The British Diabetic Association Cohort Study, I: all-cause mortality in patients with insulin-treated diabetes mellitus.

AIMS: To assess mortality in patients with diabetes incident under the age of 30 years. METHODS: A cohort of 23 752 diabetic patients diagnosed under the age of 30 years from throughout the United Kingdom was identified during 1972-93 and followed up to February 1997. Following notification of deaths during this period, age- and sex-specific mortality rates, attributable risks and standardized mortality rates were calculated. RESULTS: The 23 752 patients contributed a total of 317 522 person-years of follow-up, an average of 13.4 years per subject. During follow-up 949 deaths occurred in patients between the ages of 1 and 84 years, 566 in males and 383 in females. All-cause mortality rates in the patients with diabetes exceeded those in the general population at all ages and within the cohort were higher for males than females at all ages except between 5 and 15 years. The relative risk of death (standardized mortality ratio, SMR), was higher for females than males at all ages, being 4.0 (95% CI 3.6-4.4) for females and 2.7 (2.5-2.9) for males overall, but reaching a peak of 5.7 (4.7-7.0) in females aged 20-29, and of 4.0 (3.1-5.0) in males aged 40-49. Attributable risks, or the excess deaths in persons with diabetes compared with the general population, increased with age in both sexes. CONCLUSIONS: This is the first study from the UK of young patients diagnosed with diabetes that is large enough to calculate detailed age-specific mortality rates. This study provides a baseline for further studies of mortality and change in mortality within the United Kingdom.     

Massive hemoptysis in cystic fibrosis

BACKGROUND: Massive hemoptysis is a complication commonly reported in patients with cystic fibrosis (CF). An understanding of the pathophysiology of this complication and its consequences is important for the management of patients with CF. OBJECTIVES: To identify risk factors associated with massive hemoptysis, and to determine the prognosis of patients following an episode of massive hemoptysis. DESIGN: A retrospective, observational cohort study of the National CF Patient Registry between the years 1990 to 1999. PATIENTS: The Registry contained data on 28,858 patients with CF observed over 10 years at CF centers across the United States. RESULTS: Massive hemoptysis occurred with an average annual incidence of 0.87% and in 4.1% of patients overall. There was no increased occurrence by sex, but it was more prevalent in older patients (mean age, 24.2 +/- 8.7 years [+/- SD]) with more severe pulmonary impairment (nearly 60% of patients who had an episode of massive hemoptysis had FEV1 < 40% predicted). The principal risks associated with an increased occurrence of massive hemoptysis included the presence of Staphylococcus aureus in sputum cultures (odds ratio [OR], 1.3) and diabetes (OR, 1.1). There was an increased morbidity (eg, increased hospitalizations and hospital days) and an increased 2-year mortality following massive hemoptysis. CONCLUSION: Massive hemoptysis is a serious complication in CF patients, occurring more commonly in older patients with more advanced lung disease. Nearly 1 in 100 patients will have this complication each year. There is an attributable mortality to the complication and considerable morbidity, resulting in increased health-care utilization and a measurable decline in lung function.     

Rapid increase in the incidence of clinically diagnosed type 2 diabetes in Chinese in Harbin between 1999 and 2005

AIM: To examine the recent trend in the incidence of clinically diagnosed type 2 diabetes during the period of 1999-2005 in Harbin, China. METHODS: The records of newly diagnosed type 2 diabetes from hospitals and clinics in Harbin were reported to the Harbin Centre for Disease Control and Prevention. About 3 million (33%) of the total population were from six metropolitan districts and over 6 million (67%) from the surrounding counties. Incidence rates and incidence rate ratios (IRR) were estimated using Poisson regression. RESULTS: During the observational period, 26,953 new cases of diagnosed type 2 diabetes were reported. Among them, 16,367 were from the metropolitan region and 10,586 from the surrounding counties. The incidence rate of type 2 diabetes in the metropolitan region was 3.19 (95% CI: 3.11, 3.27) times as high as that in the surrounding counties. Females had higher incidence rates in younger age groups (<54 years) and lower rates in older age groups (55+ years) than their male counterparts. The incidence increased over time during the period of 1999-2005 by an average of 12% per year (IRR=1.12, 95% CI: 1.11, 1.13). Similar increasing rates were observed in both the county and metropolitan regions. CONCLUSIONS: The incidence of diagnosed type 2 diabetes has increased dramatically in recent years. Although an increasing trend in the incidence of type 2 diabetes exists in both metropolitan and county regions, the county region currently has a substantially lower incidence rate than the metropolitan region.     

Metabolic syndrome and cardiovascular mortality in older type 2 diabetic patients: a longitudinal study

BACKGROUND: Although age does not seem to modify the association of the metabolic syndrome (MS) with cardiovascular risk in middle-aged individuals, no comparison of risks associated with MS between old and middle-aged persons has been reported so far. METHODS: An observational study was performed on a consecutive series of 1716 type 2 diabetic outpatients (age range: 28-96 years). The diagnosis of MS was made following either the National Cholesterol Education Program-Adult Treatment Panel (NCEP-ATPIII) or the International Diabetes Federation (IDF) criteria. RESULTS: The difference in cardiovascular mortality between patients with and without MS was significant up to the age of 70 years. After adjusting for age and sex, hazard ratios of MS for cardiovascular mortality were 3.03 (95% confidence interval, 1.45-6.29), 1.56 (0.91-2.68), and 1.17 (0.42-3.22) in patients < or =70, 71-80, and >80 years old, respectively. CONCLUSIONS: MS is associated with increased cardiovascular risk in middle-aged type 2 diabetic patients, and the clinical utility of this category in older diabetic individuals is questionable.     

Type 2 (non-insulin-dependent) diabetes mellitus and cardiovascular disease — putative association via common antecedents; further evidence from the whitehall study

Summary Fifteen year mortality rates are reported for men participating in the Whitehall Study in 1968–1970. Subjects were divided into four groups — normoglycaemic (centiles 1–95 of the blood glucose distribution: n=17,051), glucose intolerant (centiles 96–100: n = 999), newly diagnosed diabetic patients (n=56) and previously diagnosed diabetic patients (n=121) treated with diet±tablets. Relative risks for all causes mortality and from coronary and cardiovascular disease deaths were calculated. Age adjusted relative risks were highest in the newly diagnosed diabetic patients and were also increased in glucose intolerant and previously diagnosed diabetic men (p<0.05), but did not increase with increasing duration of diabetes. With adjustment for other risk factors, relative risks were similar in newly diagnosed and previously diagnosed diabetic men. There was no significant linear trend of adjusted relative risks with duration of diabetes when all diabetic men were pooled and person years at risk calculated. The lack of effect of duration upon relative risk together with other observations suggests common, possibly genetic, antecedents of both Type 2 (non-insulin-dependent) diabetes and coronary heart disease.     

The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up

BACKGROUND: Epidemiological studies have reported that patients with type 2 diabetes mellitus (DM) have increased mortality and morbidity from cardiovascular diseases, independent of other risk factors. However, most of these studies have been performed in selected patient groups. The purpose of the present study was prospectively to assess the impact of type 2 DM on cardiovascular morbidity and mortality in an unselected population. METHODS: A total of 13,105 subjects from the Copenhagen City Heart Study were followed up prospectively for 20 years. Adjusted relative risks of first, incident, admission for, or death from ischemic heart disease, acute myocardial infarction, or stroke, as well as total mortality in persons with type 2 DM compared with healthy controls, were estimated. RESULTS: The relative risk of first, incident, and admission for myocardial infarction was increased 1.5- to 4.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. The relative risk of first, incident, and admission for stroke was increased 2- to 6.5-fold in women and 1.5- to 2-fold in men, with a significant difference between sexes. In both women and men the relative risk of death was increased 1.5 to 2 times. CONCLUSIONS: In persons with type 2 DM, the risk of having an incident myocardial infarction or stroke is increased 2- to 3-fold and the risk of death is increased 2-fold, independent of other known risk factors for cardiovascular diseases.     

