PRactice IMpact
D I A B E T E S
Vol 1 Issue 1 January 2010 © PRIMER
In this Issue
1. Is it time to bury the sulfonylureas?
2. Postpartum screening after a pregnancy with
GDM
3. Do statins cause diabetes?
4. Metformin What next: In cancer?
5. Primary prevention of cardiovascular disease:
ASPIR(IN)OUT?
6. Treating Mild Gestational Diabetes – More
heat and some light.
1.IS IT TIME TO BURY THE SULFONYLUREAS?
The Article: Tzoulak i I, Molokhia M, Curcin V, Little
MP, Millet CJ, Ng A, Hughes RI, Khunti K, W ilk ins
MR, Majeed A, Elliot P. Risk of cardiov asc ular
disease and all cause mortality among patients with
Type 2 diabetes prescribed oral antidiabetes drugs:
retrospective cohort study using UK general practice
res earch database. BMJ 2009; DOI: 10.1136/bmj.
b4731
What do we already know? What did we
learn?
Oral antidiabetic drugs are the mainstay of
treatment in Type 2 Diabetes mellitus. These
drugs belong to one of the following groups:
sulfonylureas,biguanides, thiazolidinediones
(TZD), alphaglucosi-dase inhibitors and the
recently introduced DPP 4 inhibitors. Due to the
difference in mechanism of action they can be
used in different combinations with an add-on
improvement in efficacy.
Tzoulaki and colleagues have done a
retrospective analysis of UK general practice
research database (1990-2005) involving oral
antidiabetic prescription in >90000 diabetics aged
35 to 90 yrs. Metformin was the most commonly
prescribed drug (74.5%) followed by second
generation sulfonylureas (63.5%). The primary
outcomes measured were incident myocardial
A professional service brought to you through an
unrestricted grant from Novartis.
From the Editors
We are delighted to present to you the first issue of
Practice Impact - Diabetes, a newsletter on the
clinical practice of diabetes specifically created for
busy physicians in the forefront of patient care. This
newsletter will reach your desk or Inbox every
quarter based on your preference.
How is Practice Impact different and how can it
help you? Practice impact has been conceived and
developed by practicing physicians who understand
how difficult it is to find those rare pearls in the
literature that actually translate into a change in
practice. We will sift through the over 1200 articles
that are published each quarter about diabetes, and
pick six that will be relevant to the practice of
diabetes in India. Once these six articles are chosen
we will write up a summary, the practice impact and
create two boxes; one that provides in a nutshell a
quick read and another that summarizes the techs
and the specs. Each write up is edited by two other
editors with a particular eye for evidence, and
relevance to practice before it reaches the print
shop.
The distribution of Practice Impact has been made
possible through an unrestricted education grant
from Novartis. The editors would like to however
emphasize that the newsletter is conceived and
developed by physicians and the sponsors will not
influence the choice of articles, content or writers.
The endeavor of Practice Impact-Diabetes is to
provide cutting edge information at your desk or
desktop without leaving it. The objective is to
provide you with clear recommendations with which
you can align your practice with evidence. To
continue to keep Practice Impact relevant to you, we
require your input. Write to us at
contactpracticeimpact@gmail.com. We hope
practice impact can help you make an impact on the
lives of your patients.

PRactice IMpact Bottom Line
Is it time to bury the sulfonylureas?
Q: Are antidiabetic drugs associated with an
independent increase in risk of CV disease?
A: Maybe; stronger evidence exists for
sulfonylureas as compared to metformin or TZDs.
Should I change my practice?
With the current level of evidence it is wise to start
treatment with life style changes and metformin (as
recommended by ADA/ EASD). The add-on drug
could be a TZD or sulfonylurea in that order of
preference. The DPP IV inhibitors stake their claim
into in this equation as a tier 2 recommendation.
infarction, congestive heart failure and all cause
mortality. They conducted multivariate analysis of
each drug’s risk for the different end points using
three separate models that adjusted for
increasing number of variables. The first model
controlled for sex and diabetes duration, the
second added specific coexisting cardiovascular
disorders and drug therapies as further
covariates and the third (fully adjusted) added a
list of standard cardiovascular risk markers such
as lipids and blood pressure. Patients treated
with sulfonylureas as a group [when compared to
metformin], had more heart failure and increased
all cause mortality. As more covariates were
added, the association between sulfonylureas
and risk of MI became weaker. The increased all
cause mortality however remained significant
Techs and Specs
Is it time to bury the sulfonylureas?
