Research
Diabetes is a serious and growing concern worldwide. Millions of people are affected everyday by diabetes, with over 382 million people living with diabetes worldwide. Diabetes is already considered a global epidemic and is expected to keep increasing, with the International Diabetes Federation estimating numbers to rise to over 590 million by 2035. The only way the complex problems of diabetes will be resolved is through essential research to unlock the diabetes mystery.
The Diabetes Service is working hard to help uncover the answers to the complex problems of diabetes by pin pointing causes, understanding the genes behind diabetes, and reviewing clinical practise to improve clinical treatments. Due to the unique nature of the Diabetes Service, our research outcomes directly impact on the care of our patients and the wider community.
https://www.garvan.org.au/research/diabetes-metabolism/clinical-diabetes-appetite-metabolism
https://www.garvan.org.au/research/diabetes-metabolism/clinical-diabetes-appetite-metabolism/prader-willi-syndrome-and-genetic-forms-of-diabetes
2018
Title: Complex interplay among adiposity, insulin resistance and bone health.
Journal: Clin Obes
Authors: Ma C, Tonks KT, Centre JR, Samocha-Bonet D, Greenfield JR
Description: It is becoming increasingly recognized that diabetes is a
risk factor for fracture (broken bones). This article explores the
complex interaction between overweight, insulin resistance (a precursor
of diabetes), and worsening bone health. It summarises not only work
done at the Garvan Institute and St Vincent’s Hospital, but also what is
known worldwide on this topic up to this date.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/29334695
Title: High Risk Foot Service reduces number of Emergency Department presentations and length of stay
Journal: Diabetes & Metabolism
Authors: Lasschuit JWJ, Greenfield JR, Tonks KT
Description: Diabetes-related foot complications lead to significant burden for both individuals and the healthcare system. Development of High Risk Foot Services (HRFS) is a priority internationally, with the aim to provide essential interdisciplinary care to people with diabetes-related foot complications and improve clinical outcomes. However, dedicated funding is scare. The St Vincent's Hospital Sydney HRFS is the first in Australia to publish lower average cost per admission for ulceration and toe amputation in those attending the service compared to other admitted patients with diabetes. Attendees to the HRFS also spent less time in hospital when admitted for toe amputation compared to other patients with or without diabetes. Further, admissions via the Emergency Department were less likely, as our HRFS coordinates direct ward admission.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/30054153
2017
Title: Bone turnover is suppressed in insulin resistance, independent of adiposity.
Journal: J Clin Endocrinol Metab
Authors: Tonks KT, White CP, Center JR, Samocha-Bonet D, Greenfield JR.
Description: In this innovative article we look at the emerging
connection between bones and metabolism. Until recently it was thought
that although bone was metabolically active, it didn’t relate directly
to whole body metabolism. This research shows that there is a
relationship between weight and bone density (which was already known),
as well as insulin resistance and bone activity. To show this we
compared overweight insulin-sensitive and overweight insulin-resistant
people’s bone turnover markers. This is likely to be due to higher
insulin levels in more insulin-resistant people, causing suppression of
the bone turnover markers.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/28324004
Title: Euglycaemic diabetic ketoacidosis in patients using sodium-glucose co-transporter 2 inhibitors.
Journal: Intern Med J
Authors: Isaacs M, Tonks KT, Greenfield JR
Description: At St Vincent’s hospital we were the first in Australia to
report on this now well-recognised complication of these medications
(trade names: Forxiga, Jardiance, Xigduo and Jardiamet). Euglycaemic
diabetic ketoacidosis is a potentially life-threatening complication of
the use of these medications, particularly in people who are fasting for
surgery.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/28580740
Title: The value of the sulfonylurea gliclazide compared to newer oral antidiabetic agents.
