may protect against cardiovascular disease tients will be included and others excluded from either defini-
and type 2 diabetes. However, these beneficial metabolic effects tion. Nevertheless, it is obvious that the term ‘metabolic syn-
only persist as long as the lifestyle regimen is maintained.11 drome’ is now accepted in the medical literature. That aside,
In Australia, an estimated 50 per cent of type 2 diabetes the Joint Statement of the American Diabetes Association and the
cases are currently undiag- European Association for the
nosed.12 Therefore, a system Study of Diabetes clearly rec-
to identify this substantial ‘at
The WHO emphasises the significance of ommends that, until much-
risk’ group is an important impaired glucose tolerance and fasting glucose, needed research is completed,
public-health priority. Indeed, clinicians should evaluate
in 2003 Shaw and Chisholm
stating that ‘Lifestyle interventions appear and treat all CVD risk factors
outlined the extent of the generally more effective than medications’ without regard to whether a
problem and summarised patient meets the metabolic-
the Australian clinical guidelines.13 They concluded that GPs syndrome diagnostic criteria.19 In short, using inappropriate
could contribute to prevention by lifestyle advice and screening, definitions to classify ‘at risk’ individuals means some patients
which was indicated in everyone aged over 55 and in younger will remain unidentified and inappropriately treated.
people with risk factors such as obesity, hypertension, family Reaven and other authors have stressed the need for clinicians
history or certain ethnic backgrounds. to address individual CVD risk factors irrespective of whether
The WHO emphasises the prognostic significance of IGT the metabolic-syndrome criteria are met. In addition, Shaw and
and IFG, and stated that, ‘In general, lifestyle interventions Chisholm state that, ‘Type 2 diabetes has now been recognised as
appear to be more effective than medications’.14 one manifestation of the “metabolic syndrome”’.20

