July 2014: Genetics

Hello and welcome to the July edition of Diabetes Directions. In this issue we are delighted to bring you part one of faculty member Professor Stephen Bain's articles on Genetic Studies in Diabetes in which he covers basic terminology, the reasons for searching genes and the potential benefits of genetic analyses. Case studies put the theory into a real-life setting as always, and this month the cases are contributed by Diabetes Specialist Nurse, Gaynor Harrison.

On a contrasting note we bring you another short video; Dr Martin Stevens considers Diabetic Neuropathy and how it can best be managed and as always our health news and Read all About it selections deliver pithy and relevant summaries.

Following last month's article on Diabetic Retinopathy we have put our subscriber’s queries to Dr Deborah Broadbent and will publish them shortly. If you have any queries on Genetics and Diabetes or any aspects of diabetes management please get in touch with the faculty by emailing: diabetesdirections@omniamed.co.uk

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This Edition's Poll Result

These are the results from this edition's poll question (this poll is now closed):

How soon can diabetic retinopathy develop for a juvenile patient with newly diagnosed type 1 diabetes?

(A) Straight away (upon onset)
(B) After minimum of 2 years
(C) After minimum of 3 years
(D) After minimum of 4 years
(E) After minimum of 5 years

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Genetics Studies in Diabetes - Part 1
Professor Steven Bain

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Maturity-Onset Diabetes of the Young (MODY), Sub-type: HNF1A
Gaynor Harrison

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Maturity-Onset Diabetes of the Young (MODY), Sub-type: Glucokinase
Gaynor Harrison

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Read All About It

Association between Intensification of Metformin Treatment with Insulin vs Sulfonylureas and Cardiovascular Events and All-Cause Mortality Among Patients With Diabetes
Roumie CL et al. JAMA. 2014;311(22):2288-2296. Doi:10.1001/jama.2014.4312

A retrospective study, which used a cohort of veterans who were initially treated with metformin between 2001 and 2008 (n=178,341) and then subsequently added either insulin (n=2948) or sulfonylurea (n=39,990), compared the risk of a composite outcome of acute myocardial infarction (AMI), stroke hospitalization, or all-cause death. Results demonstrated that among diabetic patients who were receiving metformin, the addition of insulin versus a sulphonylurea was linked to an increased risk of non-fatal cardiovascular outcomes and all-cause mortality. For the primary outcome, there were 172 versus 634 events for patients who added insulin versus sulfonylureas, respectively (adjusted hazard ratio (aHR), 1.30; 95% CI, 1.07-1.58; P=0.009). Results for AMI and stroke rates were statistically similar, reported as 41 versus 229 events, respectively (aHR, 0.88; 95% CI, 0.59-1.30; P=0.52). For all-cause death rates, there were 137 versus 444 events, respectively (aHR, 1.44; 95% CI, 1.15-1.79; P=0.001). However, it was noted that further investigation was required to fully understand the risks associated with insulin use in this patient group.

Read the article: http://jama.jamanetwork.com/article.aspx?articleid=1878717

Incidence of Pancreatitis and Pancreatic Cancer in a Randomized Controlled Multicenter Trial (SAVOR-TIMI 53) of the Dipeptidyl Peptidase-4 (DPP-4) Inhibitor Saxagliptin
Raz I et al. Diabetes Care. Doi: 10.2337/dc13-2546

Type 2 diabetic patients (n=16,492, aged ≥40 years old with established cardiovascular (CV) disease or CV risk factors, randomised to saxagliptin or placebo and followed for 2.1 years) were assessed to determine the incidence of pancreatitis and pancreatic cancer in the SAVOR-TIMI 53 study. In each treatment arm, it was confirmed that 26 events of pancreatitis was observed in 24 patients [0.29%] in the saxagliptin group, and 25 events in 21 patients [0.26%] in the placebo group (hazard ratio (HR) of 1.13, 95% CI, 0.63-2.06, P=0.77). Investigators reported no differences in time to event onset, concomitant risk factors for pancreatitis, investigator-reported causality from study medication or disease severity, and outcome between the treatment arms. Therefore, it was concluded that under the study (within 2.1 years of follow-up), the risk for pancreatitis in type 2 diabetic patients treated with saxagliptin was low and reportedly similar to placebo, with no sign of increased risk for pancreatic cancer.