Journal: Therapeutische Umschau
Authors: Viardot A
Description: Sulfonylureas (SU) are widely used drugs for the treatment
of patients with type 2 diabetes. They used to be, and still are in many
countries, the standard choice as a second-line agent after failure of
metformin monotherapy. Newer oral antidiabetic agents (OAD) are
increasingly used and tend to replace SU at a high cost to the
healthcare system, even though SU have been shown to be the most
cost-effective OAD. Also, over 60 years of clinical experience have well
demonstrated its efficacy, durability as well as the safety of SU.
Gliclazide is an SU of the newest generation and is the preferred choice
in many European countries due to distinct benefits. In contrast to
older SU, it has shown to protect the pancreatic beta-cell from
apoptosis, which is demonstrated by its durable effect in clinical
trials. Due to its distinct pharmacokinetic and specific binding to the
sulfonylurea receptor in pancreatic beta-cells, gliclazide is also
associated with the lowest risk for hypoglycemia compared to other SU.
Whilst the question of the cardiovascular safety of SU is still open,
gliclazide repeatedly showed the lowest cardiovascular risk in recent
observational studies and randomised controlled trials.
Link to publication: https://econtent.hogrefe.com/doi/pdf/10.1024/0040-5930/a000936
2016
Title: Trends in Metformin Utilisation and Dose Appropriateness in Australia.
Journal: Eur J Clin Pharmacol.
Authors: Moon J, Kumar S, Graham GG, Baysari MT, Williams KM, Chen W, Viardot A, Greenfield JR, Day RO.
Description: These researchers aimed to determine the trends in the
utilisation of metformin in Australia, determine the appropriateness of
metformin dosing in an Australian teaching hospital and gather the
opinions of prescribers on the relationship between metformin dose and
renal function. They showed that he use of metformin increased greatly
over the period of the study. Metformin is prescribed frequently for
patients with eGFR values below the minimal level approved in the
product label (60 mL/min). While prescribers expressed their
understanding of the need to reduce metformin doses in patients with
renal impairment, we found that metformin doses were higher than
appropriate in patients with impaired renal function. They conclude that
metformin may be used safely when renal function is poor provided
dosage is appropriately reduced.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=Trends+in+Metformin+Utilisation+and+Dose+Appropriateness+in+Aus
2015
Title: Long term glycaemic control (HbA1c), not admission glucose, predicts hospital re-admission in diabetic patients.
Journal: Australas Med Journal
Authors: Chai TY, Tonks KT, Campbell LV.
Description: Short term glucose control is measured by fingerprick and
blood glucose levels. Long term glucose control is measured by HbA1c. It
is known that people who have hyperglycaemia, or high blood glucose
levels, when they come to hospital have worse outcomes in terms of
infections and longer length of stay. In this paper we also describe
that high HbA1c, or chronically high glucose levels, more strongly
predict the need to keep going back to hospital. Whilst lots of effort
is put into achieving short term glucose control, we also need to
remember to organise follow-up so that people with high HbA1c will also
receive appropriate treatment.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/26213582
Title: Phenotypic Characterization of Insulin-Resistant and Insulin-Sensitive Obesity
Journal: Journal of Clinical Endocrinology and Metabolism
Authors: Chen DL, Liess C, Poljak A, Xu A, Zhang J, Thoma C, Trenell M,
Milner B, Jenkins AB, Chisholm DJ, Samocha-Bonet D, Greenfield JR
Description: Researchers at the Diabetes Service and the Garvan
Institute have published a report on the paradox of
metabolically-healthy obese (MHO) in the November issue of the Journal
of Clinical Endocrinology and Metabolism. Due to the variability in
defining and identifying MHO they investigated the underlying phenotypic
and metabolic factors protecting these individuals. Nondiabetic obese
individuals with insulin sensitivity at the muscle and/or liver provided
metabolic protection and included benefits such as lower blood pressure
and lower visceral and liver fat. By identifying these underlying
factors in obese individuals future treatments could be personalised to
the individual.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=26378474
Link to Garvan Institute press release: http://www.garvan.org.au/news-events/news/exploring-the-paradox-of-metabolically-healthy-obesity
Title: Healthcare professional requirements for the care of adult diabetes patients managed with insulin pumps in Australia.
