Diabetes Hazard Ratio Research Articles

Association between hydroxychloroquine use and risk of diabetes mellitus in systemic lupus erythematosus and rheumatoid arthritis: a UK Biobank-based study

Context/ObjectivesHydroxychoroquine has hypoglycemic effects and may reduce the risk of diabetes mellitus (DM). We determined the association between hydroxychoroquine use and the incidence of DM in a population-based cohort of pations with Rheumatic diseaseMethodsA prospective cohort study among 502392 Potentially eligible participants in the context of UK Biobank, recruitment to the database began between 2006 and 2010. Patients diagnosed with diabetes and fasting glucose greater than or equal to 7 mmol/L at baseline (n=619) were excluded and patients diagnosed with either RA or SLE at baseline (n=6793) were followed up until 2022. Diagnosis was recorded using the International Classification of Diseases, tenth edition (ICD-10) code. The mean follow-up was 13.78 years and the primary outcome was newly recorded type 2 diabetes mellitus (T2DM), with the time of onset of diabetes as the follow-up endpoint date.ResultsDuring a median follow-up period of 13.78 (12.93, 14.49) years, diabetes developed in 537 participants, with an incidence of 7.9%. New diabetes cases not taking hydroxychloroquine and taking hydroxychloroquine was 504 (8.03%) and 33 (6.36%), respectively. In univariate models, the hazard ratio for diabetes was 0.89 (95% confidence interval, 0.81-0.98, P=0.014) for hydroxychloroquine users compared with those not taking hydroxychloroquine. After adjusting for age, sex, race, education level, and BMI the hazard ratio for incident diabetes among hydroxychloroquine users was 0.88 (95% confidence interval, 0.80-0.97, P=0.008). In complete multivariate model hazard ratio for hydroxychloroquine was 0.87 (95% confidence interval, 0.79- 0.96, P=0.005).ConclusionHydroxychloroquine was associated with decreased risk of DM among rheumatoid arthritis patients, our data taken together with correlational studies, warrant further investigation of the potential preventive effect of hydroxychloroquine against T2DM.

353. New-Onset Diabetes as an Acute Complication of COVID-19: A National Population Cohort Analysis

BackgroundDiabetes is emerging as one of the complications of coronavirus disease 2019 (COVID-19), but this is hard to be revealed with cross-sectional studies since it is also known as the major predisposing factor for high-risk COVID-19. Therefore, this study aimed to estimate the risk of new-onset diabetes after COVID-19 through a population follow-up study.MethodsAll COVID-19 confirmed cases in Korea from January 20 to June 4, 2020, were matched with national health insurance data and their health screening data, both provided by the National Health Insurance Service of Korea. Controls were selected as the people who received the PCR test for COVID-19 and showed negative results in the same period and followed up until July 19, 2020. We selected the outcome as the diagnosis of diabetes according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10, E10 – E14). People who were diagnosed with diabetes in the past five years were excluded from both groups. After performing a log-rank test between groups, adjusted incidence rate and hazard ratio were estimated using Cox proportional hazard modeling. Demographic characteristics (age, sex, region, family histories of hypertension/diabetes, and income) and underlying health conditions such as hypertension, dyslipidemia, heart disease, alcohol consumption, cigarette smoking, and BMI were adjusted. Proportional assumptions were tested by the zph test and the sensitivity analysis by excluding each factor in turn and comparing results.ResultsA total of 6,247 COVID-19 patients and 143,594 controls without diabetes in the past were included for the analysis. The number of new-onset diabetes were 759 (12.15%) in COVID-19 patients and 3,465 (2.41%) in controls (P < 0.01). The adjusted incidence of diabetes was 15.34 (95% confidence interval, CI: 14.10 – 16.66) and 11.18 (95% CI: 10.67 – 11.72) per 100 person-year, respectively, with the mean follow-up time as 46.31 (standard deviation: 16.37) days. The adjusted hazard ratio of diabetes in COVID-19 cases was 2.97 (95% CI: 2.44 – 3.63).ConclusionSince COVID-19 patients showed a higher incidence of new-onset diabetes in a short-time follow-up, we should consider diabetes as one of the possible complications of COVID-19. Disclosures All Authors: No reported disclosures

