Prevalence, glucose control and relative survival of people with Type 2 diabetes in the UK from 1991 to 2013.

AIMS: To characterize the prevalence of Type 2 diabetes between 1991 and 2013 in the UK and to determine whether corresponding glucose control and survival had changed in the diabetic population during this period. METHODS: For this retrospective cohort study, people diagnosed with Type 2 diabetes between 1991 and 2013 were identified from the Clinical Practice Research Datalink (CPRD) and the annual point prevalence calculated. Mean HbA1c by year was estimated. The Cox proportional hazards model was used to calculate the risk of all-cause mortality by year for incident cases of Type 2 diabetes treated with glucose-lowering therapy. RESULTS: Crude prevalence of diagnosed Type 2 diabetes increased from 1.32% [95% confidence interval (95% CI) 1.30% to 1.34%] in 1991 to 4.54% (4.52% to 4.56%) in 2013. Mean HbA1c for people with diagnosed Type 2 diabetes was 71 mmol/mol (8.6%) in 1991, 59 mmol/mol (7.5%) in 2003 and 58 mmol/mol (7.5%) in 2013. For diagnosed Type 2 diabetes treated with glucose-lowering therapy, when compared with 1991, the hazard ratio for all-cause mortality was 0.33 (0.27-0.41) in 2013. CONCLUSION: The prevalence of diagnosed Type 2 diabetes trebled in the UK between 1991 and 2013. Improved survival in people with diagnosed Type 2 diabetes is likely to account, at least in part, for the increase in prevalence observed.

Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer.

AIMS: To evaluate the association between insulin exposure and all-cause mortality, incident major adverse cardiovascular events (MACE) and incident cancer in people with type 2 diabetes treated with insulin monotherapy. METHODS: For this retrospective study, people with type 2 diabetes who progressed to insulin monotherapy from the year 2000 were identified from the UK Clinical Practice Research Datalink. The risks of progression to serious adverse outcomes were compared using Cox proportional hazards models. In the main analysis, insulin exposure was introduced into the model as prescribed international units per kilogram per day, as a cumulative, continuous, annually updated, time-dependent covariable. RESULTS: A total of 6484 subjects with type 2 diabetes who progressed to treatment with insulin monotherapy from the year 2000 onwards were followed for a mean of 3.3 years. The event numbers were as follows: deaths, n = 1110; incident MACE, n = 342; incident cancers, n = 382. Unadjusted event rates were 61.3 deaths per 1000 person-years, 26.4 incident MACE per 1000 person-years and 24.6 incident cancers per 1000 person-years. The adjusted hazard ratios in relation to 1-unit increases in insulin dose were 1.54 [95% confidence interval (CI) 1.32-1.78] for all-cause mortality, 1.37 (95% CI 1.05-1.81) for MACE and 1.35 (95% CI 1.04-1.75) for cancer. CONCLUSIONS: There was an association between increasing exogenous insulin dose and increased risk of all-cause mortality, MACE and cancer in people with type 2 diabetes. The limitations of observational studies mean that this should be further investigated using an interventional study design.

Mortality risk with sulphonylureas compared to metformin.

Current clinical guidelines in the USA and the UK recommend first-line glucose-lowering treatment with metformin monotherapy for glucose control in type 2 diabetes, where not contraindicated. Consequently, the proportion of people treated with sulphonylureas is decreasing. The purpose of this commentary is to discuss the risks and benefits associated with sulphonylurea monotherapy versus metformin monotherapy and the evidence that, in comparison with metformin, sulphonylureas cause increased harm to people with type 2 diabetes.

How many people inject insulin? UK estimates from 1991 to 2010.

AIMS: We set out to estimate the prevalence rate of insulin use in the UK population, the total number of people in the UK who use insulin, the proportion of users with type 1 and type 2 diabetes and changes between 1991 and 2010. METHODS: Patients receiving prescriptions for insulin were identified in the Clinical Practice Research Datalink and attributed a diagnosis of type 1 or type 2 diabetes. The annual prevalence of insulin use was calculated and applied to population data. RESULTS: The crude prevalence rate of insulin use increased from 2.43 (95% CI 2.38-2.49) per 1000 population in 1991 to 6.71 (6.64-6.77) per 1000 in 2010. The largest change was an increase in the prevalence of insulin users with a diagnosis of type 2 diabetes from 0.67 (0.64-0.70) to 4.34 (4.29-4.39) per 1000 population. The absolute number using insulin increased from 137 000 people (121 000-155 000) in 1991 to 421 000 (400 000-444 000) in 2010. The proportion taking insulin alone (as against combination with oral agents) decreased from 97% in the first decade to 37% in the second. CONCLUSION: The number of people using insulin trebled between 1991 and 2010, largely due to a considerable increase in the number of people with type 2 diabetes using insulin.

Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality.

AIMS: To compare the risk of major adverse cardiovascular events (MACE) and mortality for combination therapies with metformin and either sulphonylurea (SU) or dipeptidyl peptidase-4 inhibitor (DPP-4i). METHODS: Data were from the UK Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with combination therapies comprising metformin plus SU or DPP-4i 2007-2012. The co-primary endpoints were all-cause mortality and MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score. RESULTS: A total of 33 983 patients were prescribed SU and 7864 DPP-4i, and 5447 patients in each cohort could be matched directly and 6901 by propensity score. In the main analysis, there were 716 MACE events and 1217 deaths. Crude event rates for MACE were 11.3 events per 1000 person-years (pkpy) for SU, versus 5.3 pkpy for DPP-4i. For all-cause mortality, rates were 16.9 versus 7.3 pkpy, respectively. Following adjustment, there was a significant increase in the adjusted hazard ratio (aHR) for all-cause mortality in those exposed to SU across all analytical models: aHR = 1.357 (95% CI 1.076-1.710) for all subjects, 1.850 (1.245-2.749) directly matched and 1.497 (1.092-2.052) propensity-matched. For MACE, aHR was 1.710 (1.280-2.285) for all subjects, 1.323 (0.832-2.105) directly matched and 1.547 (1.076-2.225) propensity-matched. CONCLUSIONS: There was a reduction in all-cause mortality for patients treated with metformin combined with DPP-4i versus metformin plus SU, and a similar trend for MACE.

Association between first-line monotherapy with sulphonylurea versus metformin and risk of all-cause mortality and cardiovascular events: a retrospective, observational study.

AIMS: To evaluate the risk of all-cause mortality and major adverse cardiovascular events (MACE) for patients exposed to first-line monotherapy with sulphonylurea or metformin. METHODS: Data were from the Clinical Practice Research Datalink (CPRD). Patients with type 2 diabetes were selected if initiated with metformin or sulphonylurea monotherapy as their first-line glucose-lowering regimen 2000-2012. The primary endpoint was all-cause mortality; the secondary endpoint was MACE (myocardial infarction or stroke). Times to endpoints were compared using Cox proportional hazards models. Additional analyses were performed on subsets matched directly on key characteristics and by propensity score. RESULTS: In the main analysis, 76 811 patients were prescribed metformin monotherapy (mean follow-up 2.9 years) and 15 687 sulphonylurea monotherapy (mean follow-up 3.1 years). A total of 2604 patients were included in each arm of the directly matched cohorts and 8836 in the propensity-matched. With respect to all-cause mortality, using all three analytical approaches the hazard ratio (HR) was significantly increased for sulphonylurea compared with metformin: adjusted HR = 1.580 (95% CI 1.483-1.684) for the main analysis, 1.902 (1.733-2.088) for those matched on propensity score, and 1.272 (1.021-1.584) for the directly matched cohort analysis. For MACE, the respective HRs were 1.196 (1.090-1.313), 1.202 (1.001-1.442) and 0.814 (0.578-1.148), respectively. CONCLUSIONS: All-cause mortality was significantly increased in patients prescribed sulphonylurea compared with metformin monotherapy. Whilst residual confounding and confounding by indication may remain, this study indicates that first-line treatment with sulphonylurea monotherapy should be reconsidered.

Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls.