Journal: Internal Medicine Journal
Authors: Xu S, Alexander K, Bryant W, Cohen N, Craig ME, Forbes M,
Fulcher G, Greenaway T, Harrison N, Holmes-Walker DJ, Howard G, Jackson
J, Jenkins A, Kamp M, Kaye J, Sinha A, Stranks S, O'Neal D, Colman P;
(The Australian National Adult Insulin Pump Therapy Working Group).
Description: St Vincent’s own Diabetes Clinical Nurse Consultant, Wendy
Byrant, co-authored this interesting paper, recently published in the
Internal Medicine Journal of the Royal Australasian College of
Physicians.
The study looked at Healthcare Professional time spent in supporting
patients managing insulin pumps. Twenty-four Australian adult diabetes
services experienced in insulin pump management took part in the study
and collected information on 2577 health care professional – patient
interactions.
The results showed that on average:
• Nurses followed by doctors then dietitians spend the most time
supporting patients on insulin pumps per week (5.4/1.0/0.4 hours).
• Almost half of these encounters were to start insulin pump therapy.
• Time from pre-pump to stabilisation on the pump took approximately 12
weeks and required 9.2-hours of nurse time, 2.4-hours of dietitian time
and 1.8-hours of doctor time.
The authors concluded that healthcare funding models require urgent
review in order to adequately support people with diabetes using, or
wanting to use, insulin pumps when managing their diabetes.
Link to publication: http://www.ncbi.nlm.nih.gov/pubmed/?term=25370368
Title: Topiramate Therapy: Night Eating Cure with Five Year Sustained Weight Loss in an Obese Patient with Type 2 Diabetes
Journal: Journal of Endocrinology, Diabetes & Obesity
Authors: Macdonald G, McMahon C, Tisch S, Campbell L
Description: The researchers describe a woman who had been suffering
from a severe case of night eating, had been fighting obesity for many
years and struggling to manage diabetes. Night eating is a condition
where people compulsively overeat after the evening meal and wake at
least once through the night to eat. This condition causes weight gain
and obesity, is exacerbated by stress and is associated with mental
illness like depression, all issues known to complicate diabetes
management. Topiramate treatment for essential tremor, a condition
unrelated to diabetes and eating challenges, has changed the patient’s
eating habits. Our patient achieved complete and sustained suppression
of night eating for five years. She has experienced minimal side effects
from this drug with dramatic weight loss, improvements in glycaemic
control and daily life.
Link to publication: https://www.jscimedcentral.com/Endocrinology/endocrinology-3-1067.pdf
Title: Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults
Journal: Gut
Authors: Chambers
ES*, Viardot A*, Psichas A*, Morrison DJ*, Kevin G. Murphy, Sagen E.K.
Zac-Varghese, Kenneth MacDougall, Tom Preston, Catriona Tedford, Graham
S. Finlayson, John E. Blundell, Jimmy D. Bell, E. Louise Thomas, Shahrul
Mt-Isa, Deborah Ashby, Glen R.Gibson, Sofia Kolida, Waljit S. Dhillo,
Stephen R. Bloom, Wayne Morley, Stuart Clegg, Gary Frost.
Description: The colonic microbiota ferment dietary fibres, producing short chain fatty
acids. Recent evidence suggests that the short chain fatty acid
propionate may play an important role in appetite regulation. In this
study, researchers developed a novel method to deliver propionate
specifically to the colon. A randomised, controlled cross-over study was
used to assess the effects of this inulin-propionate ester on energy
intake and gut hormones. The researchers demonstrated that ingestion of
10 g inulin-propionate ester daily over 24 weeks significantly increased
postprandial gut peptide levels, reduced energy intake and
significantly reduced weight gain, as well as liver fat content.These
data demonstrate for the first time that increasing colonic propionate
prevents weight gain in overweight adult humans.
Link to publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680171/
2014
Title: Comment on Brethauer et al. Bariatric surgery improves
the metabolic profile of morbidly obese patients with type 1 diabetes.