Type of study: Observational; Retrospective
analysis
Level of Evidence: Level 2b†
Conflict of interests: Disclosed
Web location: http://www.
b mj.com/cgi/content/ab stract/339/dec03_1/b 4731
Access restrictions: Full text free
† From Phillips B, Ball Chriss, Sackett D, Badenoch D -
Oxford Centre for EvidenceBased Medicine Levels of
evidence 2001.http://www.cebm.net
(hazard ratio (HR)1.37 – 1.61) in the fully
adjusted model. Pioglitazone treated patients had
a better survival rate (31 - 39% lower risk) but the
benefit of pioglitazone over rosiglitazone was lost
GLOSSARY *
* Legend for initials is found in the Editorial Board Box
* The Initials in Bold italic indicate the author. The editors are indicated in Parenthesis.
once the data was analyzed in a fully adjusted
statistical model. The analysis found no
increased risk of myocardial infarction in patients
treated with TZDs including rosiglitazone.
The authors concluded that when compared with
metformin, sulfonylureas have a worse mortality
profile. Among the TZDs, pioglita-zone was
superior to rosiglitazone.
What is the practice impact?
The results of this observational study should be taken with
caution. The association between different drugs and CV
risk became increasingly weaker as more variables were
added. These studies however are important. They lend
more credibility to the safety concers raised about SUs. It
is difficult to draw definitive conclusions at present as
there are many confounding factors like existing risk for
heart disease, BMI, blood pressure etc. While it may be
premature to bury sulfonylureas, it looks like that the nails
in the coffin are being placed one study at a time. - MDC
(SRA, RTR)*
2.POSTPARTUM SCREENING AFTER A PREGNANCY
WITH GDM – AN OPPORTUNITY THAT KNOCKS
The article: Kwong S, Mitchell RS, Senior PA, Chik
CL. Postpartum diabetes screening: adherenc e rate
and the perform ance of fasting plasma gluc os e versus
oral glucos e tolerance test . Diabetes Care. 2009
Dec ;32(12):2242- 4
What do we already know? What did we
learn?
There is a significant prevalence of abnormal
glucose tolerance in the post partum period
between six and twelve months. Many patients
with gestational diabetes (GDM) will be
diagnosed as having diabetes impaired fasting
glucose (IFG), or impaired glucose tolerance
(IGT) at mid and long-term follow-up. The
prevalence of isolated IFG is 3 – 6%, that of IGT
is 7–29%, and that of diabetes is 5–14%, 4–20
weeks after pregnancy in women who were
diagnosed with GDM and received treatment
during gestation. A large proportion of these
women (11 – 21% in Asians) analyzed in various
studies develop diabetes within a decade if found
to have abnormal testing in the postpartum

PRactice IMpact Bottom Line
Postpartum screening after a pregnancy with
GDM – an opportunity that knocks
Q: What is the adherence to postpartum testing
A: Poor
Q: What test should be used in postpartum
screening?
A: 75 gram OGT
Should I Change My Practice?
Greater efforts should be made to educate patients to
screen for diabetes between 6 and 12 weeks post
partum. Postal /telephonic or SMS reminders after
delivery to obtain 75gm OGTT will significantly
increase the chances of detecting glucose intolerance
during the post partum period. The OGT should be
test of choice in this setting.
period. Importantly six randomized controlled
trials (RCTs) have shown that intervention
(lifestyle and medications) may be successful in
preventing or delaying diabetes in these The
purpose of delayed postpartum glucose testing is
to identify any type of glucose abnormality
present: IFG, IGT and diabetes. Both isolated
IFG and isolated IGT predict (to different
degrees) later risks of type 2 diabetes and CVD.
Combined IFG-IGT generally has the greatest
predictive power.
While the implications are clear, the translation to
practice is a challenge. In this article published
from a community hospital in Canada, women
with GDM between 35 and 40 weeks of gestation
were provided requisitions for postpartum testing.
