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Type 2 diabetes causes excessive morbidity and premature
cardiovascular (CV) mortality. Although tight glycemic control
improves microvascular complications, its effects on macro-
vascular complications have been mixed. In the ACCORD
study, tight glycemic control was associated with increased
CV and all-cause mortality, despite a significant reduction in
non-fatal myocardial infarction (MI). Some diabetes medica-
tions like the glitazones and saxagliptin (a DPP-4 inhibitor)
have been associated with an increase in the risk of hospital-
ization for heart failure, despite improving glucose control.
In the recent EMPA-REG OUTCOME study conducted in
patients with type 2 diabetes at high cardiovascular risk,
treatment with empagliflozin (an SGLT2 inhibitor) was asso-
ciated with impressive reductions in CV/all-cause mortality
and also hospitalization for heart failure without any effects
on classic athero-thrombotic events (MI and stroke). Equally
impressive was the effect of empagliflozin on renal outcomes.
Compared to placebo, empagliflozin treatment was asso-
ciated with a 39% relative risk reduction in the occurrence of
incident or worsening nephropathy, defined as progression to
macroalbuminuria, doubling of serum creatinine, initiation of
renal replacement therapy, or death due to renal disease. Of
note, these cardio-renal benefits occurred in the setting of
more than 80% of the patients being on statins and ACEi/ARB
agents. However, what is puzzling about the above CV and
renal benefits is the fact that the curves for heart failure
hospitalization, renal outcomes and CV mortality begin to
separate within 3 months and were maintained for more than
3 years. It is unlikely that modest improvements in glycemic,
lipid or blood pressure control contributed significantly to the
beneficial cardio-renal outcomes within three months.
Other known effects of SGLT2-inhibitors on visceral adiposity,
the vascular endothelium, natriuresis and neuro-hormonal
mechanisms are also unlikely major contributors to the
cardio-renal benefits. We postulate that that the cardio-renal
benefits of empagliflozin are due to a shift in myocardial and
renal fuel metabolism away from fat/glucose oxidation, which
are energy inefficient in the setting of the diabetic heart
and kidney and towards an energy efficient
“
super
”
fuel like
ketone-bodies which improve myocardial/renal work effi-
ciency and function. Even small beneficial changes in ener-
getics on a minute-to-minute basis translate into large
differences in efficiency and improved cardio-renal outcomes
over weeks to months and continue to be sustained. Well
planned physiologic and imaging studies need to be done to
characterize this
“
fuel energetics
”
based mechanism for the
cardio-renal benefits.
Lunch Seminar
–
Zespri
LN15-1
Kiwifruit
–
A double agent for glycaemic control and nutrient
enhancement
John MONRO
1
.
1
The New Zealand Institute for Plant & Food
Research, New Zealand
A ripe kiwifruit is a luscious, sweet, carbohydrate-rich food
–
the kind of food that would be expected to raise blood glucose
concentrations. However, kiwifruit is also nutrient dense and
capable of promoting health in numerous ways.
We therefore faced two questions:
1. What is the true glycaemic potency of whole kiwifruit
–
the capacity of the whole fruit to raise blood glucose?
2. What effect does the interaction of kiwifruit with other
components of a meal have on the meal
’
s glycaemic
impact?
We addressed these questions in a research sequence
involving in vitro and human intervention studies, and found:
(a) The non-digested dietary fibre remnants from kiwifruit
that had been digested in vitro occupied about four times
their original volume in the intact fruit. They would
therefore surround and extensively interact with other
foods in the limited volume of the gut.
(b) Within the dispersion of pre-digested kiwifruit remnants
several processes important to the glycaemic response
were substantially retarded in vitro, including:
•
Digestion
•
Sugar diffusion
•
Mixing of intestinal contents
(c) In a human intervention study we found the glycaemic
impact of kiwifruit to be relatively low; 100 g of kiwifruit
would have about the same effect on blood glucose as only
6 g of glucose.
(d) The low in vivo glycaemic impact could be partly
attributed to the carbohydrate in kiwifruit being fruit
sugars, but the kiwifruit also caused changes in the
blood glucose response curve that indicated improved
homeostatic blood glucose control due to factors other
than sugar, consistent with effects of kiwifruit remnants
on intestinal processes indicated by the in vitro studies
above (in c).
(e) Analysis of the effects of equal carbohydrate, partial
substitution of kiwifruit for highly glycaemic foods
–
such as those based on cereal starch
–
showed that it is
an effective strategy for improving intake of nutrients such
as vitamin C, with the added benefit of reducing glycaemic
impact.
Lunch Seminar
–
Boehringer-Ingelheim
LN17-1
Translation into clinical practice: New findings in linagliptin
Per-Henrik GROOP
1
.
1
Helsinki University Central Hospital,
Finland
Cardiovascular (CV) and kidney disease remain significant
clinical challenges, and are key considerations in the man-
agement of patients with type 2 diabetes (T2D). In addition to
reducing the risk of developing complications, treatment
selection for patients with T2D is also influenced by individual
patient factors, including the risk of hypoglycaemia, the
presence of renal impairment, and requirements for dose
adjustment within a multi-drug regimen.
Professor Per-Henrik Groop from the University of Helsinki,
Finland, will begin his presentation by providing an overview
of the use of DPP-4 inhibitors for glucose control in patients
with renal dysfunction, including recent data for linagliptin in
this patient population. He will present data on the efficacy
and safety of linagliptin in patients with T2D and co-morbid
kidney disease, and will discuss how these data may translate
into clinical practice.
Professor Groop
’
s presentation will then describe the potential
effects of linagliptin beyond glucose control, discussing data
from the MARLINA-T2D
™
trial in patients with T2D at early
stages of diabetic kidney disease. In addition, he will discuss
the longer-termCARMELINA
®
trial, designed to investigate the
potential renoprotective effects of linagliptin treatment in
patients with more advanced diabetic kidney disease, and the
CAROLINA
®
trial, which will evaluate CV safety in patients
with T2D at elevated CV risk, including patients with chronic
kidney disease.
Speech Abstracts / Diabetes Research and Clinical Practice 120S1 (2016) S1
–
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