Journal: Diabetes Care
Authors: Tang A, Milner KL, Tonks K, Campbell LV, Greenfield JR.
Description: Bariatric surgery is used to treat obesity, and is known to
improve glucose levels in people with type 2 diabetes, presumably by
also treating insulin resistance. We describe several patients who have
type 1 diabetes, a condition marked by insulin deficiency rather than
insulin resistance, who have undergone bariatric surgery. We show that
for people with type 1 diabetes who undergo bariatric surgery also have
improvement in glucose control, as well as needing less insulin. This is
probably because they also have a degree of insulin resistance in
addition to their insulin deficiency.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/25342844
Title: Future management of human obesity: understanding the meaning of genetic susceptibility.
Journal: Advances in Genomics and Genetics
Authors: Jenkins AB, Campbell LV.
Description: The researchers discuss obesity and its causes, preventions
and treatments. The cause of obesity is complex and involves
gene-environment interactions. The researchers talk about the strong
genetic background to obesity, however after much research only few
genetic variants have been identified using high body mass index as the
usual phenotype. More informative phenotypes in genetic obesity studies
are limited and the researchers suggest possible analyses to derive such
phenotypes. They discuss the effects of obesogenic environments in
genetically predisposed individuals and how obesity levels may have
reached saturation in developed countries while still rising in
developing countries. The researchers question current obesity
preventions and treatments, showing most strategies have little effect
and may do more harm than good. They challenge current thinking that
obesity is a personal choice and call for an end to blaming the
individual.
Link to publication: https://www.dovepress.com/future-management-of-human-obesity-understanding-the-meaning-of-geneti-peer-reviewed-article-AGG
Title: Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults.
Journal: Gut
Authors: Chambers
ES*, Viardot A*, Psichas A*, Morrison DJ*, Kevin G. Murphy, Sagen E.K.
Zac-Varghese, Kenneth MacDougall, Tom Preston, Catriona Tedford, Graham
S. Finlayson, John E. Blundell, Jimmy D. Bell, E. Louise Thomas, Shahrul
Mt-Isa, Deborah Ashby, Glen R.Gibson, Sofia Kolida, Waljit S. Dhillo,
Stephen R. Bloom, Wayne Morley, Stuart Clegg, Gary Frost.
Description: The colonic microbiota ferment dietary fibres, producing short chain fatty
acids. Recent evidence suggests that the short chain fatty acid
propionate may play an important role in appetite regulation. In this
study, researchers developed a novel method to deliver propionate
specifically to the colon. A randomised, controlled cross-over study was
used to assess the effects of this inulin-propionate ester on energy
intake and gut hormones. The researchers demonstrated that ingestion of
10 g inulin-propionate ester daily over 24 weeks significantly increased
postprandial gut peptide levels, reduced energy intake and
significantly reduced weight gain, as well as liver fat content.These
data demonstrate for the first time that increasing colonic propionate
prevents weight gain in overweight adult humans.
Link to publication: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4680171/
2013
Title: Segregation of a latent high adiposity phenotype in families with a history of type 2 diabetes mellitus implicates rare obesity-susceptibility genetic variants with large effects in diabetes-related obesity.
Journal: PLOS ONE
Authors: Jenkins AB, Batterham M, Samocha-Bonet D, Tonks K, Greenfield JR, Campbell LV.
Description: In a voluntary overfeeding study researchers compared
healthy non-diabetic subjects who had a first degree family history of
type 2 diabetes (T2D) with subjects without such a history. They found
that subjects with a family history of T2D have genes that are involved
in weight gain and obesity that are rare and diverse. This research
provides evidence for a change to the approach to gene discovery in T2D
and obesity, with more emphasis on accurate phenotyping and family
studies.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=23950934
Link to Garvan Institute Press Release: https://www.garvan.org.au/news-events/news/a-complex-story-behind-genes-environment-diabetes-and-obesity.html
Title: Sugar-sweetened beverages, genetic risk, and obesity (Letter)
Journal: New England Journal of Medicine
Authors: Greenfield JR, Samaras K, Campbell LV.
