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OBJECTIVE This study investigated the effects of severe hypoglycemia on risks of all-cause mortality and cardiovascular disease (CVD) incidence in patients with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS Two nested case-control studies with age- and sex-matched control subjects and using the time-density sampling method were performed separately within a cohort of 10,411 patients with T1DM in Taiwan. The study enrolled 564 nonsurvivors and 1,615 control subjects as well as 743 CVD case subjects and 1,439 control subjects between 1997 and 2011. History of severe hypoglycemia was identified during 1 year, 1–3 years, and 3–5 years before the occurrence of the study outcomes. Conditional logistic regression analyses were performed to estimate the odds ratio (OR) and 95% CI of the study outcomes. RESULTS Prior severe hypoglycemic events within 1 year were associated with higher risks of all-cause mortality and CVD (adjusted OR 2.74 [95% CI 1.96–3.85] and 2.02 [1.35–3.01], respectively). Events occurring within 1–3 years and 3–5 years before death were also associated with adjusted ORs of 1.94 (95% CI 1.39–2.71) and 1.68 (1.15–2.44), respectively. Significant dose–gradient effects of severe hypoglycemia frequency on mortality and CVD were observed within 5 years. CONCLUSIONS Although the CVD incidence may be associated with severe hypoglycemic events occurring in the previous year, the risk of all-cause mortality was associated with severe hypoglycemic events occurring in the preceding 5 years. Exposure to repeated severe hypoglycemic events can lead to higher risks of mortality and CVD.

OBJECTIVE This study addresses the strength of association for the bidirectional relationship between type 2 diabetes and depression. RESEARCH DESIGN AND METHODS We used two cohort studies with the same source of database to determine the link between depression and type 2 diabetes. The data analyzed included a random sample of 1 million beneficiaries selected from the National Health Insurance claims in 2000. The analysis of diabetes predicting the depression onset consisted of 16,957 diabetic patients and the same number of sex- and age-matched nondiabetic control subjects. The analysis of depression predicting diabetes onset included 5,847 depressive patients and 5,847 sex- and age-matched nondepressive control subjects. The follow-up period was between 2000 and 2006, and onset of end points was identified from ambulatory care claims. The Cox proportional hazards regression model adjusted for potential confounders was used to estimate relative hazards. RESULTS The first cohort analysis noted an incidence density (ID) of 7.03 per 1,000 person-years (PY) and 5.04 per 1,000 PY for depression in diabetic and nondiabetic subjects, respectively, representing a covariate-adjusted hazard ratio (HR) of 1.43 (95% CI 1.16–1.77). The second cohort analysis noted an ID of 27.59 per 1,000 PY and 9.22 per 1,000 PY for diabetes in depressive and nondepressive subjects, respectively. The covariate-adjusted HR was stronger at 2.02 (1.80–2.27) for incident diabetes associated with baseline depression. CONCLUSIONS The two cohort studies provided evidence for the bidirectional relationship between diabetes and depression, with a stronger association noted for the depression predicting onset of diabetes.

OBJECTIVE Diabetes may increase the risk of acute pancreatitis (AP). We aimed to further investigate whether diabetes may also adversely affect outcomes of patients with AP. RESEARCH DESIGN AND METHODS In this retrospective cohort study, we compared 18,990 first-attack AP with diabetes to 37,980 matched control subjects from Taiwan’s National Health Insurance Research Database between 2000 and 2009. Primary outcomes were development of severe AP, defined by a modified Atlanta classification scheme, and hospital mortality. Analyses were performed using univariable and multivariable logistic regression model with generalized estimating equations accounting for hospital clustering effect. RESULTS After baseline characteristics were adjusted, AP patients with diabetes had a higher risk of a severe attack than their nondiabetic counterparts (adjusted odds ratio [OR] 1.21, 95% CI 1.16–1.26). When severity criteria were analyzed individually, diabetic AP patients had a 58% higher risk of intensive care unit admission and a 30% higher risk of local complications, but a 16% lower risk of gastrointestinal bleeding, than AP patients without diabetes. The risk of organ failure at least one system) was similar between the two groups. Conversely, AP patients with diabetes were associated with a lower risk of hospital mortality (adjusted OR 0.77, 95% CI 0.65–0.91). CONCLUSIONS Although diabetes may adversely affect the disease process of AP, it seems to protect patients from AP-related mortality.

OBJECTIVE—Using Taiwan's National Health Insurance claim data, we evaluated the age-, sex-, and urbanization-specific incidence density and relative risks of hip fracture in the diabetic population. RESEARCH DESIGN AND METHODS—Diabetic patients (n = 500,868) and an age- and sex-matched control group (n = 500,248) were linked to inpatient claims (1997–2002) to identify hospitalizations for nontransport accident hip fracture. The person-year approach with Poisson assumption and Kaplan-Meier analysis were used to estimate the incidence and the cumulative event rates. We also assessed the age-, sex-, and urbanization-specific relative risks of hip fracture in relation to diabetes with the Cox proportional hazard regression model. RESULTS—The overall incidences of hip fracture for diabetic men and women, respectively, were 3.01 and 6.75/1,000 person-years, which were higher than those for control men and women. There were significant interactions of diabetes and age and diabetes and urbanization statuses. Hazard ratios (HRs) of diabetic patients aged 35–44 years (men 2.45 [95% CI 1.65–3.64]; women 3.19 [1.39–7.33]) were higher than those of diabetic patients aged 55–64 years (men 1.90; women 2.81), but in diabetic men aged >74 years and diabetic women aged >84 years, the HRs were compared with null statistically (HRs 0.98 and 0.91, respectively). Diabetic patients living in rural areas tended to have higher HRs of hip fracture. CONCLUSIONS—In Taiwan, diabetes increased the risk of hip fracture in both sexes in all age-groups except in diabetic men aged >74 years and diabetic women aged >84 years. Higher HRs of hip fracture were disproportionately observed in younger diabetic patients and in those living in rural areas.