Diabetes,pulse pressure and cardiovascular mortality: the Hoorn Study

OBJECTIVE: Type 2 diabetic patients have an increased arterial stiffness and a very high risk of cardiovascular death. The present study investigated the relationship between pulse pressure, an indicator of vascular stiffness, and risk of cardiovascular mortality among type 2 diabetic and non-diabetic individuals. Second, we determined the relationship between pulse pressure and its main determinant (i.e. age), and the influence of diabetes and mean arterial pressure on this relationship. DESIGN AND METHODS: We studied a cohort of 2484 individuals including 208 type 2 diabetic patients. Mean age and median follow-up for non-diabetic and diabetic individuals, respectively, were 61 and 66 years, and 8.8 and 8.6 years. One-hundred and sixteen non-diabetic and 34 diabetic individuals died of cardiovascular causes. Relative risks of cardiovascular mortality were estimated by Cox proportional hazards regression adjusted for age, gender and mean arterial pressure. RESULTS: Pulse pressure was associated with cardiovascular mortality among the diabetic, but not among the non-diabetic individuals [adjusted relative risk (95% confidence interval) per 10 mmHg increase, 1.27 (1.00-1.61) and 0.98 (0.85-1.13), P interaction = 0.07]. Further adjustment for other risk factors gave similar results. The association, at baseline, between age and pulse pressure was dependent on the presence of diabetes (P interaction = 0.03) and on the mean arterial pressure (P interaction< 0.001) (i.e. there was a stronger association when diabetes was present and when mean arterial pressure was higher). CONCLUSIONS: We conclude that, in type 2 diabetes, pulse pressure is positively associated with cardiovascular mortality. The association between age and pulse pressure is influenced by the presence of type 2 diabetes and by the height of the mean arterial pressure. These findings support the concept of accelerated vascular aging in type 2 diabetes.     

Self-care behaviors of Filipino-American adults with type 2 diabetes mellitus

AimTo examine the diabetes self-care behaviors of Filipino-American (FA) adults with type 2 diabetes mellitus (DM).MethodThe Summary of Diabetes Self Care Activities–Revised and Expanded measure was administered to 192 (74 males and 118 females) FA adult immigrants with type 2 DM.ResultsOlder FAs (≥65 years), females, those who were older when they immigrated, and participants diagnosed with type 2 DM longer were more likely to follow recommended medication regimens. Younger FAs (<65 years) and participants diagnosed with type 2 DM for shorter duration of time were less likely to perform blood glucose testing. Most FAs reported following their eating plans; however, those who lived in the United States (US) longer followed healthful eating plans. Likewise, females reported eating five or more servings of fruits and/or vegetables daily. Moreover, older FAs reported evenly spacing carbohydrate intake everyday. Furthermore, older participants, those with less education, participants who were older when they immigrated, and those older when diagnosed with type 2 DM ate fewer foods high in fats. As to physical activity, FA males and participants with higher education exercised more frequently.ConclusionYounger FAs were less likely to perform optimum type 2 DM self-care behaviors pertaining to diet, medication taking, and blood glucose testing compared to their older counterparts. This finding suggests an increased risk for type 2 DM comorbidities and/or complications in younger FAs, which may require more intensive treatments in later years.     

Systematic review and meta-analysis of age at menarche and risk of type 2 diabetes

The relation of early menarche with type 2 diabetes mellitus (T2DM) remains inconsistent across studies. The objective of this systematic review and meta-analysis of published population-based observational studies was to assess the association between age at menarche and T2DM risk. We searched online data bases through December 2013 and examined the reference lists of pertinent articles. Summary relative risks (RRs) with 95 % confidence intervals (CIs) were calculated with a random-effects model. A total of 14 effect estimates from 10 eligible studies (three cross-sectional and seven cohort studies) included 315,428 participants and 22,085 cases of T2DM. Compared with the highest or middle category, women in the lowest category of age at menarche had higher risk of T2DM [summary RR (95 % CI) 1.22 (1.17, 1.28)]. These results were consistent between studies that conducted in the United States and in Europe. The association between age at menarche and T2DM was slightly stronger for cohort than for cross-sectional studies. These findings strongly support an association between younger age at menarche and increased risk of T2DM. Age at menarche may help identify women with increased risk of developing T2DM.     

Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men.

