Review for "Predicting Short‐term and Long‐term HbA1c Response after Insulin Initiation in Patients with Type 2 Diabetes Mellitus using Machine Learning"

IntroductionFor people with type 2 diabetes mellitus (T2DM) who require an antidiabetic drug as an add-on to metformin, there is controversy about whether newer drug classes such as dipeptidyl peptidase-4 inhibitors (DPP4i) or sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce the risk of long-term complications compared with sulfonylureas (SU). There is widespread variation across National Health Service Clinical Commissioning Groups (CCGs) in drug choice for second-line treatment in part because National Institute for Health and Care Excellence guidelines do not specify a single preferred drug class, either overall or within specific patient subgroups. This study will evaluate the relative effectiveness of the three most common second-line treatments in the UK (SU, DPP4i and SGLT2i as add-ons to metformin) and help target treatments according to individual risk profiles.Methods and analysisThe study includes people with T2DM prescribed one of the second-line treatments-of-interest between 2014 and 2020 within the UK Clinical Practice Research Datalink linked with Hospital Episode Statistics and Office of National Statistics. We will use an instrumental variable (IV) method to estimate short-term and long-term relative effectiveness of second-line treatments according to individuals’ risk profiles. This method minimises bias from unmeasured confounders by exploiting the natural variation in second-line prescribing across CCGs as an IV for the choice of prescribed treatment. The primary outcome to assess short-term effectiveness will be change in haemoglobin A1c (%) 12 months after treatment initiation. Outcome measures to assess longer-term effectiveness (maximum ~6 years) will include microvascular and macrovascular complications, all-cause mortality and hospital admissions during follow-up.Ethics and disseminationThis study was approved by the Independent Scientific Advisory Committee (20-064) and the London School of Hygiene & Tropical Medicine Research Ethics Committee (21395). Results, codelists and other analysis code will be made available to patients, clinicians, policy-makers and researchers.

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Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Advances in Nutrition ◽

10.1093/advances/nmaa133 ◽

2020 ◽

Author(s):

Thanitsara Rittiphairoj ◽

Krit Pongpirul ◽

Kantima Janchot ◽

Noel T Mueller ◽

Tianjing Li

Keyword(s):

Diabetes Mellitus ◽

Systematic Review ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glycemic Control ◽

Insulin Therapy ◽

P Value ◽

Short Term

ABSTRACT This systematic review aimed to evaluate the effectiveness and safety of probiotics for glycemic control in adults with impaired glucose control, including prediabetes and type 2 diabetes mellitus (T2DM). We searched PubMed, Embase, and Cochrane databases, and trial registries up to February 2019. We included randomized controlled trials (RCTs) of participants with prediabetes or T2DM. Eligible trials compared probiotics versus either placebo, no intervention, or comparison probiotics, or compared synbiotics versus prebiotics. Primary outcomes were mean change in fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) from baseline to short term (<12 wk) and long term (≥12 wk). We performed meta-analyses using the random-effects model. We included 28 RCTs (1947 participants). Overall, probiotics reduced FBG more than the placebo/no intervention group with a mean difference (MD) of –12.99 mg/dL (95% CI: –23.55, –2.42; P value: 0.016) over the short term; and –2.99 mg/dL (95% CI: –5.84, –0.13; P value: 0.040) over the long term. There was also some evidence for reduced HbA1c in the probiotics group at both short term (MD: –0.17; 95% CI: –0.37, 0.02; P value: 0.084) and long term (MD: –0.14; 95% CI: –0.34, 0.06; P value: 0.172), however, these did not reach statistical significance possibly because only a few trials reported HbA1c as an outcome. Subgroup analyses showed a greater reduction in HbA1c in participants not receiving insulin therapy than those receiving insulin therapy. Furthermore, the effect of probiotics on the reduction of FBG was more pronounced in participants with FBG >130 mg/dL and those not receiving insulin therapy than their counterparts. Probiotics were also effective in lowering serum cholesterol over the short and long term. In conclusion, we found that probiotics may have a glucose-lowering effect in T2DM participants. The effect appeared to be stronger in participants with poorly controlled diabetes and those not on insulin therapy. Systematic review registration: CRD42019121682.

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