Polycystic ovary syndrome is a risk factor for diabetes and prediabetes in middle-aged but not elderly women: a long-term population-based follow-up study

To study the incidence rate and hazard ratios of diabetes and prediabetes between women with PCOS and healthy subjects. Prospective population-based study. Not applicable. Women with PCOS (n = 178) and eumenorrheic, nonhirsute, healthy women as controls (n = 1,524), all followed for a median time of 12.9years. None. Incidence rate and hazard ratios of diabetes and prediabetes between women with PCOS and healthy controls. We analyzed the participants on two pathways. First, for detecting new diabetes mellitus (DM) events, we selected participants who were free of DM at baseline (n = 39). Second, for detecting new pre-DM events, we selected participants who were free of pre-DM and DM at baseline (n = 222) from the baseline population. The rest of the population were included for final analysis to calculate the incidence rates and hazard ratio of diabetes and prediabetes events. The incidence rates of diabetes were 12.9 and 4.9 per 1,000 person-years for PCOS and controls, respectively. This incidence rate in women younger than 40 with and without PCOS was 13.4 and 4.2, respectively. The adjusted hazard ratio (HR) for women ≤40 was 4.9 (95% confidence interval [CI], 2.5-9.3). There were no statistically significant differences between the two groups studied after age 40. The incidence rates of prediabetes were 29.7 and 25.9 per 1,000 person-years for PCOS and healthy women, respectively. The incidence rate in women younger than 40 with and without PCOS was 30.3 and 23.9, respectively. The adjusted HR for women ≤40years, 1.7 (95% CI, 1.1-2.6), disappeared after age40. These data suggest that routine screening for diabetes in prevention strategies does not need to be emphasized for PCOS patients at late reproductive ages if they have not been affected by glucose intolerance up to that point.

Arterial Stiffness and Incidence of Diabetes: A Population-Based Cohort Study.

Diabetes is known to be associated with increased arterial stiffness. However, the temporal association between increased carotid-femoral pulse wave velocity (c-f PWV) and diabetes is unclear. The aim of this study is to explore the relationship between arterial stiffness, as determined by c-f PWV, and incidence of diabetes. The study population included participants from the Malmö Diet and Cancer cardiovascular cohort, using measurements from the 2007-2012 reexamination as baseline. Arterial stiffness was evaluated by measuring c-f PWV (SphygmoCor). After excluding participants with prevalent diabetes (according to measurements of fasting glucose, oral glucose tolerance tests, and physician's diagnoses), the final study population consisted of 2,450 individuals (mean age = 71.9 ± 5.6 years). Incidence of diabetes was followed by linkage to local and national diabetes registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to the tertiles of c-f PWV, adjusted for potential confounders. During a mean follow-up of 4.43 ± 1.40 years, 68 (2.8%) participants developed diabetes. Crude incidence of diabetes (per 1,000 person-years) was 3.5, 5.7, and 9.5, respectively, for subjects in the first, second, and third tertiles of c-f PWV. After adjustment for potential confounders, the hazard ratio of diabetes was 1.00 (reference), 1.83 (95% CI 0.88-3.8), and 3.24 (95% CI 1.51-6.97), respectively, for the tertiles of c-f PWV (P for trend = 0.002). Increased c-f PWV is associated with increased incidence of diabetes, independent of other risk factors. These results suggest that increased arterial stiffness is an early risk marker for developing diabetes.

Group-Based Trajectory of Body Shape From Ages 5 to 55 Years and Cardiometabolic Disease Risk in 2 US Cohorts.

