Vildagliptin may be a better treatment
option than repaglinide for Type 2 diabetes in patients who also
have symptomatic coronary artery disease (CAD), research
suggests.

Presenting her findings at a poster session at the American
Diabetes 70th Scientific Sessions in Orlando, Florida, USA, Rosa
Rahmi, from the University of Sao Paulo in Brazil, explained that
her team had found repaglinide was more likely to eliminate
ischemic preconditioning (IPC), which protects against myocardial
necrosis, in these patients than vildagliptin.

IPC refers to the “phenomenon in which short periods of
myocardial ischemia promote resistance to a subsequent ischemic
insult,” she said.

The cellular pathways underlying this phenomenon appear to
involve the ATP-potassium channel.

Rahmi and team sought to investigate the effect of two
hypoglycemic agents - vildagliptin and repaglinide - on IPC in 83
patients with Type 2 diabetes and a positive exercise test, who
also had multivessel coronary disease confirmed by coronary
angiography.

Of these patients, 42 were receiving repaglinide 2 mg and 41
were receiving vildagliptin 100 mg.

Five days before the study started, nitrates, calcium entry
blocking agents, beta blockers, angiotensin-converting enzyme
inhibitors, angiotensin II receptor blockers, and sulfonylurea
drugs were withdrawn.

The participants completed phase I, which involved two
sequential exercise treadmill tests (T1 and T2), with a 30-minute
gap, while not taking hypoglycemic agents. They then took the
hypoglycemic agents for a week and completed phase II involving
another two sequential exercise treadmill tests (T3 and T4).

All the patients experienced ischemia (1.0-mm ST-segment
depression) during each of the exercise tests. IPC was demonstrated
by an increase in the time to the onset of ischemia between T1 and
T2.

In phase II, however, 83% of patients taking repaglinide
experienced ischemia significantly earlier in T4 than in T3 (298
seconds vs 337 seconds, respectively), indicating the cessation of
IPC. In comparison, cessation of IPC occurred in just 28% of
patients taking vildagliptin, while 72% preserved the protective
effect.

The researchers propose that IPC might be diminished by
repaglinide because it exerts its effects by binding to the
sulfonylurea receptor, which regulates ATP-potassium channel
activity.

Vildagliptin, on the other hand, is a dipeptidyl peptidase-4
inhibitor and so exerts its glucose-lowering effects through the
interaction of glucagon-like peptide 1 with a specific receptor
located on the cell membrane of the pancreatic beta cells.

The researchers concluded that because vildagliptin did not
affect IPC in a “relevant way” in patients with Type 2 diabetes and
CAD, it may be a “good alternative treatment in this
population.”

They call for further studies to determine the mechanisms
underlying this protection.

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Meeting website

There is a strong association between the
metabolic syndrome and microvascular disease in people with Type 2
diabetes, Belgian researchers have shown.

Their analysis, which appears in the journal Diabetes &
Metabolic Syndrome: Clinical Research & Reviews, suggests
that the risk for microvascular complications increases in line
with both the presence and severity of the syndrome.

Michel Hermans (Universite catholique de Louvain, Brussels)
and team studied 738 adults with Type 2 diabetes, of whom 145 had
the metabolic syndrome. Participants with and without the syndrome
were well-matched with respect to age and diabetes duration.

The mean number of components of the metabolic syndrome was 1.8
in those without the syndrome versus 4.0 in those with.

Body mass index, waist circumference, relative/absolute fat
mass, visceral fat, conicity, insulin resistance, triglycerides,
glycated hemoglobin, systolic blood pressure, and inflammatory
markers were all significantly higher in those with versus without
the metabolic syndrome.

With regard to macrovascular disease, the prevalence of
peripheral artery disease, coronary artery disease, and
cerebrovascular disease were all higher in those with the syndrome
than without, at 11 vs 7%, 26 vs 10%, and 8 vs 5%,
respectively.

Furthermore, the prevalence of microvascular complications
increased with increasing number of components of the metabolic
syndrome.

Specifically, diabetic retinopathy affected 3% of those with one
component versus 26% of those with five components. For peripheral
neuropathy the values were 19% and 35%, respectively, while for
albuminuria the values were 6% and 32%, respectively.

Discussing their results, Hermans and co-authors note that the
association with macrovascular disease is expected “as intrinsic to
the current definition of metabolic syndrome.”

By contrast, “it is much debated whether establishing the
presence of a metabolic syndrome in hyperglycemic states further
contributes to stratifying or predicting microvascular risk.”

They say their data “indicate a strong association between
metabolic syndrome and vascular disease, with respect to both
macro- and microangiography in a large, mostly Caucasian, cohort of
Type 2 diabetes mellitus patients of both genders.”

However they add: “Whether these risks are cumulative,
potentiating or permissive will be determined in prospective
studies on the natural history of microvascular disease in relation
with the serial acquisition of metabolic syndrome phenotype
components.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Free abstract

Routinely collected patient data can
accurately predict cardiovascular disease (CVD) risk in people with
Type 2 diabetes across a range of ethnicities, New Zealand
researchers believe.

Writing in Diabetes Care, the team says that renal
function, ethnicity, and glycemic control are important risk
factors and “should be included in locally relevant CVD risk
equations used to make treatment decisions in people with
diabetes.”

C Raina Elley (University of Auckland) and co-workers developed
the new CVD risk score using data from the New Zealand Diabetes
Cohort Study (DCS). The DCS is an ongoing prospective open-cohort
study that is collecting data from a national, annual, primary-care
screening program.

The score was developed using data on 36,127 individuals with
Type 2 diabetes and without CVD. Their median age was 59 years, 51%
were women, 55% were of non-European ethnicity, and 33% had
albuminuria.

During a median follow-up of 3.9 years there were 6479 first CVD
events, giving a 5-year observed risk of 20.8%. Cox proportional
hazards regression models identified four significant independent
risk factors for CVD: Glycated hemoglobin, the presence of
microalbuminuria, and Indo-Asian or Maori ethnicity.

These factors were then incorporated into a new “DCS risk
equation”, which also included age, gender, duration of diabetes,
systolic blood pressure, smoking status, ratio of total cholesterol
to high-density lipoprotein cholesterol, ethnicity, glycated
hemoglobin, and albumin-to-creatinine ratio.

Elley’s team then validated these factors using data on 12,626
individuals living in a different region of the country. The DCS
risk equation had an area under the receiver operating
characteristic curve (C-statistic) of 0.68 for predicting 5-year
CVD risk and 0.69 for predicting 5-year CHD risk.

The new equation consistently underestimated risk by 1-5%, say
the authors. However, it compares favorably with the Framingham and
United Kingdom Prospective Diabetes Study equations, which have
C-statistics of 0.63 and 0.63, respectively.

The authors conclude: “Renal function, glycemic control, and
ethnicity are important risk factors and should be included in
locally relevant CVD risk equations used to make treatment
decisions in people with diabetes.

“More accurate risk prediction may improve the quality of care
received, avoid delays in treatment for those in whom risk was
previously underestimated, and may thus help address inequalities
in health outcomes.”

MedWire (www.medwire-news.md) is an independent clinical news
service provided by Current Medicine Group, a trading division of
Springer Healthcare Limited. © Springer Healthcare Ltd;
2010

Free abstract