Prevalence and Incidence of Hypoglycaemia in 532,542 People with Type 2 Diabetes on Oral Therapies and Insulin: A Systematic Review and Meta-Analysis of Population Based Studies.
ABSTRACT: To collate and evaluate the current literature reporting the prevalence and incidence of hypoglycaemia in population based studies of type 2 diabetes.Medline, Embase and Cochrane were searched up to February 2014 to identify population based studies reporting the proportion of people with type 2 diabetes experiencing hypoglycaemia or rate of events experienced. Two reviewers independently screened studies for eligibility and extracted data for included studies. Random effects meta-analyses were carried out to calculate the prevalence and incidence of hypoglycaemia.46 studies (n = 532,542) met the inclusion criteria. Prevalence of hypoglycaemia was 45% (95%CI 0.34,0.57) for mild/moderate and 6% (95%CI, 0.05,0.07) for severe. Incidence of hypoglycaemic episodes per person-year for mild/moderate and for severe was 19 (95%CI 0.00, 51.08) and 0.80 (95%CI 0.00,2.15), respectively. Hypoglycaemia was prevalent amongst those on insulin; for mild/moderate episodes the prevalence was 50% and incidence 23 events per person-year, and for severe episodes the prevalence was 21% and incidence 1 event per person-year. For treatment regimes that included a sulphonylurea, mild/moderate prevalence was 30% and incidence 2 events per person-year, and severe prevalence was 5% and incidence 0.01 events per person-year. A similar prevalence of 5% was found for treatment regimes that did not include sulphonylureas.Current evidence shows hypoglycaemia is considerably prevalent amongst people with type 2 diabetes, particularly for those on insulin, yet still fairly common for other treatment regimens. This highlights the subsequent need for educational interventions and individualisation of therapies to reduce the risk of hypoglycaemia.
Project description:<h4>Aims</h4>Hypoglycaemia is a serious medical emergency. The need for emergency medical service care and the costs of hypoglycaemic emergencies are not completely known.<h4>Methods</h4>This was a retrospective observational study using Public Company for Health Emergencies (EPES) data for hypoglycaemia in 2012. The EPES provides emergency medical services to the entire population of Andalusia, Spain (8.5 million people). Data on event type, onsite treatments, emergency room visits or hospitalization were collected. Medical costs were estimated using the public rates for healthcare services.<h4>Results</h4>From a total of 1 137 738 emergency calls that requested medical assistance, 8683 had a primary diagnosis of hypoglycaemia (10.34 per 10 000 person-years). The incidence of severe hypoglycaemic episodes requiring emergency treatment in the estimated population with diabetes was 80 episodes per 10 000 person-years. A total of 7479 episodes (86%) required an emergency team to visit the patient's residence. The majority of cases (64%) were addressed in the residence, although 1784 (21%) cases were transferred to hospital. A total of 5564 events (65%) involved patients aged > 65 years. Overall mortality was 0.32% (28 cases). The total annual cost of attending a hypoglycaemic episode was €6 093 507, leading to an estimated mean direct cost per episode of €702 ± 565. Episodes that required hospital treatment accounted for 49% of the total costs.<h4>Conclusions</h4>Hypoglycaemia is a common medical emergency that is associated with high emergency medical service utilization, resulting in a significant economic impact on the health system.