The association of adiposity across the life span with cardiometabolic risk is not completely delineated. We used a group-based modeling approach to identify distinct trajectories of body shape from ages 5 years to 55 years among 84,792 women from the Nurses' Health Study (1976-2010) and 37,706 men from the Health Professionals Follow-up Study (1986-2010) and assessed the associations between these trajectories and incidence of type 2 diabetes and cardiovascular disease (CVD) during a 17-year follow-up period. Compared with those who maintained leanness throughout the life span ("lean-stable" trajectory), participants who maintained a medium body shape ("medium-stable" trajectory) had somewhat increased risk. Those who started lean but had a moderate or marked increase in adiposity ("lean-moderate increase" and "lean-marked increase" trajectories) had even higher risk (e.g., for a "lean-marked increase" trajectory, the hazard ratio for diabetes was 8.11 (95% confidence interval (95% CI): 7.10, 9.27) in women and 2.36 (95% CI: 2.04, 2.74) in men; for CVD, it was 1.38 (95% CI: 1.25, 1.52) in women and 1.28 (95% CI: 1.16, 1.41) in men). Participants who started heavy and became heavier (a "heavy-increase" trajectory) had substantially elevated risk (for diabetes, the hazard ratio was 7.34 (95% CI: 6.40, 8.42) in women and 2.80 (95% CI: 2.37, 3.31) in men; for CVD, it was 1.55 (95% CI: 1.40, 1.71) in women and 1.35 (95% CI: 1.20, 1.53) in men). Our data showed that trajectories of body shape from ages 5 to 55 years were associated with subsequent risk of developing type 2 diabetes and CVD.

Risk of Diabetes in Older Adults with Co-Occurring Depressive Symptoms and Cardiometabolic Abnormalities: Prospective Analysis from the English Longitudinal Study of Ageing.

High depressive symptoms and cardiometabolic abnormalities are independently associated with an increased risk of diabetes. The purpose of this study was to assess the association of co-occurring depressive symptoms and cardiometabolic abnormalities on risk of diabetes in a representative sample of the English population aged 50 years and older. Data were from the English Longitudinal Study of Ageing. The sample comprised of 4454 participants without diabetes at baseline. High depressive symptoms were based on a score of 4 or more on the 8-item binary Centre for Epidemiologic Studies–Depression scale. Cardiometabolic abnormalities were defined as 3 or more cardiometabolic risk factors (hypertension, impaired glycemic control, systemic inflammation, low high-density lipoprotein cholesterol, high triglycerides, and central obesity). Cox proportional hazards regressions assessed the association between co-occurring depressive symptoms and cardiometabolic abnormalities with incidence of diabetes. Multiple imputation by chained equations was performed to account for missing data. Covariates included age, sex, education, income, smoking status, physical activity, alcohol consumption, and cardiovascular comorbidity. The follow-up period consisted of 106 months, during which 193 participants reported a diagnosis of diabetes. Diabetes incidence rates were compared across the following four groups: 1) no or low depressive symptoms and no cardiometabolic abnormalities (reference group, n = 2717); 2) high depressive symptoms only (n = 338); 3) cardiometabolic abnormalities only (n = 1180); and 4) high depressive symptoms and cardiometabolic abnormalities (n = 219). Compared to the reference group, the hazard ratio for diabetes was 1.29 (95% CI 0.63, 2.64) for those with high depressive symptoms only, 3.88 (95% CI 2.77, 5.44) for those with cardiometabolic abnormalities only, and 5.56 (95% CI 3.45, 8.94) for those with both high depressive symptoms and cardiometabolic abnormalities, after adjusting for socio-demographic, lifestyle and clinical variables. These findings suggest that those with high depressive symptoms and cardiometabolic abnormalities are at a particularly increased risk of type 2 diabetes.

Incidental risk for diabetes according to serum ferritin concentration in Korean men

BackgroundDespite accumulating evidence suggesting the clinical association between serum ferritin concentrations and diabetes, it is not clearly identified in other ethnic groups besides western population. This study analyzed a longitudinal relationship between serum ferritin concentration and the risk for diabetes in non-diabetic Korean men. MethodsThis study was composed of a cohort of 30,002 non-diabetic Korean men who participated in medical health check-up program in 2005. They were divided into 4 groups according to their baseline ferritin concentrations (first quartile–fourth quartile) and monitored until 2010. Their incidences and hazard ratios of diabetes were compared among 4 groups according to their baseline ferritin concentrations. ResultsWhile 2655 cases of diabetes newly developed during follow-up, incidence of diabetes increased proportionally to the baseline serum ferritin concentrations. In Cox-proportional hazard model, hazard ratios for diabetes also independently increased according to the baseline serum ferritin concentrations [quartile 1: 1.00 (reference), quartile 2: 1.00 (0.87–1.12), quartile 3: 1.13 (1.00–1.29), quartile 4: 1.18 (1.04–1.34), respectively]. ConclusionsIncreased ferritin concentration was associated with increased risk for diabetes in Korean men. These findings suggest the clinical significance of serum ferritin concentration in the development diabetes.

