Clinically meaningful and lasting HbA1c improvement rarely occurs after 5 years of type 1 diabetes: an argument for early, targeted and aggressive intervention following diagnosis.

AIMS/HYPOTHESIS: Our objectives were to explore whether the phenomenon of HbA1c 'tracking' occurs in individuals with type 1 diabetes, how long after diagnosis does tracking take to stabilise, and whether there is an effect of sex and age at diagnosis on tracking. METHODS: A total of 4525 individuals diagnosed with type 1 diabetes between 1 January 1995 and 1 May 2015 were identified from The Health Improvement Network (THIN) database. Mixed models were applied to assess the variability of HbA1c levels over time with random effects on general practices (primary care units) and individuals within practices. RESULTS: 4525 individuals diagnosed with type 1 diabetes were identified in THIN over the study period. The greatest difference in mean HbA1c measurement (-7.0 [95% CI -8.0, -6.1] mmol/mol [0.6%]) was seen when comparing measurements made immediately after diagnosis (0-1 year since diagnosis) with those at 10 or more years (the reference category). The mean difference in HbA1c for the successive periods compared with 10 or more years after diagnosis declined and was no longer statistically significant after 5 years. In the stratified analysis using sex and age group there was considerable heterogeneity with adult onset type 1 diabetes appearing to track earlier and at a lower mean HbA1c. CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes, glycaemic control measured by HbA1c settles onto a long-term 'track' and this occurs on average by 5 years following diagnosis. Age at diagnosis modifies both the rate at which individuals settle into their track and the absolute HbA1c tracking level for the next 10 years

Long-term treatment of osteoporosis: safety and efficacy appraisal of denosumab

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised

The Impact of Bariatric Surgery on Incident Microvascular Complications in Patients With Type 2 Diabetes: A Matched Controlled Population-Based Retrospective Cohort Study

To assess the impact of bariatric surgery (BS) on incident microvascular complications of diabetes-related foot disease (DFD), sight-threatening diabetic retinopathy (STDR), and chronic kidney disease (CKD) in patients with type 2 diabetes and obesity. A retrospective matched, controlled population-based cohort study was conducted of adults with type 2 diabetes between 1 January 1990 and 31 January 2018 using IQVIA Medical Research Data (IMRD), a database of primary care electronic records. Each patient with type 2 diabetes who subsequently had BS (surgical group) was matched on the index date with up to two patients with type 2 diabetes who did not have BS (nonsurgical group) within the same general practice by age, sex, preindex BMI, and diabetes duration. Included were 1,126 surgical and 2,219 nonsurgical participants. In the study population 2,261 (68%) were women. Mean (SD) age was 49.87 (9.3) years vs. 50.12 (9.3) years and BMI was 46.76 (7.96) kg/m vs. 46.14 (7.49) kg/m in the surgical versus nonsurgical group, respectively. In the surgical group, 22.1%, 22.7%, 52.2%, and 1.1% of patients had gastric band, sleeve gastrectomy, Roux-en-Y gastric bypass (RYGB), and duodenal switch, respectively. Over a median follow-up of 3.9 years (interquartile range 1.8-6.4), BS was associated with reduction in incident combined microvascular complications (adjusted hazard ratio 0.53, 95% CI 0.43-0.66, <0.001), DFD (0.61, 0.50-0.75, <0.001), STDR (0.66, 0.44-1.00, = 0.048), and CKD (0.63, 0.51-0.78, <0.001). Analysis based on the type of surgery showed that all types of surgery were associated with a favorable impact on the incidence of composite microvascular complications, with the greatest reduction for RYGB. BS was associated with a significant reduction in incident diabetes-related microvascular complications. [Abstract copyright: © 2020 by the American Diabetes Association.