Project description:AIMS/HYPOTHESIS:The aim of this study was to determine whether random non-fasting C-peptide (rCP) measurement can be used to assess hypoglycaemia risk in insulin-treated type 2 diabetes. METHODS:We compared continuous glucose monitoring-assessed SD of blood glucose and hypoglycaemia duration in 17 patients with insulin-treated type 2 diabetes and severe insulin deficiency (rCP < 200 pmol/l) and 17 matched insulin-treated control patients with type 2 diabetes but who had preserved endogenous insulin (rCP > 600 pmol/l). We then assessed the relationship between rCP and questionnaire-based measures of hypoglycaemia in 256 patients with insulin-treated type 2 diabetes and a comparison group of 209 individuals with type 1 diabetes. RESULTS:Continuous glucose monitoring (CGM)-assessed glucose variability and hypoglycaemia was greater in individuals with rCP < 200 pmol/l despite similar mean glucose. In those with low vs high C-peptide, SD of glucose was 4.2 (95% CI 3.7, 4.6) vs 3.0 (2.6, 3.4) mmol/l (p < 0.001). In the low-C-peptide vs high-C-peptide group, the proportion of individuals experiencing sustained hypoglycaemia ? 4 mmol/l was 94% vs 41% (p < 0.001), the mean rate of hypoglycaemia was 5.5 (4.4, 6.7) vs 2.1 (1.4, 2.9) episodes per person per week (p = 0.004) and the mean duration was 630 (619, 643) vs 223 (216, 230) min per person per week (p = 0.01). Hypoglycaemia ? 3 mmol/l was infrequent in individuals with preserved C-peptide (1.8 [1.2, 2.6] episodes per person per week vs 0.4 [0.1, 0.8] episodes per person per week for low vs high C-peptide, p = 0.04) and only occurred at night. In a population-based cohort with insulin-treated type 2 diabetes, self-reported hypoglycaemia was twice as frequent in those with rCP < 200 pmol/l (OR 2.0, p < 0.001) and the rate of episodes resulting in loss of consciousness or seizure was five times higher (OR 5.0, p = 0.001). The relationship between self-reported hypoglycaemia and C-peptide was similar in individuals with type 1 and type 2 diabetes. CONCLUSIONS/INTERPRETATION:Low rCP is associated with increased glucose variability and hypoglycaemia in patients with insulin-treated type 2 diabetes and represents a practical, stable and inexpensive biomarker for assessment of hypoglycaemia risk.
Project description:Insulin therapy is indicated for people with Type 1 diabetes mellitus; however, treatment-related weight gain and hypoglycaemia represent barriers to optimal glycaemic management. This study assessed the health economic value of maintained reductions in HbA1c , BMI and hypoglycaemia incidence among the UK Type 1 diabetes population.The Cardiff Type 1 Diabetes Model was used to estimate lifetime costs, life-years and quality-adjusted life-years (QALYs) for individuals with Type 1 diabetes at different baseline HbA1c , BMI and hypoglycaemic event rates. Results were discounted at 3.5%, and the net monetary benefit associated with improving Type 1 diabetes management was derived at £20 000/QALY gained. Per-person outputs were inflated to national levels using UK Type 1 diabetes prevalence estimates.Modelled subjects with an HbA1c of 86 mmol/mol (10.0%) were associated with discounted lifetime per-person costs of £23 795; £12 649 of which may be avoided by maintaining an HbA1c of 42 mmol/mol (6.0%). Combined with estimated QALY gains of 2.80, an HbA1c of 42 mmol/mol (6.0%) vs. 86 mmol/mol (10.0%) was associated with a £68 621 per-person net monetary benefit. Over 1 year, unit reductions in BMI produced £120 per-person net monetary benefit, and up to £197 for the avoidance of one non-severe hypoglyceamic event.Maintained reductions in HbA1c significantly alleviate the burden associated with Type 1 diabetes in the UK. Given the influence of weight and hypoglycaemia on health economic outcomes, they must also be key considerations when assessing the value of Type 1 diabetes technologies in clinical practice.
Project description:Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial.The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year.In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.
Project description:Acute diarrheal illness (ADI) is an important public health problem worldwide. We estimated the morbidity, distribution, and burden of self-reported ADI in China over the last three decades.We used the keywords "diarrhea and morbidity" to identify studies published in Chinese by searching CNKI, WANFANG, Chongqing VIP, and SinoMed. Studies published in English were identified using the keywords "diarrhea, morbidity, and China" to search Pubmed/Medline, Embase, and Cochrane Library Data. All articles published before Dec 31, 2014 were included in the search. Data were extracted and the pooled 2-week incidence rate of ADI was calculated using the fixed-effects or random-effects model according to statistical testing for homogeneity. The incidences of each subgroup (organized by age, location, study period) were also calculated. Publication bias was examined using Begg's test. Data manipulation and statistical analyses were undertaken using R-2.15.1 software.We estimated that the pooled 2-week prevalence of ADI in China was 2.04% (95% CI: 1.48-2.79) and that the corresponding incidence rate was 0.53 (95% CI: 0.38-0.73) episodes per person-year. The ADI rate was highest among children aged <?5 years (1.43 episodes per person-year), and it was slightly higher in males than in females (0.58 vs 0.52 episodes per person-year). From 1980 to 2012, there was a significant decrease in the incidence of ADI, from 0.82 to 0.48 episodes per person-year, but the ADI incidence was consistent over the last two decades. Additionally, the incidence of ADI was higher in rural areas and in west China and peaked in the summer months.The current study indicates that ADI caused a substantial disease burden in China in the last 30 years, especially in rural areas and west China, where sanitation conditions were relatively poor. These findings highlight the importance of further investigation of the specific causes of and effective preventive measures for ADI.