They also received a telephone reminder if
testing was not completed. Only 48.2% of the
909 women completed testing, of which 21 only
completed a FPG. Higher parity and non use of
insulin contributed to the higher rate of non
adherence. This is consistent with previous
studies that show poor adherence to published
guidelines in this regard. Interestingly, this is in
sharp contrast to the very high levels of
acceptance to intervention and follow up during
pregnancy itself.
Techs and Specs
Postpartum screening after a pregnancy with GDM
– an opportunity that knocks
Type of Study: Retrospective Cohort
Level of Evidence : III
Conflicts of Interest: None
Web location of article:
http://care.diabetesjournals.org/content/32/12/2242.full
Access restrictions: Free Full Text
A total of 14 women who had postpartum testing
in this study were diagnosed with type 2 diabetes;
while 15 had IFG, 57 had IGT, 3 had both. The
FPG and OGTT were abnormal in 25 (5.7%) and
89 (21.3%) women, respectively, whereas only 5
women had both abnormal FPG and 2-h PG
values. Interestingly, if only an FPG was
performed, 72% of women with postpartum
hyperglyce-mia would have been missed. This is
not in variance with other published data.
What is the practice Impact?
The article is a gentle reminder for us to not miss a window
of opportunity to screen women for glucose abnormalities
postpartum. It is possible that many of these women are
falsely reassured that the diabetes will disappear, when
there is sufficient data that the contrary is true. Glucose
abnormalities persist in up to 34.3% of patients following
pregnancy. The OGT is an important tool in detecting,
delaying and preventing diabetes in these women.
Physicians must use the relatively compliant period of
pregnancy to educate women on the postpartum
consequences of GDM and the need for identification and
testing. Communication with obstetricians to use the first
postpartum visit to reinforce testing for glucose
abnormalities may also be a key step - KGS (KMP)
References:
1) Dietz PM, Vesco KK, Callaghan WM, Bachman DJ, Bruce
FC, Berg CJ, England LJ, Hornbrook MC. Postpartum screening
for diabetes after a gestational diabetes mellitus-affected
pregnancy.,Obstet Gynecol. 2008;112:868-74.
3. DO STATINS CAUSE DIABETES?
The article - Rajpathak SN, Kumbhani DJ, Crandall J,
Barzilai N, Alderm an M, Ridk er PM. Statin therapy
and risk of dev eloping type 2 diabetes: a meta-
analys is . Diabetes Care. 2009 Oct;32:1924- 9 .
What do we already know? What did we
learn?
While the role of statins in the prevention of the
cardiovascular complications of diabetes is
certain, there is a nagging doubt whether statins
may actually cause diabetes. Several studies
including the recently published JUPITER trial
showed a marginal increase in the diagnosis of
diabetes in statin treated patients.
Rajpathak and colleagues reviewed 6
randomized clinical trials. Three studies
(WOSCOPS, the Anglo-Scandinavian Cardiac
Outcomes Trial [ASCOT], and JUPITER) were
primary cardiovascular prevention trials, whereas
 PRactice IMpact Bottom Line
Do statins cause diabetes?
Q: Do statins increase the risk of diabetes?
A: Maybe, we dont know yet
Should I Change my practice:
No. Statins remain the sheet anchor in the
management of dyslipidemia. The clinical concerns
about causation will need to be evaluated in future
studies.
three , were secondary prevention trials (the
Heart Protection Study [HPS], the Long-Term
Intervention with Prava-statin in Ischemic
Disease [LIPID] Study, and the Controlled
Rosuvastatin Multinational Study in Heart Failure
[CORONA]. Individually, WOSCOPS showed a
protective effect for statins against the
development of diabetes; the JUPITER trial
showed a small but significant risk for diabetes. It
must be noted that the WOSCOPS trial required,
in addition to a fasting glucose of greater than
126, an increase in the blood glucose of greater
than 36 mg/dL from baseline to qualify for a
diagnosis of diabetes.
When the WOSCOPS study was excluded, a
small but significant increase in the risk of
diabetes was noted.(1.13 (95% CI 1.03–1.24;
P = 0.007). When WOSCOPS was included, this
effect was no longer seen (1.06 (95% CI 0.93–
1.23; P = 0.38).
Techs and Specs
Do statins cause diabetes?
Type of Study: Metaanalysis of RCTs
Level of Evidence : I
Conflicts of Interest: Possible, Disclosed
Web location of article:
http://care.diabetesjournals .org/content/32/10/1924
Access restrictions: Free Full text
What explains the differences? First, this could
be a function the class of statins used.