BACKGROUND: Television (TV) watching, a major sedentary behavior in the United States, has been associated with obesity. We hypothesized that prolonged TV watching may increase risk for type 2 diabetes. METHODS: In 1986, 37 918 men aged 40 to 75 years and free of diabetes, cardiovascular disease, and cancer completed a detailed physical activity questionnaire. Starting from 1988, participants reported their average weekly time spent watching TV on biennial questionnaires. RESULTS: A total of 1058 cases of type 2 diabetes were diagnosed during 10 years (347 040 person-years) of follow-up. After adjustment for age, smoking, alcohol use, and other covariates, the relative risks (RRs) for type 2 diabetes across increasing quintiles of metabolic equivalent hours (MET-hours) per week were 1.00, 0.78, 0.65, 0.58, and 0.51 (P for trend, <.001). Time spent watching TV was significantly associated with higher risk for diabetes. After adjustment for age, smoking, physical activity levels, and other covariates, the RRs of diabetes across categories of average hours spent watching TV per week (0-1, 2-10, 11-20, 21-40, and >40) were 1.00, 1.66, 1.64, 2.16, and 2.87, respectively (P for trend, <.001). This association was somewhat attenuated after adjustment for body mass index, but a significant positive gradient persisted (RR comparing extreme categories, 2.31; P for trend,.01). CONCLUSIONS: Increasing physical activity is associated with a significant reduction in risk for diabetes, whereas a sedentary lifestyle indicated by prolonged TV watching is directly related to risk. Our findings suggest the importance of reducing sedentary behavior in the prevention of type 2 diabetes.     

Obesity, bariatric surgery and type 2 diabetes--a systematic review

Obesity is endemic in the United States and is closely linked to the development of type 2 diabetes. Both obesity and diabetes are responsible for significant morbidity and mortality. Likewise, both conditions are resistant to treatment. Recent studies have evaluated prevention of type 2 diabetes through intensive lifestyle intervention, while others are examining the impact of bariatric surgery on type 2 diabetes. This article presents an overview of the impact of bariatric surgical and lifestyle interventions on the prevention and treatment of type 2 diabetes. Although studies using a variety of bariatric surgical techniques are included, the focus is on two interventions in particular: the Roux-en-Y gastric bypass and the laparoscopic silicone gastric banding procedure. Outcomes of these procedures are further contrasted with recent lifestyle intervention studies, in particular, the Diabetes Prevention Program study. Gastric bypass studies have been associated with a 99 to 100% prevention of diabetes in patients with IGT and an 80 to 90% clinical resolution of diagnosed early type 2 diabetes. Gastric banding procedures are associated with a lower median (50-60%) clinical remission of type 2 diabetes. Lifestyle intervention studies of obese and glucose-intolerant patients have achieved a 50% reduction in the progression of IGT to diabetes over the short term, with no reported resolution of the disease. Weight loss by any means in the obese patient appears to prevent progression to type 2 diabetes, at least in the short term. Furthermore, sustained weight loss through bariatric surgical intervention is associated both with prevention of progression of IGT and with clinical remission of early type 2 diabetes.     

The influence of age on the effects of lifestyle modification and metformin in prevention of diabetes

BACKGROUND: The incidence of type 2 diabetes increases with age. It is unknown whether interventions to prevent diabetes are as effective in elderly persons as in younger adults. METHODS: The Diabetes Prevention Program (DPP) demonstrated that an intensive lifestyle intervention (ILS) or metformin could prevent or delay diabetes. A predefined secondary outcome of DPP was to determine if treatment effects varied by age. RESULTS: At baseline, participants aged 60-85 years were leaner and had the best insulin sensitivity and lowest insulin secretion compared to younger age groups. Diabetes incidence rates did not differ by age in the placebo group, but ILS was more effective with increasing age (6.3, 4.9, and 3.3 cases per 100 person-years, in the 25-44, 45-59, and 60-85 year age groups, respectively; p(trend) =.007). Participants aged 60-85 years had the most weight loss and metabolic equivalent (MET)-hours of physical activity. The metformin group showed a trend toward higher diabetes incidence among older participants (6.7, 7.7, and 9.3 cases per 100 person-years in the 25-44, 45-59, and 60-85 year age groups, respectively; p(trend) =.07); and diabetes risk increased with age (hazard ratio [age 60-85 vs 25-44] 1.63, p =.02), after adjusting for the greater weight loss in the 60-85 year age group. CONCLUSIONS: Lifestyle modification was exceptionally effective in preventing diabetes in older individuals; this finding was largely explained by greater weight loss and physical activity. The limited effectiveness of metformin in older persons may reflect age-related differences in insulin action and secretion. A lifestyle modification program can be recommended for older individuals at high risk for type 2 diabetes.     