28 Complementary Medicine November / december 2006


insulin resistance acute & chronic
Which metabolic syndrome definition is that?
Criterion ATPIII definition17
Any 3 or more of the following:
Waist measurement Circumference
Males 102 cm
Females > 88 cm
Serum triglycerides ≥ 1.7 mmol/L
HDL cholesterol Males < 1.0 mmol/L
Females < 1.3 mmol/L
Blood pressure ≥135/85 mmHg
Serum glucose ≥ 6.1 mmol/L (≥ 5.6 mmol/L may be applicable)
Urinary albumin-excretion rate
Markers for identifying insulin resistance
High levels of overweight and obesity in the community cor-
relate with IRS or frank diabetes, however, it is important to
realise that not all overweight people are insulin resistant. A
simple method of determining which overweight individu-
als are likely to be insulin resistant would be clinically useful.
Research indicates clinicians are often reluctant to provide
weight-loss counselling for overweight patients.21 Clinicians
might be more likely to offer weight-management advice
if obesity could be directly correlated to prediabetes. Read-
ily accessible pathology data without the need for a two-hour
OGTT provides a number of useful correlates. Two facts need
to be considered:
1. Plasma triglyceride (TG) and HDL cholesterol are inde-
pendently associated with IRS and are both independent
predictors of CVD.22 Jeppesen et al in 2001 investigated
the relationship between these two parameters in 2906 men
aged between 53 and 74 who were without clinical evidence
of coronary artery disease at baseline. They followed the
men for eight years, measuring lipid fractions, BP, smoking
status and physical-activity levels.23 After adjusting for oth-
er risk factors, including LDL, the researchers concluded
that 35 per cent of ischaemic heart disease might have been
prevented in those subjects with the lowest TG and highest
HDL-C levels. In other words, a low TG:HDL ratio can be
one indicator of CVD protection, even when other risk fac-
tors are present.
2. Plasma ratio of total cholesterol to HDL cholesterol
(TC:HDL) is a well-recognised predictor of CVD and is
also highly correlated with IRS.
<
WHO definition18
Diabetes, IFG, IGT or IRS (assessed by OGTT) and ≥ 2
of the following:
Waist–hip ratio
Males > 0.9
Females > 0.85
≥ 1.7 mmol/L or abnormal HDL as below
Males < 0.9 mmol/L
Females < 1.0 mmol/L
≥140/90 mmHg
Any measurement related to IRS
20 mcg/min or an albumin:creatinine ratio of ≥ 30 mg/g
Which overweight patients should be targeted?
McLaughlin et al suggested that the TG:HDL ratio correlates
with the likelihood of IRS and those who are overweight are
more likely to exhibit CVD risk factors than those who are not
insulin resistant.24 Because the insulin suppression test, the
‘gold standard’ for diagnosing IRS, is not practical to adminis-
ter under clinical conditions, three easily measured parameters
are used to identify overweight insulin-resistant patients at
greatest risk of CVD: triglyceride levels, TG:HDL levels and
fasting insulin concentration.
Reaven stressed in 2005 that the TG:HDL ratio has similar
sensitivity and specificity to the plasma insulin concentration.25
In addition, the relationship between low HDL and CVD risk
makes the TG:HDL ratio a useful clinical marker of CVD risk
and IRS. The study showed that 50 per cent of the overweight
individuals were in the most insulin-resistant tertile.
Identifying insulin-resistant individuals is clearly an im-
portant means of identifying overweight patients most likely
to be at risk of CVD.
Other researchers26 have reached the conclusion that the
TG:HDL ratio positively correlates with IRS in severely obese
non-diabetic individuals. Interestingly, the ratio does not cor-
relate for people with frank type 2 diabetes.
Clinicians reluctant to address weight-loss issues can use
the TG:HDL ratio as a surrogate marker of IRS. Rather than
having to order a specific test such as a GTT in the first in-
stance, the need for further investigation can be determined
using the data available on the patient’s standard E/LFT. If the
TG:HDL ratio is outside normal range, the the need for the
oral GTT can be justified. A positive result on the oral GTT
then makes it much easier to address the sensitive topic of
November / december 2006 Complementary Medicine 29
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acute & chronic insulin resistance
weight loss. A weight-management program is then easily jus-
tified on medical grounds and not for cosmetic reasons.
Therapeutic strategies
While the lowering of blood-glucose levels to as close to nor-
mal as possible is the main goal of therapy, it is of interest
to note that at least one study demonstrated that improving
glycaemic control through lifestyle intervention in type 2 di-
abetes had a more beneficial effect on adipokine levels than
lowering of HbA1c by the same degree with insulin therapy.27
This unexpected finding might have occurred because adipose
tissue is no longer regarded as a mere fat storage depot; it is
now considered as an endocrine organ that produces a range
of biologically active substances: the adipokines including lep-
tin, TNF–alpha, adiponectin, interleukin–6 and resistin.28
Simple caloric restriction has been shown to reduce the
generation of reactive oxygen species (ROS) by limiting the
degree of activity through the mitochondrial electron-trans-
port system. Caloric restriction therefore has the direct benefit
of inducing weight loss in insulin-resistant individuals, as well
as inhibiting the extent of ROS activity and the consequent
adverse effects on endothelia and the pancreatic beta–cells.
Dietary intervention
It would appear that the dietary management of glucose-reg-
ulating disorders is a highly controversial topic, with many
clinicians at odds with the mainstream position established
largely by the American Diabetes Association (ADA). Holistic
practitioners in Australia have been selectively recommending
30 Complementary Medicine November / december 2006
supplements for decades and many incorporate the glycaemic
index/load principles as part of their dietary advice to patients.
Although the ADA maintains that sucrose need not be unnec-
essarily restricted in diabetics, holistic clinicians would argue
that sugar represents ‘empty calories’ and, as such, tends to de-
plete those nutrients required for its own metabolism.
Diabetes Australia takes its lead largely from the ADA. The
ADA’s ‘Nutrition Principles and Recommendations in Diabe-
tes’ provides what it describes as evidence-based principles for
medical nutrition therapy. Its recommendations are presented
by evidence levels and the following table [see p 33] summa-
rises its key recommendations.
Under a section on ‘Special Considerations for Type 2 dia-
betics’, the ADA stresses the need for regular aerobic exercise
