SITA (vs. SU) + MET users had significantly higher mean PDC, adherence, and persistence. These trends were robust to model alterations and were more marked when accommodating OPEs (Journal of Diabetes)
Archives for August 2016
Our findings demonstrate that H. pylori eradication improves glucose homeostasis in patients with type 2 diabetes through a decrease in pro-inflammatory factors (Nutrition, Metabolism & Cardiovascular Diseases)
Overnight closed-loop therapy resulted in better glucose control than sensor-augmented pump therapy in pregnant women with type 1 diabetes. Women receiving day-and-night closed-loop therapy maintained glycemic control during a high proportion of the time in a period that encompassed antenatal hospital admission, labor, and delivery (NEJM)
Given the epidemic of obesity, it is very easy to label every new patient presenting with raised blood glucose as having Type 2 diabetes (T2D). However, even NICE are recognising that other types of diabetes can occur atypically, for example Type 1 diabetes in the middle aged. On top of this, clinicians should be increasingly aware of the possibility that the kneejerk diagnosis of T2DM may be wrong. This is increasingly important given the increasing prevalence in younger patients The presence of a strong family history may indicate a specific subtype of diabetes – MODY (Maturity onset diabetes of the young). Also referred to as monogenic diabetes, the term refers to any of several hereditary forms of diabetes caused by mutations in an autosomal dominant gene. It affects 1-2% of all patients with diabetes and classically presents in patients aged less than 25 years, in families with a multigenerational history of relatively early onset diabetes. Caused by a change in a single gene, 6 genetic subtypes account for 87% cases of MODY in the UK. Diagnosis of a MODY family is of benefit as the natural history of each sub type can determine the long term medication and screening required. Furthermore, family members can be screened in order to predict their longer term risk. The commonest sub type (HNF1A) is responsible for 70% of MODY cases. A gene mutation results in reduced insulin secretion from the pancreas with diabetes usually occurring in their early 20s. Of note, patients with this subtype of diabetes are usually slim and especially sensitive to sulphonylureas which are the drug of choice, although the condition does progress to requiring other agents including insulin. CVD risk is also raised. The other major subtype, Glucokinase influences the ‘glucose sensor’ within the pancreas resulting in reduced insulin secretion for a given blood glucose and mild chronic hyperglycaemia, typically from birth. Complications are rare and as a result, no specific treatment is required apart from during pregnancy (due to the impact of hyperglycaemia on the foetus). Although clinical suspicion needs to be high, early identification is clearly of benefit both for the patient and family members.
Dr Mark Freeman
The genetic architecture of type 2 diabetes
Christian Fuchsberger et al. Nature. Doi:10.1038/nature18642
Diabetes was famously referred to as the ‘geneticist’s nightmare’ in 1976. Although familial clustering of diabetes was well known, the pattern of inheritance did not conform to that of a dominant or recessive trait. The potential for genetic dissection had been boosted by the identification of HLA genes in type 1 diabetes, cementing the long recognised clinical description of at least two distinct forms of disease. Then, during the 1990’s genes for monogenic forms of diabetes (termed MODY) were identified. But where are we with the genetic predisposition for type 2 diabetes (T2DM)? This manuscript suggests not a good place. The authors conclude that their massive genotyping endeavor does not support the idea that lower-frequency variants have a major role in predisposition to T2DM. Numerous small gene effects have previously been reported to predispose to T2DM but none of them have led to new therapies nor can they be used as predictive markers. Given the well-known environmental factors which predispose to T2DM, perhaps R&D funds would be better directed to their reversal rather than pursuing the nightmare?
Long-term excess mortality associated with diabetes following acute myocardial infarction
O A Alabas et al. Journal of Epidemiology & Community Health. Doi:10.1136/jech-2016-207402
It is well known that type 2 diabetes is associated with an increased risk of cardiovascular disease and acute myocardial infarction (AMI) is an important manifestation of this. Indeed, fatal and non-fatal AMI is included in the primary composite end-point for the cardiovascular outcome studies, now mandated for all new diabetes medicines. This publication examines the long-term excess risk of death associated with diabetes following AMI using data from the MINAP study, based in the UK. Between 2003-13, there were more than 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes. All-cause mortality was higher among patients with diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a significant 72% excess risk of death following ST elevation AMI (and 67% for Non-STEMI). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity and cardiovascular treatments. These results provide an updated, UK confirmation of the importance of AMI in patients with diabetes, highlighting the potential benefits of antidiabetic agents which reduce this end-point.
Long-term pioglitazone treatment for patients with nonalcoholic steatohepatitis and prediabetes or type 2 diabetes mellitus
Kenneth Cusi et al. Annals of Internal Medicine. Doi:10.7326/M15-1774
Nonalcoholic fatty liver disease (NAFLD) is said to be reaching epidemic proportions worldwide and most patients with type 2 diabetes (T2DM) are thought to have this condition. Indeed, many T2DM patients are at risk of the more severe nonalcoholic steatohepatitis (NASH) even if they have normal liver aminotransferase levels. The argument goes that therapies for T2DM should be prioritized if they have a beneficial impact on NAFLD. This study examined 101 subjects with prediabetes or T2DM and biopsy-proven NASH. All were prescribed a hypocaloric diet and then randomly assigned to pioglitazone (45mg OD), or placebo for 18 months, followed by 18-month open-label pioglitazone. The primary outcome of improvement in liver histology was achieved in 58% and 51% had resolution of NASH. One of the difficulties in interpreting these studies is how to tease out the impact of improved glycaemic control from that of the specific drug. Having said that, some recent data suggest that sitagliptin was no more effective at reducing NAFLD than placebo. So, a come-back for pioglitazone? Perhaps it will be led by the gastroenterologists….