The growing burden of diabetes mellitus in the US elderly population

BACKGROUND: The prevalence of diabetes mellitus is growing worldwide. Consequently, there has been increased emphasis on primary and secondary prevention of diabetes. To our knowledge, whether there have been actual improvements in outcomes in the last decade or so has not been documented in a nationally representative sample. METHODS: We undertook this study to examine trends in rates of occurrence of diabetes and its complications in persons older than 65 years in the United States. National longitudinal analysis of Medicare claims and other Medicare program data for persons first diagnosed as having diabetes during 1994 (n=33 164), 1999 (n=31 722), or 2003 (n=40 058) were compared with 2 control groups of persons of approximately equal sample size who were not diagnosed as having diabetes, alternatively during 1994, 1999, or 2003 or for the entire period from 1994 to 1999 or from 1999 to 2004. The main outcome measures were death and complications of diabetes including cardiovascular, cerebrovascular, ophthalmic, renal, and lower extremity events. RESULTS: The annual incidence of diabetes increased by 23% between 1994-1995 and 2003-2004, and prevalence increased by 62%. The mortality rate after diagnosis in persons having diagnosed diabetes decreased by 8.3% compared with that in the control groups. Complication rates among persons diagnosed as having diabetes generally increased or stayed the same compared with those in the control groups during 1994 to 2004 except for ophthalmic diseases associated with diabetes. Rates for some major complications were high; for example, the rate for congestive heart failure in the diabetes group during 1999 to 2004 was 475 per 1000 persons. In some cases, most notably renal events, including the most serious complications, there were increases in prevalence in both the diabetes and control groups. CONCLUSION: The burden of financing and providing medical care for persons older than 65 in the United States having diagnosed diabetes is growing rapidly as a result of increased incidence and, especially, prevalence of diagnosed diabetes, decreased mortality, and overall lack of improvement in rates of complications in persons having diagnosed diabetes.     

The British Diabetic Association Cohort Study, II: cause-specific mortality in patients with insulin-treated diabetes mellitus.

AIMS: To measure cause-specific mortality, by age, in patients with insulin-treated diabetes incident at a young age. METHODS: A cohort of 23 752 patients with insulin-treated diabetes diagnosed under the age of 30 years, from throughout the United Kingdom, was identified during 1972-93 and followed to February 1997. Death certificates have been obtained for deaths during the follow-up period and cause-specific mortality rates and standardized mortality ratios by age and sex are reported. RESULTS: During the follow-up period 949 deaths occurred and at all ages mortality rates were considerably higher than in the general population. Acute metabolic complications of diabetes were the greatest single cause of excess death under the age of 30 years. Cardiovascular disease was responsible for the greatest proportion of the deaths from the age of 30 years onwards. CONCLUSIONS: Deaths in patients with diabetes diagnosed under the age of 30 have been reported and comparisons drawn with mortality in the general population. To reduce these deaths attention must be paid both to the prevention of acute metabolic deaths and the early detection and treatment of cardiovascular disease and associated risk factors.     

Impaired glucose tolerance predicts all-cause mortality among older men at high risk for cardiovascular disease in China

AimsTo investigate the potential association between impaired glucose tolerance (IGT) and all-cause mortality among older men at high risk for cardiovascular disease (CVD) in China.MethodsIn this prospective observational study, 460 older men aged ≥60 years were determined to have either IGT or normal glucose tolerance (NGT) based on an oral glucose tolerance test conducted between May 2005 and May 2007. IGT and NGT were diagnosed according to the 1999 WHO diagnostic criteria. All subjects were followed until March 2017. The primary outcome studied was all-cause mortality. Multivariate Cox models were used to estimate relative risk for all-cause mortality.ResultsDuring a mean follow-up of 11.2 years, forty-three (21.4%) subjects in the IGT group and twenty-nine (11.2%) subjects in the NGT group died (HR 2.05, 95% CI 1.28–3.28, P = 0.003). Multivariate Cox proportional-hazards analysis demonstated that IGT was significantly associated with increased risk for all-cause mortality, composite cardiovascular outcome, nonfatal stroke and heart failure after adjusting for potential confounding factors. Logistic regression analysis showed that IGT at baseline (P < 0.05) rather than incident type 2 diabetes was a risk factor of all-cause mortality.ConclusionsIGT was significantly associated with all-cause mortality in older Chinese men at high risk for CVD.     