Atorvastatin has been shown to decrease
glucose uptake in adipose cell lines, increase
A1C in hypercholesterolemic patients, and
decrease beta cell function. Simvastatin has been
shown to decrease insulin sensitivity, adiponectin
PRactice IMpact Editorial Board
Dr. KM Prasanna Kumar (KMP), Bengaluru
Dr. Krishna G Seshadri (KGS), Chennai
Dr. Aravind R Sosale (SAR), Bengaluru
levels and beta cell function. None of these
effects have been demonstrated with Pravastatin.
Second, the results may reflect the differences in
the population studied. For instance, there were
no women included in the WOSCOPS study
while upto 38% of patients enrolled in the
JUPITER trial were women.
What is the practice Impact?
The water is too muddy to make a recommendation to
change current practice. The results are only hypothesis
generating because they rely on data published previously
and thus are inherently observational. The development of
diabetes is of clinical concern because of the risk of its
associated complications. Because cardiovascular disease
accounts for almost two-thirds of deaths in people with
diabetes, the protective effect of statins on this major
complication may suffice to support their use despite a
potential risk of new-onset diabetes. There is also evidence
to suggest that statins may also improve microvascular
outcomes. The last word on this issue is yet to be written.
Watch this space. KGS (SRA, MC)*
References
1) Takaguri A, Satoh K, Itagaki M, Tokumitsu Y, Effects of
atorvastatin and pravastatin on signal transduction related to
glucose uptake in 3T3L1 adipocytes. J Pharmacol Sci. 2008
May;107(1):80-9.
2) Koh KK, Quon MJ, Han SH, Lee Y, Differential metabolic
effects of pravastatin and simvastatin in hypercholesterolemic
patients. Atherosclerosis. 2009: 483-90.
4. METFORMIN WHAT NEXT: IN CANCER?
The article: Gijs W . Landm an, Nanne Kleefstra,
Kornelis J.J. van Hateren, Klaas H. Groenier, R.O.B.
Gans, and H.J.G. Bilo Diabetes Care , Nov 2009;
10.2337/dc09- 1380. Metformin ass ociated with lower
c anc er mortality in type 2 diabetes (ZODIAC-16).
What do we already know? What did we learn?
The biguanides particularly metformin were
outcasts for over a decade; they returned and
rose to become favorite drugs of not only
endocrinologists and physicians but also of
gynecologists and infertility specialists. They now
appear to have taken on a new role as of
Dr. GR Sridhar (GRS), Visakhapatnam
Dr. Manoj D Chada (MDC), Mumbai
Dr. Subhankar Chowdury (SC), Kolkatta
Dr. Ambarish Mittal (AM), New Delhi
Dr. Radha T Reddy (RTR), Claremont, USA

PRactice IMpact Bottom Line
Metformin What next: In cancer?
Q: Is metformin use associaed with lower risk of
dying from cancer?
A: Yes
Should I change my practice?
Consider the additional benefit of starting metformin
early. Metformin is the first drug that should be
prescribed in diabetes for reasons other than its
antineoplastic activity Don’t lose track of glycemic
control though. Evidence is far more robust for good
glycemic control than it is for a protective action of
metformin against cancer.
antineoplastic agencies, attracting the attention of
oncologists.
Individuals with diabetes are not only prone to a
variety of neoplasia including those of the liver,
pancreas, endometrium, breast and colon, but
also respond poorly to therapy Commonly used
antidiabetic drugs such as sulfonylureas and
insulin lead to more deaths due to cancer.
Metformin (MF) appears to behave differently.
Earlier studies have suggested that its use may
lead to lower risk of cancer compared to other
antidiabetic drugs.
The current study from the ZODIAC
(Netherlands) group assessed the association
between use of MF and death due to cancer. The
Cox proportional hazard model was used, taking
confounders into account. In a median follow-up
of 9.6 years, there were 570 deaths among the
1353 strong cohort; 122 deaths were due to
malignancies. Patients taking MF had a lower
adjusted hazard ratio due to cancer death (0,43;
95% confidence interval 0.23-0.86). In addition
the hazard ratio was 0, 58 (95% CI 0.36-0.94) for
every increase of 1 gm dose. This prospective
study showed that use of metformin at baseline in
patients with diabetes was associated with a
lower rate of cancer related mortality; i.e., the
death rate in this subgroup of patients with
diabetes was not higher than that found in the
general population.