C-reactive protein, depressive symptoms, and risk of diabetes: Results from the English Longitudinal Study of Ageing (ELSA)

ObjectivesRaised levels of C-reactive protein (CRP), an inflammatory biomarker, and depressive symptoms are both independently linked to risk of diabetes. The purpose of this study was to assess the joint association of CRP and depressive symptomatology with diabetes incidence in a representative sample of English people ≥50years old. MethodData were from the English Longitudinal Study of Ageing, a prospective study of community-dwelling older adults. The sample was comprised of 4955 participants without self-reported doctor-diagnosed diabetes at baseline. High CRP level was dichotomized as >3mg/L. Elevated depressive symptomatology was defined as ≥4 using the 8-item Center for Epidemiologic Studies Depression Scale. Incident diabetes was determined based on newly self-reported doctor-diagnosed diabetes. Cox proportional hazard regressions were used to examine the association between CRP and depressive symptoms with incidence of type 2 diabetes. ResultsDuring approximately 63.2months of follow-up, 194 participants reported diabetes diagnosis. After adjustment for socio-demographics, lifestyle behaviors, clinical factors, and BMI, the hazard ratio for diabetes was 1.63 (95% CI 0.88–3.01) for people with elevated depressive symptoms only, 1.43 (95% CI 0.99–2.07) for people with high CRP only, and 2.03 (95% CI 1.14–3.61) for people with both high CRP and elevated depressive symptoms. ConclusionThe presence of both high CRP levels and elevated depressive symptoms was associated with risk of diabetes. Further investigation into this relationship could aid in understanding the mechanisms underlying inflammation, depression, and diabetes.

Splenectomy in trauma patients is associated with an increased risk of postoperative type II diabetes: a nationwide population-based study

BackgroundAnimal studies indicate that splenocytes may act as precursors of β-islet secretory cells in the pancreas. This study aimed to assess the risk of postoperative type II diabetes after splenectomy in trauma patients. MethodsWe used data from the Taiwan National Health Insurance hospitalized claims. Study 1 included 3,723 patients receiving splenectomy and 3,723 matched patients receiving other types of abdominal surgery. Study 2 included 5,996 patients with spleen injury and 5,996 matched patients with other types of abdominal injury. The hazard ratio for diabetes was estimated using the matched Cox proportional hazard regression model. ResultsIn trauma patients after surgery, those who received splenectomy had a 2-fold higher risk of diabetes compared with patients without splenectomy after a 3-year follow-up period. In the nonoperative group, there was no difference in diabetes risk between patients with splenic injury and those with other types of injury. ConclusionsSplenectomy was associated with an increased risk of postoperative type II diabetes in trauma patients. Thus, there may be a role for the spleen in the development of diabetes.

Functional Cardiopulmonary Exercise Testing in Potential Renal Transplant Recipients

Functional Cardiopulmonary Exercise Testing in Potential Renal Transplant Recipients

Prevalence of metabolically healthy obesity and its impacts on incidences of hypertension, diabetes and the metabolic syndrome in Taiwan.

Obesity is an epidemic health problem related to morbidity and mortality of metabolic and cardiovascular diseases. However, little is known regarding the development of cardiometabolic diseases in an obese subgroup with a healthy metabolic risk profile. This study examined the prevalence of baseline metabolically healthy obese subjects and its impacts on the incidences of cardiometabolic diseases using a nation-wide population cohort. Metabolically healthy obese were prevalent in 8.2% of the baseline population and 28.5% of the obese subjects. Subjects included were 1,547 men and women (age range, 18-59 years), who were free of components of the metabolic syndrome except waist criteria. During an average 5.4-year follow-up, the cumulative incidences of hypertension, type 2 diabetes and the metabolic syndrome were 7.8%, 1.2% and 5.6%, respectively. The hazard ratios (95% CIs) for the metabolic syndrome incidence were significantly higher at BMI levels of >=23.0 kg/m² [4.68 (2.22-9.86)] for BMI of 23-24.9 kg/m²; 8.82 (4.01-19.4) for BMI of 25-26.9 kg/m²; and 24.43 (12.33-48.41) for BMI of >=27 kg/m²). The hazard ratios for diabetes or hypertension incidence were significantly higher at BMI levels of >=25.0 kg/m2. Each kg/m² of BMI gained was associated with an 18% increase in the risk of developing hypertension and a 26% increase in risk for the metabolic syndrome. We conclude that metabolically healthy obese individuals are at higher risk to develop hypertension, type 2 diabetes and the metabolic syndrome than their non-obese counterparts. Our data provide further evidence that opposes the notion of metabolically healthy obese as harmless conditions.