AIMS: Clinical and observational studies have shown an increased risk of cardiovascular events and death associated with sulphonylureas versus metformin. However, it has never been determined whether this was due to the beneficial effects of metformin or detrimental effects of sulphonylureas. The objective of this study was therefore to compare all-cause mortality in diabetic patients treated first-line with either sulphonylurea or metformin monotherapy with that in matched individuals without diabetes. METHODS: We used retrospective observational data from the UK Clinical Practice Research Datalink (CPRD) from 2000. Subjects with type 2 diabetes who progressed to first-line treatment with metformin or sulphonylurea monotherapy were selected and matched to people without diabetes. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables. RESULTS: We identified 78,241 subjects treated with metformin, 12,222 treated with sulphonylurea, and 90,463 matched subjects without diabetes. This resulted in a total, censored follow-up period of 503,384 years. There were 7498 deaths in total, representing unadjusted mortality rates of 14.4 and 15.2, and 50.9 and 28.7 deaths per 1000 person-years for metformin monotherapy and their matched controls, and sulphonylurea monotherapy and their matched controls, respectively. With reference to observed survival in diabetic patients initiated with metformin monotherapy [survival time ratio (STR) = 1.0], adjusted median survival time was 15% lower (STR = 0.85, 95% CI 0.81-0.90) in matched individuals without diabetes and 38% lower (0.62, 0.58-0.66) in diabetic patients treated with sulphonylurea monotherapy. CONCLUSIONS: Patients with type 2 diabetes initiated with metformin monotherapy had longer survival than did matched, non-diabetic controls. Those treated with sulphonylurea had markedly reduced survival compared with both matched controls and those receiving metformin monotherapy. This supports the position of metformin as first-line therapy and implies that metformin may confer benefit in non-diabetes. Sulphonylurea remains a concern.

Geriatric assessment and medical preoperative screening (GrAMPS) program for older hernia patients.

PURPOSE: The incidence of older adults undergoing inguinal and ventral hernia repairs is increasing. Older adults are disproportionately affected by age-related risk factors, which are often under-recognized and may adversely affect surgical outcomes. These age-related risk factors often termed "geriatric syndromes," include multimorbidity, frailty, cognitive impairment, depression, obesity, functional impairment, polypharmacy, and poor subjective health. The aim of this study was to identify the prevalence of age-related risk factors in older patients undergoing elective hernia repair. METHODS: Patients aged 60 years or older with a planned elective surgical repair of a ventral or inguinal hernia were prospectively enrolled in a clinic. Subjects completed several validated screening tools for geriatric syndromes. RESULTS: Seventy patients completed preoperative assessments (mean age: 68.5 years). In total, 24 (34.3%) screened positive for previously unrecognized objective cognitive impairment (Mini-Cog) and 33 (47.1%) for a subjective memory concern. Sixty patients (85.7%) met criteria for polypharmacy. Additionally, 48 (68.6%) screened positive for either pre-frailty (37, 52.9%) or frailty (11, 15.7%), and 66 (94.3%) had multimorbidity. Twenty-five (35.7%) patients self-rated their health as "poor" or "fair," and 18 (25.7%) patients endorsed some functional impairment. CONCLUSIONS: There is a high prevalence of age-related risk factors in older patients undergoing elective hernia repair. Further, these factors are often unrecognized and underappreciated despite their potential to significantly impact informed consent and shared decision making. Additional study is required to define the impact of these age-related risk factors on surgical outcomes, which will inform preoperative risk assessment and optimization through modifiable risk reduction.

Randomized control trial evaluating the use of a shared decision-making aid for older ventral hernia patients in the Geriatric Assessment and Medical Preoperative Screening (GrAMPS) Program.

PURPOSE: Shared decision making (SDM) is ideally suited to abdominal wall surgery in older adults given the breadth of decision making required by the hernia surgeon and the impact on quality of life (QOL) by various treatment options. Given the paucity of literature surrounding SDM in hernia patients, the feasibility of a novel, formalized SDM aid/tool was evaluated in a pilot randomized trial. METHODS: Patients 60 years or older with a diagnosed ventral hernia were prospectively randomized at an academic hernia center. In the experimental arm, a novel SDM tool, based on the SHARE Approach, guided the consultation. Previously validated SDM assessments and patient's hernia knowledge retention was measured. RESULTS: Eighteen (18) patients were randomized (9 control and 9 experimental). Cohorts were well matched in age (p = 0.51), comorbidities (Charlson Comorbidity Score: p = 0.43) and frailty (mFI-11: p = 0.19; Risk Analysis Index: p = 0.33). Consultation time was 11 min longer in the experimental cohort (p < 0.01). There was a trend towards better Decisional Conflict Scores in the experimental group (p = 0.25) and the experimental cohort had improved post-visit retained hernia knowledge (p < 0.01). All patients in the experimental arm (100%) enjoyed working through the SDM aid/tool and felt it was a worthwhile exercise. CONCLUSION: Incorporating a formalized SDM tool into a busy hernia surgical practice is feasible and well received by patients. In addition, early results suggest it improves retention of basic hernia knowledge and may reduce patient's decisional conflict. Next steps include condensing the SDM tool to enhance efficiency within the clinic and beginning a large, randomized control trial.