This study has strengths, confirming a series of
earlier reports: the ZODIAC group had a
prospective design; more potential confounders
were adjusted for; in addition the mortality was
compared to the general population cancer
mortality in the Netherlands. There are
limitations to the general conclusion though; the
type of cancer was not studied in relation either to
onset or type of antidiabetic treatment. Data were
obtained only at the time of starting metformin.
How does metform do all of this? Metformin
activates AMP kinase, a sensor that identifes
balance of cellular ATP and cAMP. AMP kinase
is postulated to have a role in tumour
suppression. The drug also has direct in vitro
inhibitory action on the proliferation of cancer
cells, though at much higher levels than seen
with doses used in the treatment of diabetes. It is
unclear whether the drug is actually protective,
blocks a potential mitogenic action of insulin, or,
is merely less often used in patients in this
population. Nevertheless, there is evidence that
metformin actually enhances the efficacy of
chemotherapy for established tumours. Ongoing
clinical trials have been started using metformin
in breast cancer treatment and prevention.
It is possible that the still-discarded biguanides
such as phenformin and buformin will have new
avatar, as anti-cancer agents. While the saying
Techs and Specs
Metformin What next: In cancer?
Type of Study: Prospective, observational cohort
study
Level of evidence: 1b
Conflict of interest: None declared
Web location of article:
http://care.diabetesjournals.org/content/early/2009/
11/12/dc09-1380.full.pdf+html
Access restrictions: Freely accessible in India
goes that there are no permanent friends or
enemies in politics, this perhaps holds truer in
pharmacotherapy.
What is the practice impact?
Metformin seems to have a role that extends beyond
lowering plasma glucose and body weight. It appears to
prevent cancers that are often more common and more
aggressive in individuals with diabetes. Should we tell all
our patients irrespective of their glycemic status to start
popping a metformin? Probably not. Clearly we have found
one more reason to start all our diabetics early on this
wonder drug (thats what the ADA and other pundits tell us
to do anyways for other reasons) and keep them on it as
long as possible. - GRS (KS)*.
References:
1) Chong CR, Chabner BA, Mysterious Metformin. The
Oncologist Express, published on December 10, 2009
2) Duncan BB, Schmidt MI, Metformin, cancer, alphabet soup and
the role of epidemiology in etiologic research. Diab Care 2009,
32:1748[2009].

5. PRIMARY PREVENTION OF CARDIO-VASCULAR
DISEASE: ASPIR(IN)OUT?
The article: Calvin AD, Aggarwal NR, Murad MH, Shi
Q, Elamin MB, Geske JB, et al. Aspirin for the prim ary
prevention of cardiovascular events: a sys tem atic
rev iew and meta-analysis comparing patients with and
without diabetes. Diabetes Care . 2009 Dec;32:2300-
6.
What do we already know? What did we
learn?
Almost all of the major society guidelines
recommend that low-dose aspirin therapy to be
used as primary prevention strategy in patients
with diabetes especially those at increased
cardiovascular risk. This group includes those
who are over 40 years of age, or those with
additional risk factors. These guidelines were
based on evidence extra-polated from trials of
high-risk patients. Aspirin use is not without its
safety concerns. There is a significant increase in
PRactice IMpact Bottom Line
Primary prevention of cardiovascular disease:
ASPIR(IN) OUT?
Q: Is Aspirin useful in Primary prevention of
cardiovascular events in diabetes
A : Probably not
Should I Change My Practice:
A: YES. Aspirin should continue to be used for
secondary prevention. In primary prevention, aspirin
must be used in adults with diabetes and no previous
history of vascular disease who are at increased CVD
risk (10-year risk of CVD events >10%) and who are
not at increased risk for bleeding. Aspirin should not
be recommended for those at low CVD risk (women
under age 60 years and men under age 50 years) with
no major CVD risk factors. Clinical judgement must
guide use in those with intermediate risk. A low dose
75 – 162 mg/ day appears to be a reasonable dose to
use in those in whom the drug is indicated until further
evidence is available.
the risk of gastrointestinal bleeding. Despite this,
aspirin for many years has been the holy grail of
cardiovascular (CV) risk reduction in diabetes.
