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Tag: type 2 diabetes

Muscle Strength: Tied to Type 2 Diabetes Risk

While various studies have linked strength to a lower risk of type 2 diabetes, a new study published in the journal Mayo Clinic Proceedings indicates that even ‘moderate amounts of muscle strength’ were associated with a 32% reduced risk of developing T2DM.

Angelique Brellenthin, a postdoctoral research associate in Iowa State University’s College of Human Sciences and author of the study, stated: “While it’s not entirely clear why higher strength did not protect against diabetes, it’s possible that higher aerobic fitness, higher amounts of physical activity and lower body mass indexes that were present in this higher-strength group were also affecting the relationship between strength and diabetes.”

As published in CNN, this is the first study to explore the relationship between the risk of later development of diabetes and muscular strength: according to the US Centers for Disease Control and Prevention, more than 30 million Americans have diabetes; between 90% to 95% of them have type 2 diabetes. The global number of those diagnosed with diabetes has continued to rise; the World Health Organization has indicated that statistics worldwide have skyrocketed from 108 million in 1980 to 422 million in 2014.

This new study involved 4,681 subjects, 20 and older, who had no type 2 diabetes at the outset of the research. Between the years 1981 and 2006, the adults underwent muscular strength tests and treadmill exercise tests as part of medical examinations at the Cooper Clinic in Dallas. While the strength tests evaluated the upper & lower body using resistance weight machines, the treadmill exercise tests assessed cardiorespiratory fitness. Additionally, the researchers gauged the development of type 2 diabetes: noting that 229 developed the disease. 

The researchers divided the adults’ muscular strength tests into thirds, and found that those in the middle level had a 32% reduced risk of type 2 diabetes compared with the lower third. However, there was no noteworthy association between type 2 diabetes and level of upper muscular strength: compared with the lower level. “While we adjusted for these other healthy factors in the study, it doesn’t completely take away their potential confounding effects, particularly in the higher-strength group,” Brellenthin said. “Future studies will have to consider these to fully understand the relationship between strength and diabetes.” The study had some limitations, including that the sample size was small, and the adults were mostly white and in a middle to upper socioeconomic status. More research is needed to determine whether similar findings would emerge among a more diverse group.

Dr. Monique Tello, a practicing physician at Massachusetts General Hospital and clinical instructor at Harvard Medical School, asserts that the study’s findings point to the importance of both muscle strength and cardiorespiratory fitness for an overall lowered risk of diabetes. “People in the medium strength group tended to also have good cardiorespiratory fitness…there was a good correlation.”

Tello additionally stated that there were people in the low strength group with high cardiorespiratory fitness, and people in the high strength group with low cardiorespiratory fitness. Because “the correlation was not as clear,” some of the more significant findings may have been “washed out.” Previous studies, however, have confirmed that the specific combination of aerobic exercise and resistance training improves blood sugars in people who have diabetes, and can simultaneously act as a preventive measure in the development of diabetes.

Ultimately, Brellenthin said, the most positive and encouraging takeaway from the study is that one does not need to be incredibly strong or muscular to reduce the risk of diabetes. According to the 2018 Physical Activity Guidelines Advisory Committee, adults should perform muscle-strengthening activities on two days each week to stay healthy, and at least 150 minutes of moderate-to-vigorous aerobic activity every week.

“We have a solid body of evidence that shows that just being moderately in good shape—having decent muscle strength and decent cardiorespiratory fitness—is significantly associated with a lower risk of diabetes,” Tello said. “Having both of those things is very good for your health.”

