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Double diabetes does not have to mean double complications
Comment by Peter Lin,
MD, CCFP
T
ypically, we think of diabetes as either a
lack of insulin (type 1) or insulin resistance
(type 2), in which the insulin is not work-
ing well. We recognise that, along with insulin
resistance in type 2 diabetes, often comes a col-
lection of five metabolic derangements. These
include increased visceral fat as measured by
waist circumference, elevated blood pressure,
high triglycerides, low HDL, and high fasting
blood glucose. This collection of metabolic de-
rangements was labelled themetabolic syndrome
(MS). Patients with these features were found
to be at a much higher risk for cardiovascular
events, and these patients were easy to recognise
– they were the patients with the big bellies.
Now, typically we don’t think of patients
with type 1 diabetes as having big bellies and
so we don’t usually think in terms of metabolic
syndrome in patients with type 1 disease. But
why can’t a patient who is missing insulin also
have insulin resistance and all those metabolic
derangements as well?
This paper looked at that specific patient
group. Patients with type 1 diabetes and
metabolic syndrome. This combination was
given the nickname of double diabetes (DD).
In other words, these DD patients have both
insulin deficiency and insulin resistance.
The researchers found that, of 31,119 type
1 patients, 25.5% had MS. That is a much
higher proportion than one would expect. The
authors suggested that, maybe in the past,
patients had to adjust what they ate to their
insulin dose so they tended not to over-eat, and
hence obesity and MS was less likely. How-
ever, now with more flexible insulin dosing,
patients can eat what they want and they can
increase the insulin to match what they ate.
This would lead to more obesity and more MS
in the type 1 patients. The exact cause is not
yet clear but that is a sound hypothesis.
Unfortunately, what is clear is that patients
with DD have higher microvascular and mac-
rovascular disease complications.
MACROVASCULAR
MS
NO MS
Coronary heart disease
8.0%
3.0%
Stroke
3.6%
1.6%
Diabetic foot syndrome
5.5%
2.1%
MICROVASCULAR
Retinopathy
32.4%
21.7%
Nephropathy
28.3%
17.8%
The good news is that patients with DD who
had HbA1c <7% had fewer complications than
DD patients with higher HbA1c. So there is
hope that we can intervene to reduce their risk.
The key message from this study is that MS
is a set of toxic metabolic derangements that
can be found in patients with type 1 or type
2 diabetes. We must be on the lookout for it,
and, in those patients withMS, we must protect
them from both macro- and microvascular dis-
ease. We can do this by providing good glucose,
blood pressure, lipid, and weight control for all
of these patients in order to help reduce their
risk. So, double diabetes does not have to mean
double the complications.
Dr Lin is Director, Primary
Care Initiatives, Canadian
Heart Research Centre.
Dual therapy reduces body weight,
prediabetes, and systolic blood pressure
in obese nondiabetic individuals
Comment by Silvio Inzucchi,
MD
T
here is obviously a lot of in-
terest in the combined dose
of the two diabetes drug cat-
egories associated with weight loss,
the GLP-1 receptor agonists and
the SGLT2 inhibitors. In addition to
potential enhanced effects on BMI,
at least one member of each of these
classes has been associated with
improved cardiovascular outcomes
in high-risk patients, namely empa-
gliflozin and liraglutide. Notably, in
the most recent set of recommenda-
tions about glucose-lowering therapy
in type 2 diabetes, the American
Diabetes Association (ADA) and the
European Association for the Study
of Diabetes (EASD) do not endorse
this combination since, at the time
the guidelines were released (early
2015), there were no published stud-
ies of this specific combination. This
paper tests the drug combination in
a small cohort of obese but nondia-
betic individuals. The drugs appear
to work reasonably well together,
although I was a bit underwhelmed
by the effects on body weight.
We look forward to future pub-
lications of this and similar drug
combinations in patients with
type 2 diabetes. We would point
out, however, that current out-of-
pocket costs for this combination,
depending on dose, can be in excess
of US$1000 per month! This seems
extraordinary for a glucose-reducing
strategy, no matter how effective it
might be.
Dr Inzucchi is
Professor of Medicine
(Endocrinology); Clinical
Director, Section of
Endocrinology; Director,
Yale Diabetes Center;
Director, Endocrinology
and Metabolism Fellowship, Yale
School of Medicine, Connecticut.
In those patients with MS, we must
protect them from both macro- and
microvascular disease.
Prevalence and comorbidities of double diabetes
Diabetes Research and Clinical Practice
Take-home message
•
“This large study (N = 31,119) of individuals in Germany demonstrates that the presence of meta-
bolic syndrome among people with type 1 diabetes (25% prevalence) significantly contributes
to both microvascular and macrovascular complications, independent of glycemic control. This
study provides clinicians with an evidence base to target both obesity and glycemic control in
patients with type 1 diabetes.”
•
Further long-term studies are required to investigate the effects of insulin resistance on patients
with autoimmune diabetes, and any development of metabolic syndrome in patients should be
prevented.