Since patients with diabetes have a high
incidence of cardiovascular events, it was
presupposed that aspirin will also be effective as
primary prevention in patients with diabetes.
Cracks, however started to appear. Questions
about resistance to or ineffectiveness of aspirin
were increasingly raised in the literature. Two
recent randomized controlled trials of aspirin
specifically in patients with diabetes failed to
show a significant reduction in CV end points,
raising questions about the efficacy of aspirin for
primary prevention in people with diabetes. The
United States Prevention Services Task Force
(USPSTF) revised its evidence level and
recommendations on aspirin use; specifically it
encouraged aspirin use only in men between 45–
79 years of age and women 55–79 years of age,
irrespective of diabetes.
Techs and Specs
Primary prevention of cardiovascular disease:
ASPIR(IN) OUT?
Type of Study: Meta analysis of 9 RCT’s.
Level of Evidence : .Level 1
Conflicts of Interest: No potential conflict of Interest
reported
Web location of article:
http://care.diabetesjournals.org/content/32/12/2300.full
Access restrictions: Free full text
It is in this context that this metaanalysis
becomes relevant. The authors reviewed the
literature for trials comparing aspirin use in
patients with and without diabetes and no known
diagnosis of cardiovascular disease, ultimately
identifying nine eligible trials. A 95% confidence
interval (CI) that crosses 1.00 indicates that the
effect of aspirin does not differ between patients
with and without diabetes. The ratios of RRs
comparing the benefit of aspirin among patients
with diabetes compared with patients without
diabetes for mortality, myocardial infarction, and
ischemic stroke were 1.12 (95% CI 0.92–1.35),
1.19 (0.82–1.17), and 0.70 (0.25–1.97),
respectively. In spite of some methodologic
limitations, the meta analysis clearly identified
that there was no difference in the composite end
points in both diabetic & non diabetic groups.
Relative risk reduction for MI was statistically non
significant in the diabetic population. The analysis
also suggested that the relative benefit of Aspirin
is similar in patients with & without diabetes.
What is the practice Impact?
Since the publication of this article and before this
newsletter went into press the American Diabetes
Association ADA has revised its recommendations for the
use of aspirin in diabetes. Aspirin use for secondary
prevention is based on strong evidence base and continues
to be recommended. Until further evidence is available,
low-dose (75–162 mg/day) aspirin use for primary
prevention is reasonable for adults with diabetes and no
previous history of vascular disease who are at increased
CVD risk (10-year risk of CVD events >10%) and who are
not at increased risk for bleeding. This generally includes
most men over age 50 years and women over age 60 years
who also have one or more of the following major risk
factors: smoking, hypertension, dyslipidemia, family history
of premature CVD, and albuminuria. Aspirin should not be
recommended for those at low CVD risk (women under age
60 years and men under age 50 years with no major CVD
risk factors; 10-year CVD risk <5%), as the low benefit is
offset by the incidence of significant bleeding. Clinical
judgment should be used for those at intermediate risk
(younger patients with one or more risk factors or older
patients with no risk factors; those with 10-year CVD risk
5–10%) . This article highlights the importance of using
hard evidence as the basis of clinical care; clearly in
science no grail is too holy to question. SRA (RTR, KMP,
KGS)*
References:
1) Aspirin for the prevention of Cardiovascular Disease, Topic
page, March 2009.
2) US Preventive Services Task Force: Aspirin for the
prevention of cardiovascular disease: U.S. Preventive Services
Task Force recommendation statement. Ann Intern Med 2009;
150: 396– 404
3) Summary of Revisions for the 2010 Clinical Practice
Recommendations Diabetes Care 2010 33:S3;
6.TREATING MILD GESTATIONAL DIABETES –
MORE HEAT AND SOME LIGHT.
The article: Landon, MB. Spong CY, Thorn E,
Carpenter MW , et. al. A Mulcenter randomized trial of
treatment for Mild Gestational Diabetes. N Engl J
Med 2009. 361: 1339
What do we already know? What did we
learn?