Description: The researchers submitted a letter to the editor of the New
England Journal of Medicine in response to a study that reported on the
deleterious effects of sugar-sweetened drinks on body-mass index in
people with a predisposition to obesity. This letter highlighted the
genetic drive to consume these drinks, pointing out that it was not a
choice for individuals that have this predisposition. They also urged
public health policy makers to understand the science behind this
predisposition to obesity and protect individuals affected by these
genes.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=23323908
Link to Garvan Institute Press Release: https://www.garvan.org.au/news-events/news/the-genes-that-drive-soft-drink-consumption-and-weight-gain.html
Title: Putting PAID to diabetes-related distress: the potential
utility of the problem areas in diabetes (PAID) scale in patients with
diabetes.
Journal: Psychosomatics
Authors: Reddy J, Wilhelm K, Campbell L.
Description: The researchers studied distress and glycaemic control in
people with type 1 and type 2 diabetes. They used various
questionnaires, including PAID (a specific test for diabetes related
distress), and a measurement of average plasma glucose concentration
over time (HbA1c). The researchers found specific diabetes-related
distress was significantly related to impaired glycaemic control and
both current and past depression.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=23295006
Link to Garvan Institute Press Release: https://www.garvan.org.au/news-events/news/measuring-distress-in-people-with-types-1-and-2-diabetes.html
Title: Immune cell-mediated inflammation and the early improvements in glucose metabolism after gastric banding surgery.
Journal: Diabetologia
Authors: Samaras K, Viardot A, Botelho NK, Jenkins A, Lord RV.
Description: The researchers describe how rapid improvements in glucose metabolism
after gastric banding surgery are related to reductions in circulating
pro-inflammatory immune cells, specifically T lymphocytes, who are
involved in creating a pro-inflammatory environment in the setting of
obesity.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=Immune+cell-mediated+inflammation+and+the+early+improvements+in+glucose+metabolism+after+gastric+banding+surgery
2012
Title: Insulin sensitive obesity in humans - a ‘favourable fat’ phenotype? (Review)
Journal: Trends Endocrinol Metab
Authors: Samocha-Bonet D, Chisholm DJ, Tonks K, Campbell LV, Greenfield JR.
Description: Not all obese people are created equal – whilst the
majority are at risk of cardiovascular disease like heart attacks,
between 15% and 30% don’t seem to have that increased risk. These
“insulin-sensitive obese” people differ from their insulin-resistant
counterparts in terms of liver fat, inflammation and other factors that
are explored in this review article.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/22284531
Title: Recreational drug use in type 1 diabetes: an invisible accomplice to poor glycaemic control?
Journal: Internal Medicine Journal
Authors: Lee P, Greenfield JR, Gilbert K, Campbell LV.
Description: The researchers studied recreational drug use in people
with type 1 diabetes using an anonymous survey. They found
three-quarters of those that responded had used recreational drugs and
their use was associated with worse glycaemic control.
Link to publication: https://www.ncbi.nlm.nih.gov/pubmed/?term=22356493
Title: Association between serotonin transporter promoter polymorphisms and psychological distress in a diabetic population.
Journal: Psychiatry Research
Authors: Wilhelm K, Gillis I, Reddy J, Mitchell PB, Campbell L, Dobson-Stone C, Pierce KD, Schofield PR.
Description: The researchers studied the relationship between the
presence or absence of genes that regulate serotonin and depression and
anxiety in people with diabetes. They found that a specific genotype was
associated with significantly higher psychological distress within this
group. Therefore, the genetic makeup of diabetic individuals influences
their ability to cope with stress.
Link to publication: http://www.ncbi.nlm.nih.gov/pubmed/?term=22921508
Link to Garvan Institute Press Release: https://www.garvan.org.au/news-events/news/measuring-distress-in-people-with-types-1-and-2-diabetes.html