as a means of lowering glucose. Although it makes no men-
tion of smoking, one would assume that frequent reference to
‘lifestyle modification’ would include tobacco avoidance.
The relationship between obesity and IRS is well document-
ed29, as is the fact that weight loss will usually improve insulin
sensitivity. Bessessen argued that increased energy intake may
be the nutritional factor most responsible for obesity and IRS.30
Energy restriction, independent of dietary composition, may be
the best nutritional approach to treating IRS. In addition, di-
etary saturated fat appears to be associated with IRS. However,
Bessessen claimed that although low-GI diets may ultimately
prove beneficial, their use remains controversial.
Just what dietary advice an insulin-resistant individual
should be given is therefore uncertain. While many clinicians
have embraced low glycaemic index (or glycaemic load; see JCM
2004;4(2):35–8) concepts, the ADA does not endorse such ad-
vice.31 Recent (2004) ADA guidelines state that, ‘In subjects
with Type 2 diabetes, studies of 2–12 weeks’ duration compar-
ing low glycaemic index and high glycaemic index diets report
no consistent improvements in HbA1c, fructosamine or insulin
levels’. Nevertheless, many clinicians continue to advise patients
according to the principles of glycaemic index and glycaemic
load, given that implementation of such advice is unlikely to
have any adverse effects. Patients following this approach fre-
quently report being less inclined to snack between meals.
A number of studies have shown that replacing some of
the dietary carbohydrate and saturated fat with isocaloric
amounts of monounsaturated fats, primarily olive oil, is ben-
eficial. A meta-analysis revealed that high-monounsaturated-
fat diets improve lipoprotein profiles as well as glycaemic con-
trol32, and there is no evidence that they induce weight gain.
Interestingly, the ADA guidelines state, ‘high-monounsatu-
rated fat diets have not been shown to improve fasting plasma
or HbA₁c’. Likewise, Luscombe et al demonstrated that high-
mono/high-GI, or high-CHO/low-GI intake, more effectively
 >
acute & chronic insulin resistance
reduces HDL than high-CHO/high-GI diets but have no ef-
fect on glucose metabolism.33
In 2005, Reaven stressed that low-fat/high-CHO diets do
not modify the basic defect in IRS and accentuate all of its met-
abolic manifestations.34 He did not advocate substituting satu-
rated fat for carbohydrate because replacing saturated fat with
mono- or polyunsaturated fats reduces LDL-C concentrations
without any of the adverse metabolic effects associated with
low-fat/high-CHO diets. Reaven’s recommendation differs to
that given by the ADA, which advises that saturated fat can be
substituted with either carbohydrate or monounsaturated fats.
Several papers point to the value of the Mediterranean diet
[see JCM 2005;4(6):51], with its focus on monounsaturated
fats, as a model for cardiovascular management. This approach
is well accepted by most patients as being palatable, convenient
and satisfying. There is no epidemiological evidence to suggest
that it has any adverse effects and, because many of the compli-
cations of diabetes are cardiovascular in nature, it can provide a
dietary model that would appear to satisfy the criteria.
Nutritional supplementation
A number of nutrient supplements are widely self-selected or
recommended by Australian clinicians to manage glucose dys-
regulation. These include various anti-oxidants, magnesium
and chromium as micronutrients, as well as herbal prepara-
tions. It is not known definitively just how effective these non-
standardised medications are but anecdotal evidence would
suggest that continued usage may indicate positive benefit.
It would be reasonable to assume that because the superox-
32 Complementary Medicine November / december 2006
ide free-radical anion is implicated in the pathogenesis of vascu-
lar complications, the therapeutic application of dietary or sup-
plemental anti-oxidants in people with type 2 diabetes might
be beneficial. Serum carotenoids are inversely associated with
type 2 diabetes and impaired glucose metabolism. Coyne et al
undertook a cross-sectional survey of 1600 individuals from six
randomly selected Queensland cities in 2000 to investigate this
association and found that the higher the carotenoid intake, the
lower the dysfunction in glucose metabolism.35
However, administering the anti-oxidant vitamin E to dia-
betic subjects failed to show beneficial effects on diabetic com-
plications.36 The researchers concluded the failure was due to
the mechanism by which vitamin E scavenges already-formed
oxidation products and its inability to scavenge early enough
in the free-radical cascade.37
Considerable research shows that superoxide overproduc-
tion may be the primary event triggered by hyperglycaemia,
suggesting that strategies to target superoxide may slow the
abnormal biochemical processes that lead to diabetic compli-
cations.38 Ceriello used compounds that act as superoxide
dismutase (SOD) mimetics that are said to be equivalent in
action to SOD enzymes. This strategy alters the course of the
disease by limiting adverse endothelial effects.
Continuing this line of thinking, it is possible that other com-
plications such as retinopathy, neuropathy and nephropathy are
related to excessive superoxide production that leads to compro-
mised function in these tissues. Anti-oxidants that are capable of
upregulating the SOD enzyme may have a clinical role in protect-
ing diabetics against these debilitating complications.
In addition, there have been a number of studies on other
supplements for which the evidence is encouraging.39 Some of
the more significant of these are discussed below.
Chromium — significant benefits exist for a role for chro-
mium in glucose, insulin and lipid metabolism in humans,
with dietary intake being generally inadequate.40 While several
studies41,42 show benefits in enhancement of glucose metabo-
lism at doses of 200–250 mcg/day, other studies show no ben-
eficial effect. Another review paper43 of chromium in IRS con-
cluded that chromium picolinate is the most efficacious form
with demonstrated safety. Supplements of 200–1000 mcg/day
have been shown to enhance glycaemic control.
A recent study44 demonstrated that 1000 mcg/day of chro-
mium picolinate over two months in five obese subjects with
polycystic ovarian syndrome — in which IRS is a predomi-
nant feature — improved glucose disposal.
Lipoic acid — preliminary clinical studies in people with
type 2 diabetes showed acute enhancement of insulin-stimu-
lated glucose disposal after 600–1000 mg alpha–lipoic acid.45
My own clinical experience continues to reaffirm the positive
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insulin resistance acute & chronic

