Optimizing Metabolism

by Ingrid Kohlstadt MD, MPH, FACN, FACPM

Cancer and Insulin Resistance:

Evidence Demanding Action

Introduction

When it comes to obesity, there are a lot of opinions. The news media tend to make news by highlighting disagreements. Consensus should be publicized, too! For example, experts agree that a 5% to 10% reduction in weight improves overall health among obese and overweight individuals. Even though key opinion leaders may not agree on what weight-loss strategies are the most effective, they do agree that combining proven strategies for weight reduction increases the likelihood of meaningful, sustained weight loss.

This month’s Townsend Letter, focused on cancer treatments, addresses another convergence: the cancer-obesity-insulin connection. As I learned from authors of Advancing Medicine with Food and Nutrients expert on this topic, I was compelled by the supporting science. The cancer and insulin-resistance connection is supported by robust data including epidemiology, basic science, and clinical trials. Here the science is applied to clinical practice.

The Cancer and Insulin Link

Excess body fat impairs insulin uptake and leads to insulin resistance. Insulin resistance (IR) in turn sets the metabolic stage for various cancers to occur or recur.

IR predicts adverse prognosis. It increases mortality rates in many cancer types, including breast, prostate, colorectal, kidney, pancreas, liver, esophageal, gallbladder, endometrial, cervical, ovarian, myeloma, non-Hodgkin’s lymphoma, and leukemia. Even though excess weight does not increase the risk of developing premenopausal breast cancer and prostate cancer, risk of recurrence and cancer mortality correlates with increasing body mass index for both pre- and postmenopausal breast cancer as well as prostate cancer.

Some cancer treatments contribute to insulin resistance. Cancer treatment may increase the incline on the uphill challenge of diet and exercise in various ways such as medication-induced nutrient deficiencies, reduced exercise tolerance, or limited capacity to prepare healthful foods. There are two specific areas where cancer treatment and insulin resistance are strongly associated:

Use of high-dose steroids in chemotherapy.

Patients receiving chemotherapy that is associated with nausea and emesis are pretreated with ondansetron (Zofran). Often dexamethasone is added to ondansetron to potentiate antiemetic effects. Dexamethasone is a steroid medication more potent than prednisone, and steroid medications promote weight gain, muscle loss, and insulin resistance.

Sarcopenia.

Loss of muscle is associated with insulin resistance. Cancer therapies which reduce testosterone are particularly noted for reducing muscle mass. Other cancer therapies that alter sex hormone levels or are pro-inflammatory disturb the metabolic underpinnings of muscle. Muscle loss is a harbinger of fat gain.

Patient History

The usefulness of a patient history depends to some extent on what a patient is willing to share. When asking cancer survivors about their weight and insulin sensitivity, there are several ways to build the needed trust.

If someone has survived cancer – a rough journey indeed – that person certainly doesn’t lack the willpower to diet and exercise a few pounds away. Acknowledging this determination is certainly merited and can open the conversation in a supportive way. Also point out that the cancer treatment itself is likely to have made weight maintenance more difficult.

Additionally, the subtle cues of an office environment will shape the history-taking even before the practitioner meets the patient. Some practitioners check their office environment as follows:

• chairs accommodate patients with weight issues;

• office scales are discretely placed;

• large exam gowns are provided;

• large size blood pressure cuffs are used when needed;

• staff uses neutral words such as weight issue or excess weight.

Questions to establish baseline parameters and guide discussions about diet, weight loss, and improving sensitivity to insulin include:

What do you eat for breakfast?

Eating breakfast improves metabolic rate. Patients who skip breakfast miss out on boosting their metabolic rate and may have underlying insulin resistance and elevated triglycerides. Food selection at breakfast can prevent or promote food cravings throughout the day.

How is your digestion?

Irregular bowel patterns, heartburn, and constipation influence food selection. Impaired digestion can point to gallbladder disease; use of artificial sweeteners; food allergies or intolerances; and an opportunity to increase fiber, magnesium, vitamin C, and hydration.

What has helped you lose weight in the past (if

you

have tried)?

Diet patterns, nutritional programs, supplements, prescription medications, surgeries, and fitness programs that have been helpful in the past are likely to be helpful again as the patient’s metabolism is optimized. Nonmedically advised weight loss, eating disorders, depressed mood, and risks for muscle atrophy might also be identified.

Physical Exam

Cancer survivors have journeyed through extensive medical testing. Not all, however, may have had a recent check-up evaluating potential contributors to insulin resistance. A measuring tape, an alcohol swab, a tongue depressor, and thumb pressure used by skilled clinicians can identify modifiable conditions, which, when corrected, can help patients towards insulin sensitivity.