Smoking, Smoking Cessation, and Risk for Type 2 Diabetes Mellitus

Cigarette smoking is an established predictor of incident type 2 diabetes mellitus, but the effects of smoking cessation on diabetes risk are unknown. To test the hypothesis that smoking cessation increases diabetes risk in the short term, possibly owing to cessation-related weight gain. Prospective cohort study. The ARIC (Atherosclerosis Risk in Communities) Study. 10,892 middle-aged adults who initially did not have diabetes in 1987 to 1989. Smoking was assessed by interview at baseline and at subsequent follow-up. Incident diabetes was ascertained by fasting glucose assays through 1998 and self-report of physician diagnosis or use of diabetes medications through 2004. During 9 years of follow-up, 1254 adults developed type 2 diabetes. Compared with adults who never smoked, the adjusted hazard ratio of incident diabetes in the highest tertile of pack-years was 1.42 (95% CI, 1.20 to 1.67). In the first 3 years of follow-up, 380 adults quit smoking. After adjustment for age, race, sex, education, adiposity, physical activity, lipid levels, blood pressure, and ARIC Study center, compared with adults who never smoked, the hazard ratios of diabetes among former smokers, new quitters, and continuing smokers were 1.22 (CI, 0.99 to 1.50), 1.73 (CI, 1.19 to 2.53), and 1.31 (CI, 1.04 to 1.65), respectively. Further adjustment for weight change and leukocyte count attenuated these risks substantially. In an analysis of long-term risk after quitting, the highest risk occurred in the first 3 years (hazard ratio, 1.91 [CI, 1.19 to 3.05]), then gradually decreased to 0 at 12 years. Residual confounding is possible even with meticulous adjustment for established diabetes risk factors. Cigarette smoking predicts incident type 2 diabetes, but smoking cessation leads to higher short-term risk. For smokers at risk for diabetes, smoking cessation should be coupled with strategies for diabetes prevention and early detection.

Are measures of height and leg length related to incident diabetes mellitus? The ARIC (Atherosclerosis Risk in Communities) study

This study was designed to estimate the risk of developing diabetes in relation to adult height components, namely leg length and leg length/height ratio. Data on 12,800 individuals without diabetes were obtained at the baseline examination from the ARIC cohort. Cox proportional hazard models were used to estimate hazard rate ratios of diabetes for each 5-cm difference in leg length and 1 SD difference in the leg length/height ratio. During a mean follow-up period of 7.6 years, the age-adjusted incidence per 1,000 person years of follow-up was 25.8, 24.2, 10.4, and 16.2 in African American (AA) women, AA men, white women, and white men, respectively. The hazard ratio for diabetes (95% CI) per 5-cm difference in leg length was 0.85 (0.75-0.95) in white men, 0.79 (0.69-0.90) in white women, 0.90 (0.75-1.07) in AA women, and 0.99 (0.77-1.27) in AA men, after adjusting for age, parental history of diabetes, parental socioeconomic status, and weight at age 25. The hazard ratio for diabetes per 1 SD difference in leg length/height ratio followed the same trend. Leg length is inversely and independently related to an increased risk of diabetes in middle-age white men and women but not in African-Americans. This sex-race heterogeneity suggests that nutritional and environmental factors in childhood may modify this risk through different pathways.

