HbA_1c variability is associated with increased mortality and earlier hospital admission in people with Type 1 diabetes

Aim: Despite evidence of morbidity, no evidence exists on the relationship between HbA1c variability and mortality in Type 1 diabetes. We performed an observational study to investigate whether the association between HbA1c variability and mortality exists in a population of people with Type 1 diabetes. As a secondary outcome, we compared onset of first hospital admission between groups. Methods: People with Type 1 diabetes were identified for inclusion from the Scottish Care Information – Diabetes data set. This database includes data of all people known to have diabetes who live within Scotland. A survival analysis was carried out over a 47‐month period comparing two groups; group 1 with a HbA1c coefficient of variation (CV) above the median CV value, and group 2 with a CV below the median value. Time to death or first admission was also analysed. A Cox proportional hazard model was used to compare time to death, adjusting for appropriate covariables. Results: Some 6048 individuals with Type 1 diabetes were included in the analysis. Median HbA1c CV was 7.9. The hazard ratio (HR) for mortality for those with an HbA1c CV above the median value is 1.5 over 47 months of follow‐up (P < 0.001). HR for survival to either the first admission to hospital or death for those with an HbA1c CV above the median value was 1.35 (95% confidence interval 1.25–1.45) over 730 days of follow‐up (P < 0.001). Conclusion: Our results show that people with greater HbA1c variability have a higher rate of mortality and earlier hospital admission in Type 1 diabetes

Predictive Clinical Parameters for the Therapeutic Efficacy of Sitagliptin in Korean Type 2 Diabetes Mellitus

BackgroundSitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects.MethodsWe obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks.ResultsWe classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group.ConclusionIn Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders

An observational study of patient characteristics and mortality following hypoglycemia in the community

Objectives: Characterize diabetes patients with severe hypoglycemia requiring emergency services intervention at home and investigate 12 month mortality. Research design and methods: Emergency services call-outs for hypoglycemia were recorded between 2005 and 2013 in an area covering 34000 patients with diabetes. Patient characteristics were documented together with capillary blood glucose (CBG), HbA1c and treatment for hypoglycemia. 12 month mortality and variables influencing survival were analysed. Results: In 1835 episodes amongst 1156 patients, 45% had type 1 diabetes (68.2% males), 44% had type 2 diabetes (49.4% males) with a minority unclassified. CBG at presentation (mean±SD) was 1.76±0.72 mmol/L in type 1 diabetes and 1.96±0.68 mmol/L in type 2 diabetes patients (p<0·0001), with higher HbA1c in the former group (8.3±1.52% (67.5±16.4 mmol/mol) and 7.8±1.74% (61.6±19.0 mmol/mol), respectively; p<0·0001). A third of type 2 diabetes patients were not on insulin therapy and displayed lower HbA1c compared with insulin users. Glucagon was used in 37% of type 1 diabetes and 28% of type 2 diabetes patients (p<0.0001). One year mortality was 4.45% in type 1 diabetes and 22.1% in type 2 diabetes. Age and type of diabetes were predictive of mortality in multivariable analysis, whereas CBG levels/frequency of hypoglycemia had no effect. Conclusions: Severe hypoglycemia in the community is common with a male predominance in type 1 diabetes. Severe hypoglycemia in non-insulin treated type 2 diabetes patients is associated with lower HbA1c compared with insulin users. Severe hypoglycemia appears to be associated with increased mortality at 12 months, particularly in type 2 diabetes. KEY MESSAGES Severe hypoglycemia in the community is common, and presents a large burden on both patients and healthcare workers. Using a large database of ambulance call-outs for hypoglycemia this study aimed to characterise those requiring the emergency services for an episode of hypoglycemia, and to investigate factors that may be associated with an increased risk of mortality. We found that a third of type 2 diabetes patients having severe hypoglycemic episodes were not using any insulin, these individuals had a lower HbA1c than those with type 2 diabetes requiring insulin treatment. 12 month mortality following an episode of severe hypoglycemia was high, especially in individuals with type 2 diabetes. More research is required to investigate the cause of death in these patient

Heritability of Proliferative Diabetic Retinopathy

OBJECTIVE—Diabetic nephropathy clusters in families, suggesting that genetic factors play a role in its pathogenesis. We investigated whether similar clustering exists for proliferative retinopathy in families with two or more siblings with type 1 diabetes

The Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE): study protocol for a cluster randomised controlled trial