Project description:Combination therapies are now recommended to treat uncomplicated malaria. We used a longitudinal design to assess the incidence of malaria and compare the efficacies of 3 combination regimens in Kampala, Uganda.Children aged 1-10 years were enrolled from randomly selected households in 2004-05 and 2007, and were followed at least monthly through 2008. Insecticide-treated bednets (ITNs) were provided in 2006. Children were randomized upon their first episode, and then treated for all episodes of uncomplicated malaria with amodiaquine/sulfadoxine-pyrimethamine (AQ/SP), artesunate/amodiaquine (AS/AQ), or artemether/lumefantrine (AL). Risks of parasitological failure were determined for each episode of uncomplicated malaria and clinical parameters were followed. A total of 690 children experienced 1464 episodes of malaria. 96% of these episodes were uncomplicated malaria and treated with study drugs; 94% were due to Plasmodium falciparum. The rank order of treatment efficacy was AL > AS/AQ > AQ/SP. Failure rates increased over time for AQ/SP, but not the artemisinin-based regimens. Over the 4-year course of the study the prevalence of asymptomatic parasitemia decreased from 11.8% to 1.4%, the incidence of malaria decreased from 1.55 to 0.32 per person year, and the prevalence of anemia (hemoglobin <10 gm/dL) decreased from 5.9% to 1.0%. No episodes of severe malaria (based on WHO criteria) and no deaths were seen.With ready access to combination therapies and distribution of ITNs, responses were excellent for artemisinin-containing regimens, severe malaria was not seen, and the incidence of malaria and prevalence of parasitemia and anemia decreased steadily over time.isrctn.org ISRCTN37517549.
Project description:Hypoglycaemia is a feared experience for people with diabetes. We aimed to study the prevalence and causes of hypoglycaemia among Sri Lankans with diabetes.One thousand patients with diabetes attending a private sector diabetic clinic were interviewed using a structured questionnaire. Hypoglycaemic episodes within the preceding month were inquired and severity was graded according to clinical features and/or capillary blood glucose levels.Mean age 55.0 years (±?12.5), 58.6% were males, mean diabetes duration 10.6 years (±?8.1), mean FPG 7.48 mmol/l (±?2.79) and mean HbA1c 7.82% (±?1.71) (62 mmol/mol). Of them, 26.1%. (mild 20.7%, moderate 3.9%, and severe 1.5%) experienced symptomatic hypoglycaemia. Sudden change diet (46.7%), unaccustomed exercise (15.7%) and increase in antihyperglycaemic therapy dosage (14.9%) were the recognized causes. Cause was not recognized by 16.3%. Non-prescribed native food items accounted for hypoglycaemia in 16.9% of patients (Momordica charantia 54.5%, Costus speciosus 52.3%, Salacia prinoides 11.4%, Coccinia grandis 6.8%, Adenanthera pavonina 4.5%). Severity of hypoglycaemia was positively correlated to age and duration of diabetes but not to HbA1C.Hypoglycaemia is common among patients with diabetes. Patients need advice on regular diet and exercise. Consumption of non-prescribed native foods should be considered as a possible cause.
Project description:To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.Retrospective epidemiological analysis of data from the ACCORD trial. Setting Diabetes clinics, research clinics, and primary care clinics.Patients were eligible for the ACCORD study if they had type 2 diabetes, a glycated haemoglobin (haemoglobin A(1C)) concentration of 7.5% or more during screening, and were aged 40-79 years with established cardiovascular disease or 55-79 years with evidence of subclinical disease or two additional cardiovascular risk factors. Intervention Intensive (haemoglobin A(1C) <6.0%) or standard (haemoglobin A(1C) 7.0-7.9%) glucose control.Symptomatic, severe hypoglycaemia, manifest as either blood glucose concentration of less than 2.8 mmol/l (<50 mg/dl) or symptoms that resolved with treatment and that required either the assistance of another person or medical assistance, and all cause and cause specific mortality, including a specific assessment for involvement of hypoglycaemia.10 194 of the 10 251 participants enrolled in the ACCORD study who had at least one assessment for hypoglycaemia during regular follow-up for vital status were included in this analysis. Unadjusted annual mortality among patients in the intensive glucose control arm was 2.8% in those who had one or more episodes of hypoglycaemia requiring any assistance compared with 1.2% for those with no episodes (53 deaths per 1924 person years and 201 deaths per 16 315 person years, respectively; adjusted hazard ratio (HR) 1.41, 95% CI 1.03 to 1.93). A similar pattern was seen among participants in the standard glucose control arm (3.7% (21 deaths per 564 person years) v 1.0% (176 deaths per 17 297 person years); adjusted HR 2.30, 95% CI 1.46 to 3.65). On the other hand, among participants with at least one hypoglycaemic episode requiring any assistance, a non-significantly lower risk of death was seen in those in the intensive arm compared with those in the standard arm (adjusted HR 0.74, 95% 0.46 to 1.23). A significantly lower risk was observed in the intensive arm compared with the standard arm in participants who had experienced at least one hypoglycaemic episode requiring medical assistance (adjusted HR 0.55, 95% CI 0.31 to 0.99). Of the 451 deaths that occurred in ACCORD up to the time when the intensive treatment arm was closed, one death was adjudicated as definitely related to hypoglycaemia.Symptomatic, severe hypoglycaemia was associated with an increased risk of death within each study arm. However, among participants who experienced at least one episode of hypoglycaemia, the risk of death was lower in such participants in the intensive arm than in the standard arm. Symptomatic, severe hypoglycaemia does not appear to account for the difference in mortality between the two study arms up to the time when the ACCORD intensive glycaemia arm was discontinued.NCT00000620.
