Diabetes Service research


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: 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


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


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: http://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: http://www.jscimedcentral.com/Endocrinology/endocrinology-3-1067.pdf


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: http://www.dovepress.com/future-management-of-human-obesity-understanding-the-meaning-of-geneti-peer-reviewed-article-AGG


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: http://www.ncbi.nlm.nih.gov/pubmed/?term=23950934
Link to Garvan Institute Press Release: http://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: http://www.ncbi.nlm.nih.gov/pubmed/?term=23323908
Link to Garvan Institute Press Release: http://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: http://www.ncbi.nlm.nih.gov/pubmed/?term=23295006
Link to Garvan Institute Press Release: http://www.garvan.org.au/news-events/news/measuring-distress-in-people-with-types-1-and-2-diabetes.html


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: http://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: http://www.garvan.org.au/news-events/news/measuring-distress-in-people-with-types-1-and-2-diabetes.html