Metformin use and cirrhotic decompensation in patients with type 2 diabetes and liver cirrhosis.

AIMS: To compare the risks of all-cause mortality, hepatic outcomes, major adverse cardiovascular events between metformin users and nonusers for patients with diabetes and cirrhosis. METHODS: From the Taiwan's National Health Insurance Research Database, we selected propensity-score matched metformin users and nonusers from the cohorts of type 2 diabetes mellitus with compensated (n = 26 164) or decompensated liver cirrhosis (n = 15 056) between 1 January 2000 and 31 December 2009, and followed them until 31 December 2010. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risk of investigated outcomes for metformin users. RESULTS: The incidence rates of mortality during follow-up were 3.8 and 3.3 per 100 patient-years (adjusted hazard ratio [aHR] 1.13, 95% confidence interval 1.01-1.25) for metformin users and nonusers, respectively. The incidence rates of cirrhotic decompensation during follow-up were 5.9 and 4.9 per 100 patient-years (aHR 1.15, 95% confidence interval 1.04-1.27) for metformin users and nonusers. The risk of death (P for trend <.01) and cirrhotic decompensation (P for trend <.0001) associated with metformin use was significant for those taking metformin for >40 defined daily doses in 90 days or >1000 mg/d. The outcomes of metformin use vs nonuse for type 2 diabetes mellitus with decompensated liver cirrhosis were not statistically different, except that metformin users had higher risk of mortality (aHR 1.15). CONCLUSION: Metformin use was associated with higher risks of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis. Prospective studies are required to confirm our results.

Vitamin D supplementation worsens Alzheimer's progression: Animal model and human cohort studies.

Vitamin D deficiency has been epidemiologically linked to Alzheimer's disease (AD) and other dementias, but no interventional studies have proved causality. Our previous work revealed that the genomic vitamin D receptor (VDR) is already converted into a non-genomic signaling pathway by forming a complex with p53 in the AD brain. Here, we extend our previous work to assess whether it is beneficial to supplement AD mice and humans with vitamin D. Intriguingly, we first observed that APP/PS1 mice fed a vitamin D-sufficient diet showed significantly lower levels of serum vitamin D, suggesting its deficiency may be a consequence not a cause of AD. Moreover, supplementation of vitamin D led to increased Aß deposition and exacerbated AD. Mechanistically, vitamin D supplementation did not rescue the genomic VDR/RXR complex but instead enhanced the non-genomic VDR/p53 complex in AD brains. Consistently, our population-based longitudinal study also showed that dementia-free older adults (n = 14,648) taking vitamin D3 supplements for over 146 days/year were 1.8 times more likely to develop dementia than those not taking the supplements. Among those with pre-existing dementia (n = 980), those taking vitamin D3 supplements for over 146 days/year had 2.17 times the risk of mortality than those not taking the supplements. Collectively, these animal model and human cohort studies caution against prolonged use of vitamin D by AD patients.

Early-onset type 2 diabetes <60 years and risk of vascular complications.

AIM: To compare long-term outcomes among three groups with different ages of diabetes onset. METHOD: 66,520 paired age-, and sex-matched persons with and without type 2 diabetes were selected from the Taiwan National Health Insurance Research Database from 2000 to 2012. Cox proportional hazards models were used to compare the outcomes. Using late-onset diabetes as a reference, adjusted difference in differences analyses were performed to assess excessive odds comparing diabetes versus non-diabetes for young-onset diabetes (YOD) and early-onset diabetes in the risks of mortality and vascular complications. RESULTS: Persons with type 2 diabetes, irrespective of the onset age, had higher associated risks of all-cause mortality and vascular complications than their matched counterparts without diabetes. Compared to the odds of complications between those with diabetes and non-diabetes in the late-onset diabetes group, the excess odds in YOD are generally greater than in the early-onset diabetes (for stroke: 1.90 vs. 1.32; heart failure: 2.03 vs. 1.58; myocardial infarction: 3.02 vs. 1.56; and microvascular complications: 3.52 vs. 3.01). CONCLUSIONS: Diabetes with different ages of onset may imply distinct long-term health outcomes. The persons with young-onset and early-onset diabetes seem to bear excess risk for mortality and vascular complications.

Psychotropic use and risk of stroke among patients with bipolar disorders: 10-year nationwide population based study.

OBJECTIVES: To investigate the association between psychotropic agents (including antipsychotics, antidepressants and mood stabilizers) and risk of stroke among patients with bipolar disorders. METHODS: We conducted a disease risk score-matched nested case-control study and identified patients with bipolar disorders (ICD-9 codes: 296.0x, 296.1x, 296.4x, 296.5x, 296.6x, 296.7x, 296.80, 296.81 or 296.89) from the National Health Insurance Research Database in Taiwan. Among them, we identified 1232 cases (981 were ischemic stroke and 251 were hemorrhagic stroke) and 5314 disease risk score-matched controls. Conditional logistic regression model equations were applied to determine the effect of psychotropic agents on stroke risk among patients with bipolar disorders. RESULTS: The results indicated that overall use of psychotropic agents was associated with an increased risk of stroke (adjusted odds ratio [AOR] = 1.82; 95% confidence interval [CI]: 1.56-2.13). When classifying psychotropic agents into antipsychotics, antidepressants and mood stabilizers, respectively, a significant positive association was found for users of antipsychotics (AOR = 1.98; 95% CI = 1.53-2.56), antidepressants (AOR = 1.44; 95% CI = 1.16-1.79), and mood stabilizers (AOR = 1.89; 95% CI = 1.22-2.93). Combined use of psychotropic agents was associated with higher risk of stroke than monotherapy (AOR = 2.62; 95% CI = 1.98-3.45). DISCUSSIONS: The results support our hypothesis that psychotropic use is associated with increased risk of stroke among patients with bipolar disorders. The stroke risks are higher among patients with polypharmacy than those with monotherapy. These findings warrant further investigation to confirm and replicate the findings using different methodologies and populations, and to mitigate residual confounding.

Association of Nonsteroidal Anti-inflammatory Drug Use With Stroke Among Dialysis Patients.

INTRODUCTION: Limited studies have evaluated risk of stroke associated with the use of NSAIDs in patients with end-stage kidney disease. We examined the adverse effects of selective and nonselective NSAID use on the risk of stroke in dialysis patients. METHODS: A case-crossover study was conducted using medical claims data from the National Health Insurance Research Database in Taiwan. We identified patients with ischemic and hemorrhagic stroke (defined as International Classification of Diseases, 9th revision, Clinical Modification codes 433, 434, and 436 for ischemic stroke and 430 and 431 for hemorrhagic stroke) from inpatient claims during the period from 2003 to 2012. Conditional logistic regression models with adjustment for potential confounders were used to determine the effects of NSAID use on stroke. RESULTS: A total of 1190 dialysis patients with stroke were identified from 2003 to 2012. The results indicate a 1.31-fold increased risk of stroke related to NSAID use during the 30 days prior to a stroke (AOR = 1.31; 95% CI: 1.03-1.66); likewise, an excessive risk of ischemic stroke was observed (AOR = 1.34; 95% CI: 1.02-1.77). When classifying NSAIDs into selective and nonselective groups, nonselective NSAID use was significantly associated with an increased risk of stroke (AOR = 1.27; 95% CI: 1.00-1.61). DISCUSSION: In summary, the results show supportive evidence that NSAID use increased the risk of stroke in dialysis patients, which suggests the importance of closely monitoring the transient effects of initial NSAID treatment to patients on dialysis.