Fasting plasma glucose and HbA1c as risk factors for Type 2 diabetes

We examined the value of combining fasting plasma glucose (FPG) and glycated haemoglobin (HbA(1c)) as a predictor of diabetes, using the new American Diabetes Association (ADA) criteria of FPG and lower cut-off point of HbA(1c). A retrospective cohort study was conducted from 1998 to 2006, inclusive, in 10 042 persons (55 884 person-years), with a mean age of 53.0 years at baseline. The cumulative incidence of diabetes (defined either as an FPG > or = 7.0 mmol/l or as clinically diagnosed diabetes) was measured. The cumulative incidence and incidence density of diabetes were 3.7% (368 cases) and 6.6/1000 person-years over a mean follow-up period of 5.5 years. The cumulative incidence of diabetes in subjects with impaired fasting glucose (IFG) and HbA(1c) 5.5-6.4% was 24.8% (172/694 persons) compared with 0.4% (25/6698 persons), 2.5% (15/605 persons), 7.6% (156/2045 persons) in those with normal fasting glucose (NFG) and HbA(1c) < 5.5%, NFG and HbA(1c) 5.5-6.4% and IFG and HbA(1c) < 5.5%, respectively. The hazard ratio for diabetes, adjusted for possible confounders, was 7.4 (95% confidence interval, 4.70 to 11.74) for those with NFG and HbA(1c) 5.5-6.4%, 14.4 (11.93 to 27.79) for those with IFG and HbA(1c) < 5.5% and 38.4 (24.63 to 59.88) for those with IFG and HbA(1c) 5.5-6.4%. The combination of FPG and HbA(1c) identifies individuals who are at risk of progression to Type 2 diabetes at the new ADA criteria of FPG and a lower cut-off point of HbA(1c) than previous studies.

A Prospective Study of Plasma Ferritin Level and Incident Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

The authors performed a case-cohort study nested within the Atherosclerosis Risk in Communities (ARIC) Study to determine the association between plasma ferritin level and risk of type 2 diabetes mellitus. Persons with incident cases of type 2 diabetes diagnosed over an average follow-up period of 7.9 years (n = 599) were compared with a random sample of the cohort (n = 690). After adjustment for age, gender, menopausal status, ethnicity, center, smoking, and alcohol intake, the hazard ratio for diabetes, comparing the fifth quintile of ferritin with the first quintile, was 1.74 (95% confidence interval: 1.14, 2.65; p-trend < 0.001). After further adjustment for body mass index and components of the metabolic syndrome, the hazard ratio was 0.81 (95% confidence interval: 0.49, 1.34; p-trend = 0.87). From a causal perspective, there are two alternative interpretations of these findings. Elevated iron stores, reflected in elevated plasma ferritin levels, may induce baseline metabolic abnormalities that ultimately result in diabetes. Alternatively, elevated ferritin may be just one of several metabolic abnormalities related to the underlying process that ultimately results in diabetes, rather than a causal factor for diabetes. Longitudinal studies with repeated measurements of glucose and iron metabolism parameters are needed to establish the role of iron stores and plasma ferritin in diabetes development.

Incidence of diabetes in a general practice population: a database cohort study on the relationship with haloperidol, olanzapine, risperidone or quetiapine exposure

The present study aimed to estimate the incidence of diabetes in general practice patients who were treated with haloperidol, olanzapine, risperidone or quetiapine monotherapy and in subjects who were not exposed to antipsychotics. The design was a retrospective, up to 2 years, cohort study, with age-, sex- and length of observation-matching between subjects who were exposed and not exposed to antipsychotic drugs. Data were taken from the Health Search database, which contains information from 550 Italian general practitioners. Participants comprised 2,071 subjects taking haloperidol, 266 taking olanzapine, 567 taking risperidone and 109 taking quetiapine, in addition to 6,026 age- and sex-matched subjects who were not using antipsychotic drugs during the period of observation. Inclusion was limited to initially non-diabetic and antipsychotic drug-free individuals. The main outcome measure was the incidence of drug-treated diabetes. After age and sex correction by Cox regression analysis, the four groups treated with antipsychotics significantly differed from untreated subjects in hazard ratios for diabetes. The ratios for the haloperidol, olanzapine, risperidone and quetiapine groups were 12.4 (95% confidence interval 6.3-24.5), 20.4 (6.9-60.3), 18.7 (8.2-42.8) and 33.7 (9.2-123.6), respectively, with no significant differences when compared to each other.