American Diabetes Association Nutrition Principles and Recommendations31

Nutritional factor A-level evidence B-level evidence Expert consensus

Carbohydrates • Foods containing CHO from whole
(CHO) grains, fruits, vegetables and low-
fat milk should be included in a
healthy diet
• Total CHO is more important than
source or type
• Sucrose does not increase
glycaemia more than isocaloric
amounts of starch. Sucrose need
not be restricted
• Non-nutritive sweeteners are safe
when consumed as directed
• Low-GI CHO foods may reduce
postprandial hyperglycaemia but
there is not sufficient evidence to
recommend use of low-GI diets as a
primary strategy in meal planning
• Dietary fibre is recommended but
there is no requirement to increase
intake above that of people without
diabetes
• CHO and monounsaturated fat
should provide a combined 60–70%
of energy intake
• Consider the need for weight
loss when recommending
monounsaturated fat
• Sucrose should be consumed in
the context of a healthy diet

Protein • Ingested protein does not increase
plasma glucose in people with type
2 diabetes, even though protein
stimulates insulin as potently as
does CHO
• No evidence that usual protein
intake (15–20% energy) should be
modified if renal function is normal
• Long-term effects of high-protein,
low-CHO diets are unknown. Effect
of such diets on LDL is of concern

Fat • <10% energy should be saturated
fat. With high LDL, consider
lowering to <7%
• Dietary cholesterol should be <300
mg/day or less
• To lower LDL, replace saturated fat
with monounsaturated fat or CHO
• Minimise trans fats
• Include 2–3 fish meals per week
• Reduced-fat diets give modest
weight loss