Read the article: http://care.diabetesjournals.org/content/early/2014/06/05/dc13-2546.abstract

Retinal Vessel Calibers Predict Long-term Microvascular Complications in Type 1 Diabetes Mellitus
Broe R et al. Diabetes. Doi: 10.2337/db14-0227

In a bid to better understand the underlying pathology and effect diabetic neuropathy, nephropathy and proliferative retinopathy has on type 1 diabetic patients, preclinical biomarkers were examined as potential predictors of these complications in a Danish cohort with type 1 diabetes. The study utilised automated computer software to analyse vessel diameters, which demonstrated that both wider venular diameters and smaller arteriolar diameters were predictive of the 16-year development of neuropathy, nephropathy and proliferative retinopathy. Thus, it was concluded that early retinal vessel caliber changes could act as early markers of microvascular processes, precede the development of microvascular complications and may be used as a potential non-invasive predictive test to assess the future risk of diabetic neuropathy, nephropathy and retinopathy complications.

Read the article: http://diabetes.diabetesjournals.org/content/early/2014/06/09/db14-0227

Outpatient Glycemic Control with a Bionic Pancreas in Type 1 Diabetes
Russell SJ et al. NEJM. Doi: 10.1056/NEJMoa1314474

As part of two random-order, crossover studies, glycaemic control using a wearable, bihormonal, automated 'bionic' pancreas (bionic-pancreas period) was compared with glycaemic control with an insulin pump (control period), in order to assess the safety and effectiveness of automated glycaemic management. The studies included adults (n=20) and adolescents (n=50) with type 1 diabetes over a five day period. From the results, after 1 day of automatic adaptation by the bionic pancreas, the mean (±SD) glucose level on continuous monitoring was lower than the mean level during the control period (133±13 vs 159±30 mg per decilitre [7.4±0.7 vs 8.8±1.7 mmol per litre], P<0.001). It was concluded that when compared with an insulin pump, the automated, bihormonal bionic pancreas improved mean glycaemic levels, with less frequent hypoglycaemic episodes, in both adults and adolescents with type 1 diabetes mellitus.

Read the article: http://www.nejm.org/doi/full/10.1056/NEJMoa1314474

Differential reduction in corneal nerve fiber length in patients with type 1 or type 2 diabetes mellitus
Stem MS et al. Diabetes and Its Complications. Doi: 10.1016/j.jdiacomp.2014.06.007

In a cross-sectional study, diabetic patients without diabetic neuropathy (DN) (n=25), patients with mild (n=10) or severe DN (n=8), and participants without diabetes (n=9) were examined to determine the relationship between corneal nerve fibre length (CNFL) and DN status in patients with diabetes mellitus (DM). Using corneal confocal microscopy (CCM) of the sub-basal nerve plexus, analysis of the CCM images was utilised to quantify the average CNFL, and ANOVA was used to assess for CNFL differences. Results showed that all subjects without DN had type 1 diabetes and participants with DN had type 2 diabetes. It was also reported that participants with severe DN had significantly lower CNFL (12.5±6.1 mm/mm2) when compared to controls (20.7±2.2 mm/mm2, P=0.009). However, lower CNFL was also found in participants with type 1 diabetes who did not have DN (15.1±4.7 mm/mm2) compared to controls (P=0.033). Thus, it was concluded that CCM of the sub-basal nerve plexus could act as an indicator of early peripheral nerve degeneration in type 1 diabetes. It was acknowledged that type of diabetes, as well as the degree of neuropathy, may influence the extent of corneal nerve damage.

Read the article: http://www.jdcjournal.com/article/S1056-8727(14)00187-1/abstract

Genetic Variants in Transcription Factors Are Associated With the Pharmacokinetics and Pharmacodynamics of Metformin
Goswami S et al. Clinical Pharmacology & Therapeutics. Doi:10.1038/clpt.2014.109

As part of a pharmacodynamics study, genetic variants in transcription factors (TFs) were investigated as potential contributors to failure rate of metformin transporter pharmacokinetics and response. Participants contributed their genomic, pharmacokinetic and HbA1C data as part of the study. It was reported that variants in specificity protein 1 (SP1), a TF that modulates metformin transporter expression, were linked to changes in HbA1c treatment (P<0.01) and metformin secretory clearance (P<0.05). A confirmatory reduction of 24% was shown in homozygous carriers of the variant rs784888. Additionally, other TF genetic variants had demonstrated a significant association with HbA1c change.