Introduction People with type 1 diabetes (T1DM) require insulin therapy to sustain life, and need optimal glycaemic control to prevent diabetic ketoacidosis and serious long-term complications. Insulin is generally administered using multiple daily injections but can also be delivered using an infusion pump (continuous subcutaneous insulin infusion), a more costly option with benefits for some patients. The UK National Institute for Health and Care Excellence (NICE) recommend the use of pumps for patients with the greatest need, citing insufficient evidence to approve extension to a wider population. Far fewer UK adults use pumps than in comparable countries. Previous trials of pump therapy have been small and of short duration and failed to control for training in insulin adjustment. This paper describes the protocol for a large randomised controlled trial comparing pump therapy with multiple daily injections, where both groups are provided with high-quality structured education. Methods and analysis A multicentre, parallel group, cluster randomised controlled trial among 280 adults with T1DM. All participants attended the week-long dose adjustment for normal eating (DAFNE) structured education course, and receive either multiple daily injections or pump therapy for 2 years. The trial incorporates a detailed mixed-methods psychosocial evaluation and cost-effectiveness analysis. The primary outcome will be the change in glycosylated haemoglobin (HbA1c) at 24 months in those participants whose baseline HbA1c is at or above 7.5% (58 mmol/mol). The key secondary outcome will be the proportion of participants reaching the NICE target of an HbA1c of 7.5% (58 mmol/mol) or less at 24 months. Ethics and dissemination The protocol was approved by the Research Ethics Committee North West, Liverpool East and received Medicines and Healthcare products Regulatory Agency (MHRA) clinical trials authorisation. Each participating centre gave National Health Service R&D approval. We shall disseminate study findings to study participants and through peer reviewed publications and conference presentations, including lay user groups. Trial registration number ISRCTN 61215213

Complication characteristics between young-onset type 2 versus type 1 diabetes in a UK population.

BACKGROUND: In the UK, the care of young people with diabetes has focused predominantly on type 1 diabetes (T1D). However, young-onset T2D has become increasingly prevalent. At present, it is unclear which type of diabetes represents the more adverse phenotype to develop complications. This study aims to determine the complication burden and its predictive factors in young-onset T2D compared with T1D. METHODS: A cross-sectional study using a hospital diabetes register to identify patients with young-onset T2D and T1D. Young-onset T2D was defined as age of diagnosis below 40 years. The T1D cohort with a similar age of diagnosis was used as a comparator. Data from the last clinic visit was used for analysis. Clinical characteristics and diabetes complications were evaluated at diabetes durations 20 years. Predictive factors for diabetes complications (age, sex, glycated hemoglobin, creatinine, diabetes duration, hypertension, dyslipidemia, and body mass index >25) were determined by logistic regression analysis. RESULTS: Data were collected on 1287 patients, of which 760 and 527 had T1D and T2D, respectively. In all diabetes durations, the T2D cohort had an older age of onset (p<0.0005) with a higher prevalence of obesity, hypertension, and dyslipidemia (all p<0.0005) while glycemic control was similar in both groups. Cardiovascular disease (p<0.005) and neuropathy (p<0.05) were more prevalent in the young-onset T2D cohort in all diabetes durations. There was no difference in retinopathy. Cardiovascular disease was predominantly due to ischemic heart disease. Stroke and peripheral vascular disease became significantly higher in T2D after 20 years duration. After controlling for traditional risk factors, young-onset T2D was an independent predictor for cardiovascular disease (p<0.005) and neuropathy (p<0.05) but not for retinopathy. CONCLUSIONS: Young-onset T2D is a more aggressive phenotype than T1D to develop diabetes complications, particularly for ischemic heart disease and neuropathy

A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia

AIM: Hypoglycaemia in Type 1 diabetes is associated with mortality and morbidity, especially where awareness of hypoglycaemia is impaired. Clinical pathways for access to continuous glucose monitoring (CGM) and flash glucose monitoring technologies are unclear. We assessed the impact of CGM and flash glucose monitoring in a high-risk group of people with Type 1 diabetes. METHODS: A randomized, non-masked parallel group study was undertaken. Adults with Type 1 diabetes using a multiple-dose insulin-injection regimen with a Gold score of ≥ 4 or recent severe hypoglycaemia were recruited. Following 2 weeks of blinded CGM, they were randomly assigned to CGM (Dexcom G5) or flash glucose monitoring (Abbott Freestyle Libre) for 8 weeks. The primary outcome was the difference in time spent in hypoglycaemia (below 3.3 mmol/l) from baseline to endpoint with CGM versus flash glucose monitoring. RESULTS: Some 40 participants were randomized to CGM (n = 20) or flash glucose monitoring (n = 20). The participants (24 men, 16 women) had a median (IQR) age of 49.6 (37.5-63.5) years, duration of diabetes of 30.0 (21.0-36.5) years and HbA1c of 56 (48-63) mmol/mol [7.3 (6.5-7.8)%]. The baseline median percentage time < 3.3 mmol/l was 4.5% in the CGM group and 6.7% in the flash glucose monitoring. At the end-point the percentage time < 3.3 mmol/l was 2.4%, and 6.8% respectively (median between group difference -4.3%, P = 0.006). Time spent in hypoglycaemia at all thresholds, and hypoglycaemia fear, were different between groups, favouring CGM. CONCLUSION: CGM more effectively reduces time spent in hypoglycaemia in people with Type 1 diabetes and impaired awareness of hypoglycaemia compared with flash glucose monitoring. (Clinical Trial Registry No: NCT03028220)