Energy balance • Reduced energy and modest weight

loss improve insulin resistance and
glycaemia
• Long-term weight loss requires
lifestyle change and increased
physical activity
• Standard weight-loss diets are
unlikely to produce weight loss

Alcohol intake • Limit to 1 standard drink for women

and 2 for men per day
• Consume alcohol with food to limit
hypoglycaemia

Micronutrients • No clear evidence for benefit from

vitamin and mineral supplements
• Routine anti-oxidant
supplementation not advised due to
uncertainties related to long-term
efficacy and safety

November / december 2006 Complementary Medicine 33

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acute & chronic insulin resistance

benefit in relieving the symptoms of peripheral neuropathy at limited data.54 Nevertheless, gymnema is a popular remedy
levels of 400–600 mg lipoic acid daily, although blood-glucose amongst Australian practitioners, who use it to assist in gly-
levels may be unchanged. caemic control and to suppress sugar cravings.
Magnesium — It would appear that low serum magne- Bitter melon (Momordica charantia) is considered to have
sium is a strong independent predictor of incident type 2 dia- positive preliminary results.55 Bitter melon, however, can in-
betes.46 Human studies47 show that supplementation with 2– duce potassium depletion, so caution is warranted.
4.5 g/day magnesium raised plasma magnesium and improved Fenugreek (Trigonella foeniculum-graecum) is a Mediter-
short-term glucose handling and insulin response, and these ranean legume with a long history of use as a herbal medicine
levels may not be achievable by diet alone. 500–1000 mg/day [see JCM 2005;4(5):77–80]. Just 15 g/day of ground fenugreek
is recommended to reduce BP and arrhythmias.48 seeds have been shown to lower postprandial glucose levels.56
Potassium — hypokalaemia from any cause induces IRS, However, fenugreek is known to confer an unpleasant odour to
hyperglycaemia and hypertension.49 There is a strong implica- individuals who take it regularly. Fenugreek used today thera-
tion here for patients to ensure optimum intake of fresh fruits peutically is more likely to be of an odour-free concentrated ex-
and vegetables. tract. In this case, 1 g/day has been shown to improve glycaemic
Ascorbate is usually low intracellularly in people with dia- control and decrease IRS.57 Most trials using fenugreek, how-
betes.50 Vitamin C is essential to reduce glycoslyation of pro- ever, are uncontrolled but the evidence suggests further studies
teins, block aldose reductase (which affects vision) and improve may be warranted.
endothelial dysfunction but has no effect on glucose levels. Ginseng (Panax quinquefolium) — most published trials of
ginseng, albeit limited in number, appear to use the American
Herbal supplementation ginseng variety. In an eight-week Finnish study58 of 36 type 2
Numerous herbs and vegetables have been shown to affect diabetic subjects, a 200 mg dose of P. quinquefolium was shown
glucose regulation. All traditions of herbal medicine — espe- to elevate mood and improve psychophysical performance as
cially Ayurvedic, Chinese and Western — report on herbs that well as to reduce fasting blood glucose HbA1c levels.
modulate glucose. Many of these herbs, such as cinnamon [see Other hypoglycaemic herbs — a systematic review54 re-
JCM 2006;5(5):67–9], rosemary and bitter melon have culi- fers to several plants with evidence of positive glycaemic ef-
nary applications, while others have a tradition of medicinal fects. These plants are ivy gourd (Coccinia indica), garlic (Al-
use only. While clinical trials are few, there is sufficient evi- lium sativum), onion (A. cepa), holy basil (Ocimum sanctum),
dence to encourage further large-scale studies. The following pata-de-vaca (Bauhinia fortificata) and pedra hume caa (Myr-
have some reportable level of evidence. cia uniflora), fig leaf (Ficus carica), milk thistle (Silybum mari-
Cinnamon — several trials using Cinnamomum cassia or C. anum), Aloe vera and prickly pear (Opuntia streptacantha).
verum show favourable effects on glucose dynamics in multiple There are several combination herbal formulations in the
ways. In a study of 60 people with diabetes, doses of 1, 3, and 6 Chinese and Tibetan traditions that show encouraging results;
g daily for 40 days reduced fasting glucose 18–29 per cent, trig- however, there appears to be only one trial for each combina-
lycerides by 23–30 per cent tion, making objective evalu-
and LDL cholesterol by 7–27 One gram per day of fenugreek seeds has ation difficult.
per cent.51 The authors com- The ADA acknowledges
ment that this quantity can been shown to improve glycaemic control and the potential clinical value of
be readily incorporated in the decrease insulin resistance, while 15 g/day has herbals in glycaemic control
diet and need not necessarily but urges physicians to be cau-
be consumed as a supplement. lowered postprandial glucose levels tious about combining these
A more recent trial on post- with prescribed medication
menopausal women using 1.5 g/day for six weeks has failed to [for more on potential interactions, see JCM 2006;5(1):71–7].
replicate these findings.52 However, a trial has been subsequently In summarising the role of dietary supplements in diabetes,
published that involved 79 patients with type 2 diabetes. These the ADA59 lists anti-oxidants, various minerals, trace minerals
patients supplemented with 3 g/day cinnamon powder for four and herbal preparations and concludes that ‘there is no clear
months. It observed a moderate effect in reducing fasting glucose evidence of benefit from vitamin or mineral supplementation
concentrations, particularly in those with higher baseline levels.53 unless deficiencies can be demonstrated’. Similarly, it suggests
Gymnema sylvestre — the scientific evidence is consid- that, although several herbal preparations have shown mild ben-
ered to be suggestive but inconclusive in diabetes, given the efit, ‘there is no evidence to suggest long-term benefit from such