Evaluation of adverse outcome in young women with polycystic ovary syndrome versus matched, reference controls: a retrospective, observational study

Context: Polycystic ovary syndrome (PCOS) is associated with insulin resistance, hyperandrogenism, and dyslipidemia, but the effects of these disturbances on long-term health are not fully understood. Aim: Our aim was to determine the relative risk of type 2 diabetes, cancer, large-vessel disease (LVD), and all-cause mortality for women diagnosed with PCOS. Design: Data were extracted from the General Practice Research Database, a longitudinal, anonymized research database derived from nearly 600 primary-care practices in the United Kingdom. Patients with a diagnosis of PCOS between 1990 and 2010 were selected. Patients were matched to two sets of controls. The first set was matched according to primary-care practice and age, and the second was also matched on body mass index. Primary outcome was first incident record of diabetes. Crude rates for diabetes were presented, and time to diabetes was analyzed using Cox proportional hazard models. Secondary outcomes (cancer, LVD, and mortality) were also modeled. Results: Of 53,303 identified with a diagnosis of PCOS, 21,740 (40.8%) met the eligibility criteria. Median follow-up was 4.7 yr (interquartile range = 2.0-8.6 yr) in those with PCOS and 5.8 yr (2.7-9.6) in the reference group. Crude rates of diabetes were 5.7 and 1.7 per 1000 patient-years for cases and controls, respectively. The corresponding adjusted hazard ratio was 3.015 (95% confidence interval = 2.733-3.327). Of cases matched by body mass index, crude rates of diabetes were 4.7 and 2.4 per 1000 patient-years, respectively. The corresponding adjusted hazard ratio was 1.752 (1.514-2.028). No significant difference in BMI-adjusted risk was evident for cancer, LVD, or all-cause mortality. Conclusions: During this follow-up period, women with PCOS were not at increased risk of LVD, cancer, or death, but they had increased risk of type 2 diabetes.     

Blood pressure, smoking and body mass in relation to mortality from stroke and coronary heart disease in the elderly. A 10-year follow-up in Norway.

OBJECTIVES: To examine the association between blood pressure, smoking and body mass index (BMI) and cerebro- and cardiovascular mortality in a population of healthy elderly. DESIGN: Ten-year mortality follow-up of elderly men and women who participated in the Nord-Tr?ndelag Health Study 1984-86. SETTING: Nord-Tr?ndelag county, Norway. SUBJECTS: 3121 men and 3271 women aged 70 years and older, free from any diagnosed atherosclerotic diseases or diabetes at baseline. MAIN OUTCOME MEASURES: Relative risk of cerebro- and cardiovascular mortality and all-cause mortality according to blood pressure, smoking and BMI. RESULTS: There was a consistent, positive association between systolic and diastolic blood pressure and cerebro- and cardiovascular mortality. The association persisted after adjustment for potential confounding factors, and was strongest for cerebrovascular mortality; the adjusted relative risks for systolic blood pressure categories 160-179 mmHg and > or = 180 mmHg in men were 1.63 (95% confidence interval, CI 1.06-2.53) and 2.19 (95% CI 1.39-3.44) compared to blood pressure < 140 mmHg. In women, the corresponding relative risks were 1.54 (95% CI 0.93-2.56) and 2.12 (95% CI 1.29-3.50). For diastolic blood pressure the adjusted relative risks in categories 100-109 and > or = 110 mmHg in men were 1.88 (95% CI 1.19-2.95) and 3.06 (95% CI 1.79-5.21) compared to pressure <90 mmHg. The corresponding relative risks in women were 1.75 (95% CI 1.05-2.91) and 2.02 (95% CI 1.04-3.93). Current smoking increased cardiovascular mortality in both men and women, and among women, BMI was negatively associated with all-cause mortality. CONCLUSIONS: These findings add to the growing evidence that hypertension is a major risk factor for mortality from stroke and coronary heart disease among the elderly and the very old.     

Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing

Background

Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project.

Methods

Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention.

Results

Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c <8.5% because of scarce data on clinically relevant benefits of their use. Twenty-two of the included studies were funded by pharmaceutical companies and authored or co-authored by employees of the sponsor.

Conclusions

Other than the surrogate endpoint of improved glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4 inhibitors might have a lower risk of hypoglycaemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed that evaluate the risks and benefits of DPP-4 inhibitors for the management of type 2 diabetes mellitus in older adults, using clinically relevant outcomes and including representative samples of older adults with information on their frailty status and comorbidities. Studies are also needed that are independent of pharmaceutical company involvement.

     

Alcohol use, comorbidity, and mortality

OBJECTIVES: To examine the combined influence of alcohol use and comorbidity on 20-year mortality in older adults (average age 66 at the time of the baseline survey). DESIGN: Longitudinal analysis of a national probability sample-based cohort study. SETTING: Data sources were the National Health and Nutrition Examination Survey I (NHANES I), 1971-1974, and the NHANES Epidemiologic Followup Survey, 1992. PARTICIPANTS: Four thousand six hundred ninety-one adults aged 60 and older who provided data on alcohol use. MEASUREMENTS: The prevalence of at-risk drinking in older adults in the United States and the 20-year all-cause mortality risk associated with it. At-risk drinking status was determined from amount of alcohol consumed and comorbidities, using a previously validated method. RESULTS: The prevalence of at-risk drinking in the United States between 1971 and 1974 in older adults was 10% (18% of men, 5% of women). The majority of at-risk drinkers were identified as such because of their use of alcohol in amounts deemed risky in the presence of relevant comorbidities (69%) (e.g., drinking 2-3 drinks per day and having gout or anxiety or taking a medication for pain). In men, at-risk drinking was associated with higher mortality rates than not-at-risk drinking (hazard ratio=1.20, 95% confidence interval=1.01-1.41); abstinence was not associated with greater mortality. In women, neither abstinence nor at-risk drinking was associated with greater mortality rates. CONCLUSION: In this first, large population-based study of older adults examining the mortality risks of alcohol use and comorbidity, at-risk drinking was associated with greater mortality rates in men. These findings suggest that a lower threshold of alcohol use should be recommended for older adults with specific comorbidities to reduce mortality risks.     

Hospitalization for pneumonia in the Cardiovascular Health Study: incidence, mortality, and influence on longer-term survival

OBJECTIVES: To estimate the rate of hospitalization for pneumonia in community-dwelling older adults and to assess its risk factors and contribution to mortality. DESIGN: Prospective observational study. SETTING: The Cardiovascular Health Study (CHS) in four U.S. communities. PARTICIPANTS: Five thousand eight hundred eighty-eight men and women aged 65 and older who were followed for a median 10.7 years. MEASUREMENTS: Participants were interviewed about medical history and demographics; evaluated for lung, physical, and cognitive function; and followed for hospitalizations, cardiovascular disease, and death. RESULTS: Nearly 10% of the cohort was hospitalized for pneumonia, for a rate of 11.1 per 1,000 person-years (95% confidence interval (CI)=10.2-12.0). Risk factors included older age, male sex, current and past smoking, poor physical and lung function, and history of cardiovascular disease and chronic obstructive pulmonary disease. Ten percent of participants died during their incident pneumonia hospitalization, and death rates were high in those who survived to discharge. Compared with participants who had not been hospitalized for pneumonia, the relative risk of total mortality was 4.9 (95% CI=4.1-6.0) during the first year after hospitalization and 2.6 (95% CI=2.2-3.1) thereafter, adjusted for age, sex, and race. The respective relative risks were 3.9 (95% CI=3.1-4.8) and 2.0 (95% CI=1.6-2.4) after further adjustment for baseline history of cardiovascular disease; diabetes mellitus; smoking; and measures of lung, physical, and cognitive function. CONCLUSION: In older people, hospitalization for pneumonia is common and is associated with an elevated risk of death, as shown in this population-based, prospective cohort.