Thomas Ransom

The relationship between bipolar disorder and type 2 diabetes: More than just co-morbid disorders

Abstract Type 2 diabetes mellitus (T2DM) rates are three times higher in patients with bipolar disorder (BD), compared to the general population. This is a major contributing factor to the elevated risk of cardiovascular mortality, the leading cause of death in bipolar patients. There may be shared pathophysiology linking the two disorders, including hypothalamic-pituitary-adrenal and mitochondrial dysfunction, common genetic links, and epigenetic interactions. Life-style, phenomenology of bipolar symptoms, and adverse effects of pharmacotherapy may be contributing factors. Patients with BD and T2DM have a more severe course of illness and are more refractory to treatment. Control of their diabetes is poorer when compared to diabetics without BD, and an existing disparity in medical care may be partly responsible. Glucose abnormalities in bipolar patients need to be screened for and treated. Metformin appears to have the best benefit/risk ratio, and the dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists and analogues also appear promising, although these agents have not been specifically studied in populations with mood disorders. Physicians need to be aware of the increased risk for T2DM and cardiovascular disease in bipolar patients, and appropriate prevention, screening, case finding, and treatment is recommended.

Anemia is an independent risk for mortality after acute myocardial infarction in patients with and without diabetes

IntroductionAnemia and diabetes are risk factors for short-term mortality following an acute myocardial infarction(AMI). Anemia is more prevalent in patients with diabetes. We performed a retrospective study to assess the impact of the combination of diabetes and anemia on post-myocardial infarction outcomes.MethodsData relating to all consecutive patients hospitalized with AMI was obtained from a population-based disease-specific registry. Patients were divided into 4 groups: diabetes and anemia (group A, n = 716), diabetes and no anemia (group B, n = 1894), no diabetes and anemia (group C, n = 869), and no diabetes and no anemia (group D, n = 3987). Mortality at 30 days and 31 days to 36 months were the main outcome measures.Results30-day mortality was 32.3% in group A, 16.1% in group B, 21.5% in group C, 6.6% in group D (all p < 0.001). 31-day to 36-month mortality was 47.6% in group A, 20.8% in group B, 34.3% in group C, and 10.4% in group D (all p < 0.001). Diabetes and anemia remained independent risk factors for mortality with odds ratios of 1.61 (1.41–1.85, p < 0.001) and 1.59 (1.38–1.85, p < 0.001) respectively at 36 months. Cardiovascular death from 31-days to 36-months was 43.7% of deaths in group A, 54.1% in group B, 47.0% in group C, 50.8% group D (A vs B, p < 0.05).InterpretationPatients with both diabetes and anemia have a significantly higher mortality than those with either diabetes or anemia alone. Cardiovascular death remained the most likely cause of mortality in all groups.

Impact of admission serum glucose level on in-hospital outcomes following coronary artery bypass grafting surgery

OBJECTIVE The impact of admission serum glucose (SG) level on outcomes in coronary artery bypass grafting (CABG) surgery is unknown. The present study sought to determine whether elevated admission SG level is associated with adverse outcomes following CABG surgery. METHODS Patients undergoing CABG surgery between January 2000 and December 2005 at a single centre were identified (n=2856). Admission SG levels of less than 9.2 mmol/L and 9.2 mmol/L or greater were chosen to divide patients into two groups based on the 75th percentile of SG distribution. A logistic regression model was generated to determine the impact of admission SG level on a composite outcome of any one or more of in-hospital mortality, stroke, perioperative myocardial infarction, sepsis, deep sternal wound infection, renal failure, requirement for postoperative inotropes and prolonged ventilation. RESULTS In total, 76.3% of patients had an admission SG level of less than 9.2 mmol/L (group A) and 23.7% had an admission SG level of 9.2 mmol/L or greater (group B). Group B patients were more likely to be female, have diabetes, have preoperative renal failure, have an ejection fraction of less than 40%, experience myocardial infarction within 21 days before surgery, and have triple vessel or left main disease (P<0.05). Univariate analysis revealed no difference in in-hospital mortality between group A (2.2%) and group B (3.2%) (P=0.12); however, the composite outcome was more likely to occur in group B (40.8%) versus group A (27.9%) (P=0.0001). After multivariable adjustment, admission SG level of 9.2 mmol/L or greater remained an independent predictor of composite outcome (OR=1.3, 95% CI 1.0 to 1.7, P=0.02, receiver operating characteristic = 78%). CONCLUSION Admission SG level of 9.2 mmol/L or greater is associated with significant morbidity in patients undergoing CABG surgery.