Read the article: http://www.nature.com/clpt/journal/vaop/ncurrent/full/clpt2014109a.html

Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study
Mainous AG et al. BMJ Open. Doi: 10.1136/bmjopen-2014-005002

Data was collected by the Health Survey for England (HSE) in England in 2003, 2006, 2009 and 2011, in order to analysis potential trends surrounding the prevalence of prediabetes in individuals aged 16 years or older without previously diagnosed diabetes. Using participants' blood samples, individuals were classified as prediabetic if HbA1c levels were between 5.7% and 6.4% and not previously diagnosed with diabetes. It was shown that the prevalence of prediabetes had risen from 11.6% to 35.3% between 2003 and 2011. By 2011, a significant proportion of the population who were overweight (50.6%, body mass index (BMI)>25) and more than 40 years of age also had prediabetes. Interestingly, individuals with greater socioeconomic deprivation were more likely to have prediabetes in 2003 (P=0.0008) and 2006 (P=0.0246). However, this link was not deemed as significant in years 2009 (P=0.213) and 2011 (P=0.3153). The study confirmed that there has been a significant increase in the number of adults with prediabetes in England. The study also re-enforced the notion that the socioeconomically deprived are a considerable risk, and without a rigorous solution, the proportion of prediabetic individuals will only increase further.

Read the article: http://bmjopen.bmj.com/content/4/6/e005002


Diabetes gene increases risk tenfold

From research published in Nature, it has been shown that a variation in the TBC1D4 gene (in a population in Greenland, n=2575) increased the risk of developing type 2 diabetes by up to ten times. Danish researchers leading the study reported that the genetic mutation was observed in almost one in five Greenland participants (17% of population studied); however, it was not seen in other population groups (European, Chines, African-American), thus suggesting that type 2 diabetes is not solely caused by this gene. Nonetheless, the significance of these findings will help pave the way in preventing and treating type 2 diabetes.

Read the article: http://www.bbc.co.uk/news/health-27886184

Canola oil helps control blood glucose in type 2 diabetes patients

Giving canola oil to type 2 diabetes patients can help improve their blood cholesterol and blood glucose control by reducing glycaemic load, particularly with those at highest risk of diabetes complications, according to new research disclosed at the 74th American Diabetes Association in San Francisco, California. As part of the randomized trial, 141 participants with type 2 diabetes (already taking drugs to control their blood glucose) were given either a test or a control diet for a three month period. The test diet was low-GI and higher in fat, including bread made with canola oil. The control diet was healthy, low-fat and high in fibre. Results confirmed that that those who consumed the canola oil diet had improved blood glucose control.

Read the article: http://drugstorenews.com/article/canola-oil-helpful-blood-glucose-control-type-2-diabetics

Intensive, extended breastfeeding reduces type 2 diabetes risk after gestational diabetes

As part of a SWIFT (Study of Women, Infant Feeding and Type 2 diabetes after gestational diabetes mellitus pregnancy) study, researchers have shown that intense extended breastfeeding reduced a woman's risk for developing type 2 diabetes post pregnancy in which they had gestational diabetes. The observational study, which ran from 2008 to 2014, included a cohort of women (n=1010, aged between 20 and 45 years) with recent gestational diabetes to assess the effect of breastfeeding on type 2 diabetes development. It was demonstrated that women who exclusively breastfed at six to nine weeks postpartum showed a 61% risk reduction in their 2-year diabetes incidence (HR=0.39; 95% CI, 0.22-0.77). While those who breastfed at any frequency showed a nearly 40% reduction (mixed feeding HR=0.61; 95% CI, 0.34-1.08; mostly breastfeeding HR=0.66; 95% CI, 0.41-1.07). The conclusion was that lactation duration was associated with reduced risk of diabetes incidence in the 2-year period.

Read the article: http://www.healio.com/endocrinology/diabetes/news/online/%7Bc51d6699-c2e7-4fa5-bb26-a20f851848e9%7D/intensive-extended-breastfeeding-linked-to-reduced-risk-for-type-2-diabetes-after-gestational-diabetes

Adults with type 2 diabetes and improved physical fitness reduce risk of CKD

Findings from a new study presented at the joint International Society of Endocrinology and the Endocrine Society (ICE/ENDO) meeting showed that participants with type 2 diabetes who had improved their physical fitness reduced their risk of developing chronic kidney disease (CKD). Additionally, if they already had kidney damage, their kidney function was improved. Data analysis from the two-part study (with an average follow-up period of seven years) revealed that the combined death rate and CKD progression was much lower with an increased level of fitness. Compared with the least fit patients, highly fit patients showed a 68% lower combined CKD-death rate, and the moderately fit group showed a 51% lower rate of CKD progression and death. Interestingly, even the low-fit group had a 41% reduced rate when compared to the least fit group. Lead investigator Shruti Gandhi stated that 60 to 90 minutes of exercise weekly "is not a burdensome amount. Our study, while small, provides hope to patients with progressive kidney disease that there is something we can do to improve their kidney function and perhaps prevent or delay the need for dialysis."

Read the article: http://www.news-medical.net/news/20140624/Adults-with-Type-2-diabetes-who-improve-physical-fitness-lower-chances-of-getting-CKD.aspx