Discriminatory performance of adiponectin and leptin in the identification of impaired glucose tolerance:The Guangzhou Biobank Cohort Study - Cardiovascular Disease Subcohort

BackgroundTo evaluate the additional discriminatory performance of adiponectin, leptin, and their ratio in the identification of impaired glucose tolerance (IGT) in men and women without diabetes on top of conventional risk factors.Methods & resultsA total of 698 subjects underwent an oral glucose tolerance test (oGTT) and adipocytokine measurements. A comprehensive stepwise selection procedure was performed, followed by c-statistics and integrated discrimination improvement (IDI) analysis. In males, adiponectin levels were significantly lower in the IGT group compared to the non-IGT group (Whitney U test, p ConclusionsIn Chinese individuals without diabetes, no significant evidence for the potential discriminatory value of adiponectin, leptin or their ratio in the identification of IGT on top of conventional risk factors was observed

Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions:a population-based cohort study

<div><p>Background</p><p>Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease.</p><p>Methods and findings</p><p>We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31–26.34) and hypertension (IRR = 1.85; 95% CI 1.59–2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37–5.66), and for cerebrovascular disease 0.95 (95% CI 0.51–1.77; <i>p-</i>value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease.</p><p>Conclusions</p><p>Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.</p></div

All-cause mortality in patients with diabetes under treatment with dapagliflozin:a population-based, open-cohort study in THIN database

Abstract Context: Empagliflozin was found to decrease mortality in patients with type 2 diabetes mellitus (T2DM) and a prior cardiovascular disease (CVD) event. Objectives: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design: General practice, population-based, retrospective cohort study (January 2013 to September 2015). Setting: The Health Improvement Network database. Participants: A total of 22,124 T2DM patients (4444 exposed to dapagliflozin; 17,680 unexposed T2DM patients) matched for age, sex, body mass index, T2DM duration, and smoking. Main Outcome Measures: The primary outcome was all-cause mortality (high and low risk for CVD) in the total study population, expressed as the adjusted incidence rate ratio (aIRR) with 95% confidence intervals (CIs). As a secondary analysis in the low-risk population, all-cause mortality and incident CVD were considered. Results: Patients with T2DM exposed to dapagliflozin were significantly less likely to die of any cause (aIRR: 0.50; 95% CI: 0.33 to 0.75; P = 0.001). Similarly, in low-risk patients, death from any cause was significantly lower in the cohort exposed to dapagliflozin (aIRR: 0.44; 95% CI: 0.25 to 0.78; P = 0.002). The difference in the risk of incident CVD did not reach statistical significance between groups in low-risk patients (aIRR: 0.89; 95% CI: 0.61 to 1.31; P = 0.546). Conclusions: Patients with T2DM who were exposed to dapagliflozin had a lower risk of death from any cause irrespective of baseline CVD status. </jats:sec

Serum testosterone, sex hormone-binding globulin and sex-specific risk of incident type 2 diabetes in a retrospective primary care cohort

__Objective:__ Previous studies suggest that androgens have a sexually dimorphic impact on metabolic dysfunction. However, the sex-specific link between circulating androgens and risk of type 2 diabetes mellitus (T2DM) has not been examined in a large scale, longitudinal cohort, a task we undertook in this study. __Design:__ A retrospective cohort study in a UK primary care database. __Patients:__ We included men and women with available serum testosterone and sex hormone-binding globulin (SHBG) results. __Measurements:__ We categorized serum concentrations according to clinically relevant cut-off points and calculated crude and adjusted T2DM Incidence Rate Ratios (IRRs and aIRRs). __Results:__ Serum testosterone concentrations were available in 70 541 men and 81 889 women; serum SHBG was available in 15 907 men and 42 034 women. In comparison to a reference cohort with serum testosterone ≥20 nmol/L, men with lower serum testosterone had a significantly increased risk of T2DM, with the highest risk in those with serum testosterone <7 nmol/L (aIRR 2.71, 95% CI 2.34-3.14, P < 0.001). In women, the risk of T2DM started to increase significantly when serum testosterone concentrations exceeded 1.5 nmol/L, with the highest risk in women with serum testosterone ≥3.5 nmol/L (aIRR 1.98, 95% CI 1.55-2.52, P < 0.001). These observations were verified in a continuous rather than categorized analysis. The risk of T2DM increased in men and women with serum SHBG <40 and <50 nmol/L, respectively. __Conclusions/Interpretation:__ In this longitudinal study, we found sexually dimorphic associations between serum testosterone and risk of incident T2DM. Androgen deficiency and excess should be considered important risk factors for diabetes in men and women, respectively