OBJECTIVE—Using the National Health Insurance claim data, we prospectively investigated the age- and sex-specific incidence density and relative hazards of nontraumatic lower-extremity amputation (LEA) and peripheral revascularization procedure (PRP) of the diabetic population in Taiwan. RESEARCH DESIGN AND METHODS—A total of 500,868 diabetic patients and 500,248 age- and sex-matched control subjects, selected from the ambulatory care claim (1997) and the registry for beneficiaries, respectively, were linked to inpatient claims (1997–2002) to identify hospitalizations due to nontraumatic LEA and PRP. Incidence density was calculated under the Poisson assumption, and the Kaplan-Meier analysis was used to assess the cumulative event rates over a 6-year follow-up period. We also evaluated the age- and sex-specific relative hazards of nontraumatic LEA and PRP in relation to diabetes with Cox proportional hazard regression model adjusted for demographics and regional areas. RESULTS—The estimated incidence density of nontraumatic LEA and PRP for diabetic men was 410.3 and 317.0 per 100,000 patient-years, respectively. The corresponding data for diabetic women were relatively low at 115.2 and 86.0 per 100,000 patient-years. Compared with control subjects with the same age and sex, diabetic patients consistently suffered from significantly elevated relative hazards of nontraumatic LEA. Young and female patients were especially vulnerable to experience increased risks of nontraumatic LEA, but such effect modification by age and sex was less apparent for PRP. CONCLUSIONS—Multidisciplinary diabetes foot care systems, including the provision of revascularization procedures, should be further enforced to reduce subsequent risks of nontraumatic LEA, especially in young and female diabetic patients.

OBJECTIVE—To study the effect of birth weight on risk of type 2 diabetes in the schoolchildren in Taiwan. RESEARCH DESIGN AND METHODS—From 1992 to 1997, all schoolchildren aged 6–18 years were screened for diabetes in Taiwan Province. This cohort consisted of 1,966 patients with diabetes and 1,780 randomly selected subjects with normal fasting glycemia (NFG). Questionnaire interviewing was designed to classify diabetes. The birth weight was obtained from the Taiwan’s Birth Registry. After merging the data, there were 978 subjects, including 429 with type 2 diabetes and 549 with of NFG enrolled in the present analyses. RESULTS—The odds ratios (95% CI) for type 2 diabetes, after adjusting age, sex, BMI, family history of diabetes, and socioeconomic status, were 2.91 (1.25–6.76) for children with low birth weight ( CONCLUSIONS—A U-shaped relationship between birth weight and risk of type 2 diabetes was found in the schoolchildren aged 6–18 years in Taiwan. Schoolchildren with type 2 diabetes who were born with low birth weight had different metabolic phenotypes compared with those born with high birth weight.

OBJECTIVE We retrospectively assessed the age- and sex-specific incidence and relative risk of Parkinson disease (PD) in Taiwan’s diabetic population. RESEARCH DESIGN AND METHODS Study cohort included 603,416 diabetic patients and 472,188 nondiabetic control subjects. Incidence rate and relative risk of PD (ICD-9-CM 332.0) were evaluated. RESULTS The incidence of PD was 3.59 and 2.15 per 10,000 person-years for the diabetic and control group, respectively, representing a covariate adjusted hazard ratio (HR) of 1.61 (95% CI 1.56–1.66), which was substantially reduced to 1.37 (1.32–1.41) after adjusting for medical visits. Diabetes was associated with a significantly elevated risk of PD in all sex and age stratifications except in young women, with the highest HR noted for young men aged 21–40 years (2.10 [1.01–4.42]), followed by women aged 41–60 (2.05 [1.82–2.30]) and >60 years (1.65 [1.58–1.73]). CONCLUSIONS Diabetes is associated with an increased risk of PD onset in a Chinese population, and the relation is stronger in women and younger patients.

OBJECTIVE We prospectively assessed the age- and sex-specific incidence and relative risk of malignant neoplasm of the pancreas in Taiwan’s diabetic population. RESEARCH DESIGN AND METHODS A total of 615,532 diabetic patients and 614,871 age- and sex-matched control subjects were linked to inpatient claims (2000–2006) to identify the admissions for malignant neoplasm of the pancreas (ICD-9: 157). The Cox proportional hazards regression model was used to estimate the age- and sex-specific relative risk of pancreatic neoplasm. RESULTS Compared with the control group, the diabetic patients had a significantly increased risk of pancreatic cancer (hazard ratio [HR] 1.54 [95% CI 1.39–1.71]). The higher and significant age-specific HRs were observed in diabetic men (1.91) and women (1.80) aged 45–65 years. CONCLUSIONS Middle-aged diabetic men and women were associated with the most increased risk of malignant neoplasm of the pancreas.