Abstract
BACKGROUND
A growing number of people with type
1 diabetes (T1DM) are identified with features of met-
abolic syndrome (MS) known as “double diabetes”,
but epidemiologic data on the prevalence of MS
in T1DM and its comorbidities are still lacking. Aim
of this cross sectional study is to better estimate
the prevalence of MS in T1DM, and to assess its
association with comorbidities.
METHODS
Data of 31,119 persons with autoimmune
diabetes mellitus were analysed for signs of MS and
presence of late complications. Double diabetes
was defined as T1DM coexisting with MS (obesity,
hypertension, dyslipidemia). Multiple linear or logis-
tic regression analyses were performed to identify
associations between double diabetes and late
complications.
RESULTS
25.5% (n=7926) of persons with T1DM pre-
sented additionally the MS. Persons with double
diabetes showed significantly more macrovascular
comorbidities (coronary heart disease 8.0% versus
3.0% w/o MS, stroke 3.6% versus 1.6%, diabetic foot
syndrome 5.5% versus 2.1%). Also microvascular
diseases were increased in people with double
diabetes (retinopathy 32.4% versus 21.7%, nephrop-
athy 28.3% versus 17.8%). Both macrovascular and
microvascular comorbidities were increased inde-
pendent of glucose control, even if patients with
good metabolic control (HbA1c <7.0%, 53 mmol/mol)
showed significantly less macrovascular (coronary
heart disease 2.3% versus 1.8%, p<0.0001) and
microvascular problems (retinopathy 8.7% versus
6.6%, p<0.0001).
CONCLUSIONS
Double diabetes seems to be an
independent and important risk factor for persons
with T1DM in developing macrovascular and micro-
vascular comorbidities. Therefore, patients should
be identified and development of MS should be
avoided. Longterm studies are needed to observe
the effect of insulin resistance on patients with au-
toimmune diabetes.
Diabetes Res Clin Pract
2016;119:48-56, Merger
SR, Kerner W, Stadler M, et al.
Dapagliflozin QD and exenatide QWdual therapy:
a 24-week randomized, placebo-controlled, phase
2 study examining effects on bodyweight and
prediabetes in obese nondiabetic adults
Diabetes, Obesity & Metabolism
Take-home message
•
This study evaluated 43 adults over 24 weeks of treatment. In the dapa-
gliflozin/exenatide group compared with the placebo group, prediabetes
was reduced to 34.8% from 85% (P < 0.01), body weight decreased by
4.13 kg (P < 0.001), and systolic blood pressure (SBP) was also reduced (a
difference of 6.7 mm Hg). Anticipated adverse reactions to injection were
higher in the dapagliflozin group than the placebo group.
•
A reduction in body weight, prediabetes, and SBP in obese nondiabetic
adults resulted from dapagliflozin/exenatide dual therapy versus placebo,
with no adverse effects reported.
Abstract
AIMS
Dapagliflozin as well as exenatide reduce bodyweight in patients with
type 2 diabetes. We explored the effects of dual therapy with these agents on
bodyweight, body composition, glycemic parameters, and systolic blood pressure
(SBP) in obese nondiabetic adults.
MATERIALS AND METHODS
This single-center, double-blind trial randomized 50
obese nondiabetic adults (aged 18-70 years; body mass index 30-45kg/m2) to
oral dapagliflozin 10mg once daily plus subcutaneous long-acting exenatide
2mg once weekly or placebo. Magnetic resonance imaging (MRI) assessed
change in body composition. Participants were instructed to follow a balanced
diet and exercise moderately.
RESULTS
Of 25 dapagliflozin/exenatide- and 25 placebo-treated participants, 23
(92%) and 20 (80%) completed 24 weeks of treatment, respectively. At baseline,
mean age was 52 years, 61% were female, mean bodyweight was 104.6kg, and
73.5% had prediabetes (impaired fasting glucose or impaired glucose tolerance).
After 24 weeks: dapagliflozin/exenatide versus placebo difference in bodyweight
loss was –4.13kg (95% confidence interval: –6.44, –1.81; p<0.001), mostly attribut-
able to adipose tissue reduction without lean tissue change; 36.0% versus 4.2%
achieved ≥5% bodyweight loss, respectively; and prediabetes was less frequent
with active treatment (34.8% vs 85.0%; p<0.01). Dapagliflozin/exenatide versus
placebo difference in SBP reduction was -6.7 mmHg. As expected, nausea
and injection-site reactions were more frequent with dapagliflozin/exenatide
than with placebo. Only 2 and 3 participants, respectively, discontinued due to
adverse events.
CONCLUSIONS
Compared with placebo, dapagliflozin/exenatide dual therapy
reduced bodyweight, prediabetes, and SBP over 24 weeks and was well toler-
ated in obese nondiabetic adults.
Diabetes Obes Metab
2016 Aug 23;[Epub ahead of print], Lundkvist P, David
Sjöström C, Amini S, et al.
OBESITY
VOL. 1 • No. 3 • 2016
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