One year of liraglutide treatment offers sustained and more effective glycaemic control and weight reduction compared with sitagliptin, both in combination with metformin, in patients with type 2 diabetes: a randomised, parallel-group, open-label trial

P>Aim: The aim of this study was to compare the efficacy and safety of once-daily human glucagon-like peptide-1 analogue liraglutide with dipeptidyl peptidase-4 inhibitor sitagliptin, each added to metformin, over 52 weeks in individuals with type 2 diabetes. Methods: In an open-label, parallel-group trial, metformin-treated participants were randomised to liraglutide 1.2 mg/day (n = 225), liraglutide 1.8 mg/day (n = 221) or sitagliptin 100 mg/day (n = 219) for 26 weeks (main phase). Participants continued the same treatment in a 26-week extension. Results: Liraglutide (1.2 or 1.8 mg) was superior to sitagliptin for reducing HbA(1c) from baseline (8.4-8.5%) to 52 weeks: -1.29% and -1.51% vs. -0.88% respectively. Estimated mean treatment differences between liraglutide and sitagliptin were as follows: -0.40% (95% confidence interval -0.59 to -0.22) for 1.2 mg and -0.63% (-0.81 to -0.44) for 1.8 mg (both p < 0.0001). Weight loss was greater with liraglutide 1.2 mg (-2.78 kg) and 1.8 mg (-3.68 kg) than sitagliptin (-1.16 kg) (both p < 0.0001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly more with liraglutide 1.8 mg than with sitagliptin (p = 0.03). Proportions of participants reporting adverse events were generally comparable; minor hypoglycaemia was 8.1%, 8.3% and 6.4% for liraglutide 1.2 mg, 1.8 mg and sitagliptin respectively. Gastrointestinal side effects, mainly nausea, initially occurred more frequently with liraglutide, but declined after several weeks. Conclusion: Liraglutide provides greater sustained glycaemic control and body weight reduction over 52 weeks. Treatment satisfaction was significantly greater with 1.8 mg liraglutide, similar to 26-week results. The safety profiles of liraglutide and sitagliptin are consistent with previous reports

Day-to-day fasting self-monitored blood glucose variability is associated with risk of hypoglycaemia in insulin-treated patients with type 1 and type 2 diabetes: a post hoc analysis of the SWITCH trials

AIMS: To investigate the association between day-to-day fasting self-monitored blood glucose (SMBG) variability and risk of hypoglycaemia in type 1 (T1D) and type 2 diabetes (T2D), and compare day-to-day fasting SMBG variability between treatments with insulin degludec (degludec) and insulin glargine 100 units/mL (glargine U100). MATERIALS AND METHODS: Data were retrieved from two double-blind, randomised, treat-to-target, two-period (32 weeks each) crossover trials of degludec versus glargine U100 in T1D (SWITCH 1, n=501) and T2D (SWITCH 2, n=720). Available fasting SMBGs were used to determine the standard deviation (SD) of day-to-day fasting SMBG variability for each patient and treatment combination. The association between day-to-day fasting SMBG variability and overall symptomatic, nocturnal symptomatic and severe hypoglycaemia was analysed for the pooled population using linear regression, and with fasting SMBG variability included as a three-level factor defined by population tertiles. Finally, day-to-day fasting SMBG variability was compared between treatments. RESULTS: Linear regression showed that day-to-day fasting SMBG variability was significantly associated with overall symptomatic, nocturnal symptomatic, and severe hypoglycaemia risk in T1D and T2D (p<0.05). Day-to-day fasting SMBG variability was significantly associated (p<0.01) with all categories of hypoglycaemia risk, except for severe hypoglycaemia in T2D when analysed within tertiles. Degludec was associated with 4% lower day-to-day fasting SMBG variability than glargine U100 in T1D (p=0.0082) and 10% lower in T2D (p<0.0001). CONCLUSIONS: Higher day-to-day fasting SMBG variability is associated with an increased risk of overall symptomatic, nocturnal symptomatic and severe hypoglycaemia. Degludec has significantly lower day-to-day fasting SMBG variability versus glargine U100. This article is protected by copyright. All rights reserved