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The synergy between type 2 diabetes mellitus (T2DM) and obesity creates a kind of catch-22 situation: While T2DM is a common adiposopathic and weight reduction can improve glucose metabolism and promote T2DM remission, patients with both these conditions often face obstacles in losing weight.

To shed light on this, Harold E. Bays, MD, of Louisville Metabolic and Atherosclerosis Research Center at the University of Louisville School of Medicine in Kentucky, compiled a comprehensive review based on published evidence. The paper, published in , outlines the multifactorial mechanisms involving the body systems that underlie impaired weight reduction in the face of obesity and T2DM, as well as the genetic, epigenetic, and obesogenic environmental factors thought to mitigate against weight reduction.

In the following interview, Bays, who is also editor-in-chief of Obesity Pillars, also discusses clinical strategies to help overcome barriers to weight loss in individuals with T2DM and obesity.

Is there an estimate of how many people with obesity also have type 2 diabetes mellitus, and vice versa?

Bays: Some estimate that about 30% of patients with obesity have T2DM, and that an estimated 80-90% of people with T2DM have overweight or obesity.

Does T2DM usually hinder weight loss attempts?

Bays: Although figures are lacking, impaired weight reduction with T2DM is a common finding in clinical studies.

What are some of the most common underlying molecular mechanisms of weight loss impairment in individuals with T2DM?

Bays: In most patients with T2DM there are likely multiple reasons T2DM impairs weight reduction:

• When weight reduction improves glucose control, energy is conserved owing to reduced glucose excretion in the urine.

• Especially early in the onset of T2DM, insulin resistance results in hyperinsulinemia. High insulin levels stimulate uptake and storage of fat in fat cells and impair fat breakdown. These obesogenic mechanisms are not found in patients who do not have insulin resistance and high insulin levels.

• Many patients with T2DM are treated with anti-diabetes medications that promote obesity -- for example, insulin, sulfonylureas, meglitinides, and thiazolidinediones.

• Administration of T2DM medications that increase insulin exposure may cause hypoglycemia. Increased caloric intake to avoid or treat low blood sugar may impair weight reduction compared with patients without T2DM who do not require increased caloric consumption to treat or avoid hypoglycemia.

• Diabetes-related abnormalities in several body systems may also contribute to impaired weight reduction. These include endocrine, musculoskeletal, neurological, cardiovasculo-pulmonary, immune, ophthalmologic, nephrologic, dermatologic, and gastrointestinal conditions.

When diabetes contributes to disorders of these systems, the following may be associated with impaired weight reduction:

• People with T2DM are often older, and increasing age impairs weight reduction.

• Some patients may have gender and genetic or epigenetic predispositions to obesity.

• Factors that influence the onset of T2DM include established diabetes meal patterns such as eating three full meals plus an evening snack daily, socioeconomic and psychosocial factors, bias, and discrimination -- all of which are often present in obesity.

• Patients with a disproportionate number of factors that contribute to obesity, as is the case in those with T2DM, would be expected to have greater challenges with weight reduction.

Are most primary care physicians aware of the weight-loss obstacles faced by this patient population?

Bays: Yes, many primary care clinicians have experiences that reflect the difficulty of weight reduction among their patients with T2DM. The intent of this review was to provide the reasons for this common clinical finding.

What are OMA's major recommendations for overcoming this problem?

Bays: One approach to mitigating impaired weight reduction is choosing anti-diabetes medications that increase insulin sensitivity, reduce insulin levels, and decrease body weight -- for example, metformin, glucagon-like peptide-1–based therapies, and sodium glucose-cotransporter 2 inhibitors -- while deprioritizing those that increase insulin exposure and promote weight gain.

What is your main take-home message for physicians to pass along to their patients with obesity and T2DM?

Bays: Even though type 2 diabetes mellitus impairs weight reduction among patients with increased adiposity, clinically meaningful weight reduction improves glucose metabolism and can sometimes promote diabetes remission.

Read the review here and expert commentary about it here.

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