Gestational Diabetes Mellitus (GDM) is
controversial in definition diagnosis treatment and
outcome. The recent hyperglycemia and
pregnancy outcomes (HAPO) trial showed a
strong and continuous correlation between
maternal glucose concentrations and markers for
perinatal complications. It is clear that very high
fasting glucose are associated with fetal
macrosomia and perinatal complications, the jury
is is still out on the association between milder
forms of GDM and outcomes. Langdon et al
screened women between 24-30 weeks of
gestation with 50 gram of glucose and chose
patients with values between 140 and 200(n =
10989) and performed a 100 g 3 h OGT. Women
PRactice IMpact Bottom Line
Treating Mild Gestational Diabetes – More heat
and some light
Q: Does control of mild gestational diabetes with
diet and or insulin reduce perinatal death or severe
neonatal outcomes?
A: No. However several secondary outcomes
including macrosomia, C section rates, gestational
hypertension however show improvement.
Should I Change My Practice?
Yes. Mild gestational diabetes must be treated with
lifestyle changes and or insulin. Efforts in limiting
excessive weight gain in obese women during
pregnancy may be beneficial.
with fasting glucoses > 95 were excluded. The
rest were randomized to either intensive care with
nutritional counseling and if needed insulin (n =
485) or to usual prenatal care (n = 473).
There were no differences between the two
groups in the composite perinatal primary
outcomes – still birth, perinatal death, neonatal
complications (RR 0.87 97% CI 0.72 to 1.07; p =
0.14). There were no fetal deaths in either group.
The mean birth weight, the neonatal fat mass, the
frequency of large for gestational age infants and
infants greater than 4000 g were significantly
lesser in the treatment group. In addition the
number of C Sections were also lower in the
treatment group (27 vs 34%). The treatment
group also had a lower incidence of shoulder
dystocia, preeclampsia and gestational
hypertension (9 vs 14%).
What is the practice Impact?
The study shows a firm but modest benefit of treating mild
GDM. This is consistent with other studies including the
(Australian Carbohydrate Intolerance Study in Pregnant
Women) ACHOIS study. Landon et al. did not show a
beneficial effect of glycemic control in lowering perinatal
mortality and severe neonatal complications. They however
Techs and Specs
Treating Mild Gestational Diabetes – More heat
and some light.
Type of Study: Prospective randomized multi-centric
trial
Level of Evidence : 1b
Conflicts of Interest: None disclosed
Web location of article:
http://content.nejm.org/cgi/content/short/361/14/1339
Access restrictions: Abstract free. Full text with paid
subscription
showed that such treatment lowers risk for several
secondary outcomes including shoulder dystortia and
gestational hypertension. It is interesting to note that many
of these secondary out comes are related to maternal
weight. In this context the results of the Landon trial may
extend beyond GDM. It must be remembered that
disproportionately more women with obesity deliver babies
with macrosomia than women with gestational diabetes. It
is not clear from clinical trials if maternal obesity, level of
glycemia, or treatment modalities are independently or
cumulatively responsible for fetal growth abnoramlities. In
the current study, weight gain in the treatment group was
significantly less than in the control group, and may
partially explain some of the benefits seen in terms of
secondary outcomes, such as macrosomia. From a practice
perspective it may be wise to limit excessive weight gain in
overweight and obese women and there is evidence to
support such an recommendation. The results of this study
add to ongoing efforts to develop an international
Printed by Chameleon Inc. and published by PRIMER on behalf of KM Prasannakumar, Aravind Sosale and Krishna Seshadri printed at 1/67, 1st
Floor, Raja Industrial Estate, P.K. Road, Mulund (West),Mumbai - 400 080 and published at Bengaluru;and Editor KM Prasanna Kumar
consensus for the diagnosis and treatment of carbohydrate
tolerance in pregnancy. While some nagging questions
remain, prudence dictates that mild Gestational Diabetes is
best offered therapy with lifestyle and if needed insulin.
KGS (GRS, RTR, SRA)*
References:
1) The HAPO study cooperative research group. Hyperglycemia
and Adverse Pregnancy Outcomes. N Engl J Med 2008. 358:
1991 – 2002
2) Sacks DA, Gestational Diabetes - Whom do we treat?. N Engl
J Med 2009. 361:1396-98.
3) Dodd JM, Crowther CA , Robinson JS. Dietary and lifestyle
interventions to limit weight gain during pregnancy for obese or
overweight women: a systematic review. Acta Obstet Gynecol
Scand 2008; 87:702-6.