Monitoring fat and muscle mass

: Reduction in adipose tissue can be estimated by monitoring waist circumference, waist to hip ratio, bioimpedence (BIA), and resting metabolic rate. Clinical assessment can be supported by imaging studies such as dual-energy X-ray absorptiometry. DEXA technically assesses bone densitometry and body composition, although not all facilities utilize this feature. Obesity and muscle atrophy coexist in a condition known as sarcopenic obesity, which predicts mortality and often responds to treatment.

Neck circumference

: Neck circumference is a predictor of sleep apnea and its severity. Since obstructive sleep apnea is obesogenic, treatment with positive airway pressure should not be delayed due to intended weight reduction, but used in conjunction.

First cranial nerve (CNI) assessment

: CNI impairment can be diagnosed and quantified using the alcohol sniff test. An alcohol swab is held 40 cm from the patient’s nose and moved progressively forward until the patient can detect the smell. Making patients aware of their deficit in olfaction and taste can help them avoid inadvertent oversweetening or oversalting of food.

Oral cavity

: Xerostomia, periodontal disease, tooth decay, amalgam fillings, and odor may indicate barriers to weight reduction, including dehydration, unfavorable microbiota, inadequate mastication, undermethylation and insulin resistance.

Hydration status

: Dry mucus membranes, pedal edema, poor skin turgor, and a dry mouth generally indicate intracellular dehydration, and can be corroborated with urine specific gravity. Since muscle is more hydrous than fat and therefore conducts a current more quickly, poor hydration is associated with less favorable BIA.

Moderate pressure to shinbones

: Applying moderate pressure to an adult patient’s shinbones or ribs is associated with discomfort when osteomalacia is present. Osteomalacia is a late but not rare manifestation of vitamin D deficiency, and obesity elevates risk. Clinical findings should be corroborated with laboratory testing and treated. Even moderately low vitamin D levels forestall weight loss by perpetuating insulin resistance, possibly lowering mood, and limiting physical activity.

Laboratory Tests

While a number of tests may be indicated, a calculated clinical measure of insulin resistance can serve as a baseline measure for comparison and a measure of treatment responsiveness. The homeostasis model assessment (HOMA) is calculated from a single measure of fasting glucose and insulin, as follows:

HOMA = [insulin (pg/ml) × glucose (mg/dl)] /405.

Clinical Interventions

When a patient is overweight, reducing weight to an optimal range improves insulin response. That said, an important point to emphasize is that reducing insulin resistance, even before it becomes associated with excess body weight, is a meaningful clinical intervention for reducing risk of cancer recurrence.

When other indications for use are present, the prescription medication metformin is effectively insulin sensitizing among cancer survivors. Metformin is a biguanide, a class of medications that acts by decreasing glucose production and improving liver sensitivity to insulin. One correctable effect is that metformin depletes vitamin B12. Metformin is a plant extract. It is derived from French lilac, and the exact mechanism remains to be worked out. This clinical detail tips the hat, to suggest that other phytonutrients may be insulin sensitizing.

Several phytonutrients sourced from food and supplements reduce IR:

• Cinnamon

  is insulin sensitizing. Recommending cinnamon is not an endorsement of breakfast cereals, toast, hot chocolate, cookies, and sticky buns; however, incorporating cinnamon into cooking oil, apple sauce, yogurt, or coffee is encouraged for its insulin-sensitizing effect. Additionally, the flavor reduces the need for sugar as perceived by some palates.

• Berberine

  is found in the stems and roots of various plants, most notably the barberry, and is used as a source of natural yellow dye. It improves insulin sensitivity and reduces the growth of some cancers. It is also used in cancer care to reduce adverse effects of radiation. Supplemental dosing varies based on the indication for use.

• Resveratrol

  may sensitize to insulin by a slight but clinically measurable reduction in appetite. It inhibits cancer across mechanisms. One of the important findings emerging about red wine is that a small and consistent amount of resveratrol may be beneficial, as appears to be the case with phytonutrients more broadly.

• Curcumin

  is a phytonutrient that reduces the inflammation associated with weight reduction. As such it may also improve insulin sensitivity. Curcumin is found in curry spices and can be initiated at a dose of 400 mg per day with food.

Bioactive phytonutrients tend to be fat soluble and are therefore found in the fatty components of food. Cooking with minimally processed oils and spices and eating whole-foods sources of plant fats such as nuts and seeds increase dietary phytonutrient intake.

Summary

Improving sensitivity to insulin is effective and scientifically supported for cancer prevention. Treatment includes addressing opportunities for change as noted in the patient history, identifying and treating physical exam findings, and emphasizing insulin sensitizing food and nutrients even when a cancer survivor is not overweight.

Ingrid Kohlstadt, MD, MPH, FACN, FACPM, is the founder of INGRIDients Inc., where she has edited Advancing Medicine with Food and Nutrients, 2nd edition (CRC Press; December 2012). On the faculty of Johns Hopkins Bloomberg School of Public Health, Dr. Kohlstadt is researching an approach to leverage nutrition more fully in disease prevention.