Project description:New direct-acting antivirals have the potential to transform the hepatitis C (HCV) treatment landscape, with rates of sustained viral response in excess of 90%. As these new agents are expensive, an important question is whether to focus on minimizing the consequences of severe liver disease, or reducing transmission via 'treatment as prevention'. A back-calculation model was used to estimate the impact of treatment of mild, moderate and compensated cirrhosis on incident cases of HCV-related end-stage liver disease/hepatocellular carcinoma (ESLD/HCC). In addition, a dynamic model was used to determine the impact on incidence and prevalence of chronic infection in people who inject drugs (PWID), the main risk group in England. Treating 3500 cirrhotics per year was predicted to reduce ESLD/HCC incidence from 1100 (95% CrI 970-1240) cases per year in 2015 to 630 (95% CrI 530-770) in 2020, around half that currently expected, although treating moderate-stage disease will also be needed to sustain this reduction. Treating mild-stage PWID was required to make a substantial impact on transmission: with 2500 treated per year, chronic prevalence/annual incidence in PWID was reduced from 34%/4.8% in 2015 to 11%/1.4% in 2030. There was little overlap between the two goals: treating mild stage had virtually no impact on ESLD/HCC within 15 years, but the long timescale of liver disease means relatively few PWID reach cirrhosis before cessation of injecting. Strategies focussing on treating advanced disease have the potential for dramatic reductions in severe morbidity, but virtually no preventative impact.
Project description:AIMS:Optimal diabetes care requires clear understanding of the incidence of hypoglycaemia in real-world clinical practice. Current data on hypoglycaemia are generally limited to those reported from randomised controlled clinical trials. The Hypoglycaemia Assessment Tool (HAT) study, a non-interventional real-world study of hypoglycaemia, assessed hypoglycaemia in 27?585 individuals across 24 countries. The present study compared the incidence of hypoglycaemia from the HAT study with other similarly designed, large, real-world studies. MATERIALS AND METHODS:A literature search of PubMed (1995-2017) for population-based studies of insulin-treated patients with type 1 or type 2 diabetes (T1D, T2D), excluding clinical trials and reviews, identified comparable population-based studies reporting the incidence of hypoglycaemia. RESULTS:The 24 comparative studies, including more than 24?000 participants with T1D and more than 160?000 participants with T2D, varied in design, size, inclusion criteria, definitions of hypoglycaemia and method of recording hypoglycaemia. Reported rates (events per patient-year [PPY]) of hypoglycaemia were higher in patients with T1D than in those with T2D (overall T1D, 21.8-73.3 and T2D, 1.3-37.7; mild/non-severe T1D, 29.0-126.7 and T2D, 1.3-41.5; severe T1D, 0.7-5.8 and T2D, 0.0-2.5; nocturnal T1D, 2.6-11.3 and T2D, 0.38-9.7) and were similar to the ranges found in the HAT study. CONCLUSIONS:The HAT data on hypoglycaemia incidence were comparable with those from other real-world studies and indicate a high incidence of hypoglycaemia among insulin-treated patients. Differences in rates among studies are mostly explained by differences in patient populations and study methodology. The goal of reducing hypoglycaemia should be a target for continued educational and evidence-based pharmacological interventions.