34 Complementary Medicine November / december 2006

 <
insulin resistance acute & chronic

preparations and there may exist the potential for interaction
with prescribed medication’. In many of these studies, although
the outcomes were positive, the trials used few subjects, making
their findings inconclusive. Many researchers recommend fur-
ther studies.
Since so many insulin-resistant or diabetic patients are over-
weight or obese, there are likely to be micronutrient deficien-
cies present. Because adipose tissue generates inflammatory
cytokines, it is advisable to provide appropriate dietary modi-
fication or supplementation to counter inflammation and the
resultant increase in oxidative stress. Omega–3 fatty acids and
anti-inflammatory herbs, such as curcumin, may here be of ben-
efit although though they won’t alter glucose regulation directly.
Orally bioavailable superoxide dismutase may also be of assist-
ance in this context.
Conclusion
Because of the uncertainties in defining the ‘metabolic syn-
drome’, clinicians are advised to treat each of the risk factors
as separate entities rather than as a syndrome. Several surrogate
markers of IRS simplify the process of identifying which over-
weight individuals are likely to be prediabetic. Clinicians can
more appropriately address weight-loss management in the ‘at
risk’ patients.
At the biochemical level, a number of metabolic path-
ways appear to play a role in the pathophysiology of IRS as
a forerunner to type 2 diabetes. Several research groups have
hypothesised that oxidative stress lies at the core of the initial
defect and may play a role in pancreatic beta–cell dysfunction
as well as endothelium dysfunction, and damage other tissues
incapable of regulating glucose influx to the cell.
The roles of superoxide, peroxynitrite, nitric oxide and uric
acid are all implicated in the chain of events that lead to the
development of diabetic complications. Therapies to target su-
peroxide anion as the initial ROS are being researched. Studies
using compounds that can experimentally inhibit superoxide
have been shown to be very useful.
Appropriate dietary advice for IRS and type 2 diabetes is
difficult to establish since the research findings are conflicting.
The Mediterranean diet and the ADA diet, with additional
recommendations based on glycaemic index or load, appear to
be clinically effective. ◗

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