A Systematic Review of Evidence on the Use of Very Low Calorie Diets in People with Diabetes.

BACKGROUND: Recent interest has emerged regarding the effects of Very Low Calorie Diet (VLCD) in people with type 2 diabetes (T2D). We therefore performed a systematic review to investigate the effects of VLCD on HbA1c, weight and cardiovascular risk profile outcomes as well as its safety and tolerability among people with T2D. METHODS: We conducted searches of Cochrane Database of Systematic Reviews, Centre for reviews and Dissemination databases, Medline, Embase, Pubmed, Web of Science, Web of Knowledge and Turning Research into Practice (TRIP) as well as ongoing trial resources. We included all studies involving VLCD and diabetes published until December 2013. Outcome measures include weight, HbA1c, fasting glucose, fasting insulin, lipid profile, blood pressure, safety and drop out rates. RESULTS: 17 studies were included in the systematic review. Duration of VLCD duration ranged from 5 days to 6 months and duration of follow up ranged from 8 days to 5 years. The age range was 14 years to 59 years of age. Mean weight loss was 13.2kg, ranging from 4.1 to 24kg. Mean Hba1c reduction was 1.4% (ranging between 0.1 to 3.1% reduction across different studies). Three studies reported a significant reduction in the daily doses of insulin. All studies which reported cardiovascular risk profile showed a significant decrease in total cholesterol, systolic and diastolic blood pressure post VLCD. Apart from two studies, all of the other studies showed that the decrease in blood pressure and total cholesterol was not only present immediately post VLCD, but it was also maintained at follow up. However it is important to note that the follow up periods did differ between studies. Overall, drop out rates ranged from 4.7% to 33% and appeared to be lower during the active intervention phase compared with during the follow-up period. No major adverse event was reported apart from one study which recorded a non-fatal myocardial infarction. CONCLUSION: This review demonstrated that VLCD in people with T2D was associated with significant weight loss, reduction in blood glucose profile and improvement in cardiovascular risk profile, high tolerability and good safety outcomes. Studies were heterogeneous and longer term outcomes data post VLCD is still required.

Grader agreement, and sensitivity and specificity of digital photography in a community optometry-based diabetic eye screening program.

BACKGROUND: Digital retinal photography with mydriasis is the preferred modality for diabetes eye screening. The purpose of this study was to evaluate agreement in grading levels between primary and secondary graders and to calculate their sensitivity and specificity for identifying sight-threatening disease in an optometry-based retinopathy screening program. METHODS: This was a retrospective study using data from 8,977 patients registered in the North Nottinghamshire retinal screening program. In all cases, the ophthalmology diagnosis was used as the arbitrator and considered to be the gold standard. Kappa statistics were used to evaluate the level of agreement between graders. RESULTS: Agreement between primary and secondary graders was 51.4% and 79.7% for detecting no retinopathy (R0) and background retinopathy (R1), respectively. For preproliferative (R2) and proliferative retinopathy (R3) at primary grading, agreement between the primary and secondary grader was 100%. Where there was disagreement between the primary and secondary grader for R1, only 2.6% (n=41) were upgraded by an ophthalmologist. The sensitivity and specificity for detecting R3 was 78.2% and 98.1%, respectively. None of the patients upgraded from any level of retinopathy to R3 required photocoagulation therapy. The observed kappa between the primary and secondary grader was 0.3223 (95% confidence interval 0.2937-0.3509), ie, fair agreement, and between the primary grader and ophthalmology for R3 was 0.5667 (95% confidence interval 0.4557-0.6123), ie, moderate agreement. CONCLUSION: These data provide information on the safety of a community optometry-based retinal screening program for screening as a primary and as a secondary grader. The level of agreement between the primary and secondary grader at a higher level of retinopathy (R2 and R3) was 100%. Sensitivity and specificity for R3 were 78.2% and 98.1%, respectively. None of the false-negative results required photocoagulation therapy.

Inhaled corticosteroids and bone health.

Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease.

Stimulation of lactate production in human granulosa cells by metformin and potential involvement of adenosine 5' monophosphate-activated protein kinase.

CONTEXT: Production of 3-carbon units (as lactate) by granulosa cells (GCs) is important in follicular and oocyte development and may be modulated by metformin. OBJECTIVE: The aim of the study was to examine the action of metformin on GC lactate production and potential mediation via AMP-activated protein kinase (AMPK). DESIGN: GCs were prepared from follicular aspirates. After exposure to metformin and other potential modulators of AMPK in culture, aspects of cellular function were examined. SETTING: The study was conducted in a private fertility clinic/university academic center. PATIENTS: Women undergoing routine in vitro fertilization participated in the study. INTERVENTIONS: All agents were added in culture. MAIN OUTCOME MEASURES: Lactate output of GCs was measured. Cell extracts were prepared after culture, and phosphorylated forms of AMPK and acetyl CoA carboxylase (ACC) were assayed using Western analysis. RESULTS: Metformin led to a rapid increase in lactate production by GCs [minimum effective dose, 250 microm; maximum dose studied, 1 mm (1.22-fold; P < 0.01)]. This dose range of metformin was similar to that required for stimulation of phospho-AMPK in GCs [minimum effective dose, 250 microm; maximum effect, 500 microm (2.01-fold; P < 0.001)]. Increasing phospho-ACC, as a representative downstream target regulated by AMPK, was apparent over a lower range (minimum effective dose, 31 microm; maximum effect, 250 microm; P < 0.001). A level of metformin (125 microm) insufficient for the stimulation of lactate output when used alone potentiated the effects of suboptimal doses of insulin on lactate production. Adiponectin (2.5 microg/ml) had a small but significant effect on lactate output. CONCLUSIONS: Metformin activates AMPK in GCs, stimulating lactate production and increasing phospho-ACC. Metformin also enhances the action of suboptimal insulin concentrations to stimulate lactate production.