Role of the fractalkine receptor CX3CR1 polymorphisms V249I and T280M as risk factors for early‐onset coronary artery disease in patients with no classic risk factors

Objectives. CX3CR1 is a monocyte chemokine receptor and adhesion molecule. Two CX3CR1 mutations, V249I and T280M, reportedly decrease coronary artery disease (CAD) risk independent of established risk factors. An I249 protective effect is attributed to reducing CX3CR1 binding to fractalkine, its ligand. Material and methods. We examined the frequencies of V249I and T280M among early‐onset CAD patients (G1; n = 149; <50 years), late‐onset CAD patients (G2; n = 150; >65 years) and healthy controls (HC; n = 149, 47–93 years) without known CAD risk factors. We compared plasma total cholesterol (TC)/high density lipoprotein‐C (HDL‐C) and apolipoprotein B (APOB)/apolipoprotein AI (APOAI) ratios among the groups and mutation carriers and non‐carriers, and the prevalence of the mutations in G1 and G2 patients with multiple coronary vessel disease (MVD) and myocardial infarction (MI). Results. G1 patients had non‐significantly lower frequencies of I249 versus (vs.) G2 or controls (G1; 51 %, G2: 61 %, controls: 58 %, p = 0.19), with no difference in T280M (p = 0.8). TC/HDL‐C and APOB/APOAI ratios were significantly higher in G1 patients vs. G2 and controls (p<0.0001) independently of either mutation. More G2 patients had MVD than younger ones (p<0.0001); however, more G1 patients were homozygous for V249 compared to G2 patients, who more often had the I249 allele (p<0.02). There was no such association with T280M (p = 0.38). Although more G1 patients had MI, this was not mutation related. Conclusions. There were significantly higher lipid ratios in G1 compared to G2 and HC (G1>G2>HC), but not in mutation prevalence. I249 mutation was associated with MVD in older patients, while V249 homozygosity was associated with the early‐onset CAD. Neither allele affected MI or lipid levels.

Outcome of stereotactic radiotherapy for patients with uncontrolled acromegaly.

OBJECTIVE Linear accelerator based stereotactic radiation therapy (SRT) has been used for the treatment of pituitary tumours; however, little is known concerning the use of this modality for the treatment of patients with acromegaly. We have prospectively studied the short-term outcome of SRT in 12 acromegaly patients who failed to achieve biochemical remission despite surgery and/or pharmacologic therapy. METHODS We identified all patients who had biochemically uncontrolled acromegaly and were treated with SRT between April 2003 and December 2006. All patients were followed prospectively based on a pre-defined protocol that included Goldman visual field examination, MRI of the sella, and pituitary hormone testing at 3, 6, 12 months, and then yearly. RESULTS A total of 12 patients with acromegaly were treated with SRT. There were 9 females and the median age of the group was 50 years. The median follow-up was 28.5 months during which time the mean tumor volume decreased by 40%, the median GH fell from 4.1 microg/L to 1.3 microg/L (p = 0.003) and the median IGF-1 dropped more than half from 545.5 microg/L to 260.5 microg/L (p = 0.002). Four patients achieved normal, while an additional 2 achieved near-normal, IGF-1 levels. One patient was able to discontinue and two were able to reduce their acromegaly medications while maintaining a normal IGF-1. A new pituitary hormonal deficit was found at 24 months in one patient who developed hypoadrenalism requiring corticosteroid replacement. CONCLUSION Based on our early experience, we believe that SRT should be considered in treating patients with uncontrolled acromegaly.

Patient Perceptions of Islet Transplantation for Type 1 Diabetes

ABSTRACT OBJECTIVE To determine the demand for islet transplantation among patients with type 1 diabetes. METHODS Surveys were mailed to patients with type 1 diabetes at 2 centres: 1 with an islet transplantation program (Vancouver, British Columbia) and another without a program (Halifax, Nova Scotia). The primary outcome was patient acceptance of islet transplantation after learning about the risks and benefits. RESULTS Of the 588 responses from a sample of 1499, 451 (76.7%) would accept or probably accept islet transplantation. Most common reasons for acceptance were 1) fewer diabetes-related complications (92.7%); 2) decreased hypoglycemia (78.5%); and 3) no insulin injections (75.0%). The rest, 137 (23.3%) respondents, would not or probably not accept islet transplantation because of 1) immunosuppressant medications (90.6%); 2) risks not yet identified (58.8%). Most would not consider islet transplantation a failure if insulin was required post-transplant (71%). Acceptance was higher among those who were younger and had less formal education and a lower household income. Patients who would accept islet transplantation had higher glycated hemoglobin, used higher doses of insulin and had worse perceived diabetes control and general health. CONCLUSIONS The majority of patients with type 1 diabetes surveyed for this study would accept islet transplantation, with expectations of fewer complications, decreased hypoglycemia and freedom from insulin.

Development and implementation of diabetes guidelines for elderly residents in long-term care facilities in Nova scotia.

| 285 urban Haitian population illustrates the need for screening for MS in hypertensive subjects at initial diagnosis or first medical visit. The very strong association between abdominal obesity and reduced HDL cholesterol in hypertensive patients drastically increases the probability of MS in presence of the combination hypertension and abdominal obesity.