Trends in hospital admissions for hypoglycaemia in England: a retrospective, observational study
Francesco Zaccardi et al. The Lancet Diabetes & Endocrinology. Doi: http://dx.doi.org/10.1016/S2213-8587(16)30091-2
The recent National Diabetes In-patient audit continues to show that rates of hypoglycaemia remain an issue both for patients in hospital and also as a reason for admission. However, given the education provided to patients at diagnosis and during follow up around hypoglycaemia management, the expectation would be that self-treatment should reduce admissions. Using the hospital episode statistics database, this retrospective study showed that 72% of the 101475 admissions over a 10-year period for hypoglycaemia occurred in patients aged over 60 with 18% having multiple admissions. Furthermore, over the 10 years, admissions for hypoglycaemia increased by 39% although when the increase in the prevalence of diabetes was taken into consideration, there was a reduction in admission rates. Given the rise in diabetes prevalence, aging population and the need to reduce unnecessary admissions, the appreciation of hypoglycaemia awareness and prevention should be given more attention.
Intensive treatment and severe hypoglycaemia among adults with type 2 diabetes
Rozalina G. McCoyet al. JAMA Internal Medicine. Doi:10.1001/jamainternmed.2016.2275
The UKPDS study demonstrated the benefit of glucose lowering in Type 2 Diabetes (T2DM), a fact reinforced by its legacy study. However, other evidence from ACCORD/ ADVANCE and VADT did raise concerns about intensive glucose lowering especially in patients at higher risk of cardiovascular disease. NICE guidance goes some way in acknowledging this with its messages of individualised glucose targets. This study seems to reinforce the potential problems associated with tight glycaemic control. Looking at >31000 patients who achieved and maintained an HbA1c <7.0% (53mmol/mol), it compared high complexity patients (aged >75years, dementia or end stage renal failure or 3 or more long term conditions) with low intensity patients. Complex patients requiring intensive (aiming for lower than recommended HbA1c targets) had double the frequency of severe hypoglycaemia. The authors calculated that more than 20% of patients with T2DM received unnecessarily intensive treatment. These results further highlight the risk and significance of hypoglycaemia in complex patients which at best is likely to outweigh any perceived benefit of improved control and at worse result in harm to patients.
NGT subjects with late insulin responses had defective early insulin secretion and were at higher risk of developing diabetes. Insulin secretion patterns could be a useful T2D predictor in the Chinese population (Journal of Diabetes and Its Complications)
The majority of children who present with clinical type 1 diabetes are of school age; however 80% of children who develop type 1 diabetes by 18 years of age will have detectable islet autoantibodies by 3 years of age. The evolving concept that type 1 diabetes in many children has developmental origins has directed research questions in search of prevention back to pregnancy and early life. (Pediatric Diabetes)
The fast emerging field of immunometabolism underpins the pathogenesis of metabolic diseases like T2DM and CAD. Understanding the immune-metabolic interface is daunting (Journal of Diabetes Research)
A substantial number of patients with newly diagnosed type 2 diabetes fail to undergo intensification of therapy within 6 months of metformin monotherapy failure. Early intervention in patients when metformin monotherapy failed resulted in more rapid attainment of A1C goals (Diabetes Care)
There were no pronounced differences in effectiveness and long-term cardiovascular safety and mortality between the DAIs, although there were some differences in clinical characteristics between patients using the three types of insulin (Diabetes Therapy)
The definitive audit was launched in the summer of 2014 and it has recently published its first foot report (Diabetic Medicine)
A review of the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate cardiovascular outcome trials findings into clinical practice (Cardiovascular Diabetology)
These results have established for the first time that multiple, DFU-derived fibroblast cell lines can be reprogrammed with efficiencies similar to control fibroblasts, thus demonstrating their utility for future regenerative therapy of DFUs (Cellular Reprogramming)
The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained (Journal of Diabetes Research)
Markers of metabolic syndrome and hyperglycemia predicted decreased IS in T2D youth. Paradoxically, hypoglycemia predicted decreased IS in T1D youth and hyperglycemia, particularly overnight, predicted improved IS. These preliminary results imply different mechanisms underlying IR in T1D vs T2D and suggest a role for non-insulin therapies in T1D to improve IR (Pediatric Diabetes)
The finding that depressed mood predicted both low health literacy and low diabetes self-management stresses the importance of screening for depression. Increasing people’s understanding of diabetes self-management and supporting those with depression are crucial to enhance participation in diabetes self-management (Journal of Diabetes Research)
Sensor-augmented pump therapy with predictive low glucose management reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting (Diabetes Technology and Therapeutics)
Risk of lactic acidosis was higher in metformin users than in other glucose-lowering agent users, and increased with decreasing eGFR, although this could be attributable to surveillance bias; however, diagnosed lactic acidosis was rare and can occur regardless of renal function (Diabetic Medicine)
This article will explore the mode of action of currently available oral treatments, factors to consider when individualizing HbA1c targets, the relevance of estimated glomerular filtration rate assessment, and the importance of reviewing the clinical impact of all treatment decisions (Diabetes Therapy)
Stepwise diabetes prevention in people with prediabetes can effectively reduce diabetes incidence by a third in community settings; however, people with iIFG may require different interventions (Diabetes Care)