The Role of Real-World Data on the Treatment of T2DM

Type 2 diabetes mellitus (T2DM) is associated with multiple comorbidities, including cardiovascular disease (CVD), hypertension, obesity, dyslipidemia and kidney disease, which increase its morbidity and mortality and complicate treatment decisions.1 Death from CV disease (CVD) is 70% higher in adults with diabetes compared to those without diabetes, and patients with diabetes have a decreased life expectancy, mostly due to premature CV death.  The recent and continuously emerging results from cardiovascular outcomes trials (CVOTs) with the newer antihyperglycemic drugs have shown not only cardiovascular safety, but also CV benefits in addition to non-CV (renal, blood pressure, weight loss) beneficial effects, and are poised to change the clinical management of T2DM and its comorbidities.2  As such, guidelines to individualize T2DM therapy based on patients’ comorbidities have already according to the results from these landmark randomized clinical trials (RCTs).2

However, while RCTs are the gold-standard for evaluating the safety and efficacy of new pharmacotherapies, including for T2DM, the exclusion of many patient populations due to strict criteria in RCTs can sometimes mean that the population studied does not fully represent the patients seen in everyday practice.3  Real-world studies, which use evidence and information from large electronic health and insurance claims databases, may help bridge the gap between randomized trials and actual clinical practice by providing real-world insights to patient care.3  Real-world studies can be either retrospective or prospective, as well as observational or interventional (called prospective pragmatic studies).3  Retrospective real-world studies can include data from several sources (such as those from electronic health records—EHRs, patient registries and claims databases) and can inform or complement the results of RCTs in the real-world setting, as well as a retrospective external control arms for RCTs.3  In addition, large prospective trials with a randomized design that evaluate the efficacy and safety of a therapy in a diverse and heterogenous patient population that is closer to what is seen in clinical practice, are an increasing source or real-world evidence.3

One of the main differences between RCTs and real-world studies is that RCTs are usually conducted in very select patient populations, dictated by the strict inclusion and exclusion criteria determined by the investigators.3  However, due to these stricter criteria, RCTs may lack generalizability, and real-world evidence has the potential to more efficiently provide additional answers that inform outcomes, quality, efficacy and patient care and to fill in the gaps that remain unanswered from RCTs.3  In this setting, real-world studies can provide valuable information on how drugs perform within specific subgroups and patient populations that are often excluded from RCTs and to assess long-term efficacy and safety.3

In fact, several real-world studies have provided key insights that have informed T2D treatment decisions and contributed to the development of clinical practice guidelines.3 A prime example is the UK Diabetes Study which confirmed the importance of glycemic control in the prevention of microvascular and macrovascular complications of T2DM in a real-world population .4 More recently, real-world studies have corroborated some of the evidence from CVOTs.  The CVD-REAL and OBSERVE-4D real-world studies have shown a significant reduction in heart failure hospitalizations with SGLT-2 inhibitors, similar to those observed in RCTs.5,6 In addition, real-world studies with SGLT-2 inhibitors have helped to address some of the safety concerns that have emerged from RCTs, particularly the observed increased risk of lower extremity amputations.  For example, the OBSERVE-4D study showed no increased risk of below-knee extremity (BLKE) amputations with SGLT-2 inhibitors in patients with T2DM compared to other antihyperglycemic agents (including GLP-1 RAs, DPP-4 inhibitors, thiazolidinediones, sulfonylureas, and insulin).6  However, it is important to remember that real-world studies can have several limitations, including being subject to additional bias and confounding factors, which can reduce their internal validity.3  Being up-to-date on landmark RCT results is important, but clinicians should also pay attention to well-designed real-world studies which might help bridge the gap between current literature and everyday patient care.

References:

  1. Baptist, Gallwitz. “The Cardiovascular Benefits Associated with the Use of Sodium-Glucose Cotransporter 2 Inhibitors–Real-World Data.” European Endocrinology1 (2018): 17.
  2. Davies, Melanie J., et al. “Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).” Diabetologia12 (2018): 2461-2498.
  3. Blonde, Lawrence, et al. “Interpretation and Impact of Real-World Clinical Data for the Practicing Clinician.” Advances in therapy(2018): 1-12.
  4. Stratton, Irene M., et al. “Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.” Bmj7258 (2000): 405-412.
  5. Kosiborod, Mikhail, et al. “Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering DrugsClinical Perspective: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors).” Circulation3 (2017): 249-259.
  6. Ryan, Patrick B., et al. “Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non‐SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real‐world meta‐analysis of 4 observational databases (OBSERVE‐4D).” Diabetes, Obesity and Metabolism11 (2018): 2585-2597.