Insulin versus oral agents in the management of Cystic Fibrosis Related Diabetes: a case based study

BACKGROUND: Insulin is the recommend therapeutic agent of choice for the management of Cystic Fibrosis Related Diabetes (CFRD), despite only sub-optimal reductions in glycemic control and increased morbidity and mortality reported by centers using this agent. The newer insulin sensitizing agents demonstrated to have anti-inflammatory mechanisms may provide an alternative management option for CFRD. METHODS: A prospective case based therapeutic comparison between insulin, sulfonylurea, metformin and thiazolidinedione was observed over one decade with 20 CFRD patients diagnosed using American Diabetes Association guideline standards. Patients entering the study elected treatment based on risk and benefit information provided for treatment options. Patients receiving organ transplant or requiring combination diabetic medications were excluded from the study. RESULTS: No statistical advantage was achieved regarding overall glycemic control for oral agents over insulin. Additional outcome measures including changes in weight, liver function testing and FEV(1 )were not statistically significant. CONCLUSION: Insulin alone may not be the only therapeutic option in managing CFRD. Oral hypoglycemic agents were equally effective in treating CFRD and may provide an alternative class of agents for patients reluctant in using insulin

Metformin treatment in diabetes and heart failure: when academic equipoise meets clinical reality

<p>Abstract</p> <p>Objective</p> <p>Metformin has had a 'black box' contraindication in diabetic patients with heart failure (HF), but many believe it to be the treatment of choice in this setting. Therefore, we attempted to conduct a pilot study to evaluate the feasibility of undertaking a large randomized controlled trial with clinical endpoints.</p> <p>Study Design</p> <p>The pilot study was a randomized double blinded placebo controlled trial. Patients with HF and type 2 diabetes were screened in hospitals and HF clinics in Edmonton, Alberta, Canada (population ~1 million). Major exclusion criteria included the current use of insulin or high dose metformin, decreased renal function, or a glycosylated hemoglobin <7%. Patients were to be randomized to 1500 mg of metformin daily or matching placebo and followed for 6 months for a variety of functional outcomes, as well as clinical events.</p> <p>Results</p> <p>Fifty-eight patients were screened over a six month period and all were excluded. Because of futility with respect to enrollment, the pilot study was abandoned. The mean age of screened patients was 77 (SD 9) years and 57% were male. The main reasons for exclusion were: use of insulin therapy (n = 23; 40%), glycosylated hemoglobin <7% (n = 17; 29%) and current use of high dose metformin (n = 12; 21%). Overall, contraindicated metformin therapy was the most commonly prescribed oral antihyperglycemic agent (n = 27; 51%). On average, patients were receiving 1,706 mg (SD 488 mg) of metformin daily and 12 (44%) used only metformin.</p> <p>Conclusion</p> <p>Despite uncertainty in the scientific literature, there does not appear to be clinical uncertainty with regards to the safety or effectiveness of metformin in HF making a definitive randomized trial virtually impossible.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00325910</p

Determinants of urinary albumin excretion within the normal range in patients with type 2 diabetes: the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study

In contrast to microalbuminuric type 2 diabetic patients, the factors correlated with urinary albumin excretion are less well known in normoalbuminuric patients. This may be important because even within the normoalbuminuric range, higher rates of albuminuria are known to be associated with higher renal and cardiovascular risk. At the time of screening for the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) Study, the urinary albumin/creatinine ratio (UACR) was 0.44 mg/mmol in 4,449 type 2 diabetic patients. The independent correlates of UACR were analysed. Independent correlates of UACR during baseline were (in descending order): night-time systolic BP (r (s) = 0.19); HbA(1c) (r (s) = 0.18); mean 24 h systolic BP (r (s) = 0.16); fasting blood glucose (r (s) = 0.16); night-time diastolic BP (r (s) = 0.12); office systolic BP, sitting (r (s) = 0.11), standing (r (s) = 0.10); estimated GFR (r (s) = 0.10); heart rate, sitting (r (s) = 0.10); haemoglobin (r (s) = -0.10); triacylglycerol (r (s) = 0.09); and uric acid (r (s) = -0.08; all p a parts per thousand currency signaEuro parts per thousand 0.001). Significantly higher albumin excretion rates were found for the following categorical variables: higher waist circumference (more marked in men); presence of the metabolic syndrome; smoking (difference more marked in males); female sex; antihypertensive treatment; use of amlodipine; insulin treatment; family history of diabetes; and family history of cardiovascular disease (more marked in women). Although observational correlations do not prove causality, in normoalbuminuric type 2 diabetic patients the albumin excretion rate is correlated with many factors that are potentially susceptible to intervention. ClinicalTrials.gov ID no.: NCT00185159 This study was sponsored by Daichii-Sankyo.Nephrolog

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain

Therapeutic approach to FSGS in children

Therapy of primary focal segmental glomerulosclerosis (FSGS) in children incorporates conservative management and immunosuppression regimens to control proteinuria and preserve kidney function. In long-term cohort studies in adults and children with primary FSGS, renal survival has been directly associated with degree of proteinuria control. This educational article reviews the current therapeutic approach toward children with primary FSGS

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Background: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. Approach: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. Content: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A$_{1c}$ (HbA$_{1c}$) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA$_{1c}$. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. Summary: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended