Diabetes

Welcome to another episode of the Integrated Pharmacist Podcast. This is my first in a new series based on disease states rather than a specific modality or product. My goal is look at the major health concerns through the lens of complementary and alternative medicine and find evidence to substantiate that approach to health. I'd like to begin with diabetes.

Diabetes is essentially the body's inability to deal with sugar. Often, the targeted chemical in the body is insulin. Insulin is like the key that unlocks the sugar gate to each of our cells. When it isn't working properly, sugar builds up in our blood where it can cause complications throughout the body. For patients with Type 1 diabetes, their bodies don't make insulin. Most often, this is because their immune system developed a response to the pancreatic cells that produce insulin. In other words, their bodies attack their pancreas to the point that they cannot produce insulin on their own anymore. Because they no longer have the key to let sugar into their cells, they wither and starve to death surrounded by food. Like being stranded at sea, there's water everywhere, but not the kind that is accessible. Injecting insulin is thought to be the only treatment (but not a cure) for Type 1 diabetes. Although some speculate that viral infections and food allergies may contribute to its onset, it is known that Type 1 is genetically inherited.

On the other hand, Type 2 diabetes is characterized by the body's lack of response to insulin. They have the key, but the locks are rusty. As a pharmacist, I've seen drugs targeting type 2 diabetes that basically help the body produce more insulin or get sugar out of the blood in some other way. When those methods stop working, patients begin taking insulin injections to force the sugar doors open. First line treatment taught in standard western medicine is lifestyle modifications. It includes diet and exercise with emphasis on the plate method of eating proportionally appropriate meals.

Type 2 is thought to be caused by diet, obesity, food allergies, viral infection, and stress. The perfect example of how diet and exercise can effect diabetes status is the sad story of the island of Nauru. After several exchanges by political entities, control of the natural resources of the island were officially restored to its inhabitants in 1968. Before this time, the islanders were hard working and subsisted on fish, fruit, and root vegetables with a majority of the diet coming from bananas and yams. Once they had control of their island again, they sold the lucrative resource of phosphate. Everyone on the island became wealthy almost overnight. They no longer had necessity to work hard. Compounding the issue, strip mining had devastated the land making it almost impossible to grow the foods they had thrived on. Their only option was to import highly processed Western foods. Within 40 years, they went from having 0 cases of diabetes to almost half their population. Now that their finite resource has been excavated to exhaustion, they struggle to renew their culture as they strive to deal with the tragic medical burden.

So how do we fix it? The number one go-to for western medicine is metformin. Metformin is a poorly tolerated medication that over time can deplete the body's supply of vitamin B12. Metformin effects multiple pathways in the body, ultimately preventing the liver from releasing sugar into the blood and by making the body more sensitive to insulin. Many patients have stomach upset and digestive issues on this medication. For some people, this intolerance subsides, but I have seen in my short practice those who cannot tolerate this first-line drug. On the other hand, there are scientists who study human longevity that self prescribe this medication. Although there have been no direct studies to date, secondary outcomes of several trials point to the prospect that this medication could extend life. These scientists believe it to be cancer protective, too. As good as this medication is, patients with type 2 diabetes do not suffer from a metformin deficiency. It goes back to the diet.

Several diets have been used to treat type 2 diabetes. There have also been nutritional supplement therapy and ancient herbal remedies. I'd like to address as many of these as I can here. First, the diets. Four major diets come to mind in treating diabetes: complex carbohydrate diet, vegetarian, paleo, and keto.

A 2014 study of gestational diabetes compared a higher complex carbohydrate diet to a high fat diet. The study originated from the idea that the immediate response to gestational diabetes is to simply reduce all carbohydrates. This ultimately leads to an increase in consumed fats which the study founders theorized may not benefit the mother or the fetus long-term. Sixteen women completed the cross over trial and were demonstrated to have controlled blood sugar in both legs of the trial using diet alone. Although the study was not long enough to have a strong measure on long term effects of diabetes, it does demonstrate that blood sugar can be controlled on a complex carbohydrate diet. The size of the trial does make it more difficult to extrapolate to other populations, especially considering this was the narrow group of pregnant females. However, the sample was diverse in its racial profile.

In 2011, another study compared reduced calorie diets - standard vs. vegetarian. Seventy four participants spent 12 weeks on a reduced caloric diet (which is 500 kcal less than a regular diet). After the initial 12 weeks, they were given an exercise program on top of the same diet. All meals were provided for the full 24 week course. 43% of the vegetarian arm vs. 5% in the control arm managed to reduce the amount of medications for diabetes they were taking. The vegetarian group reduced more weight, had better insulin sensitivity, had bigger decreases in visceral and subcutaneous fat, and more dramatic results upon addition of exercise. Unfortunately, the study was not powered to appropriately measure effects on HgbA1c. Another challenge to this trial is that patients on the control diet became less adherent to their diet when exercise was introduced.

For the paleo diet, a study was published in 2009 that demonstrates improved results over the standard diabetes diet. Compared to the diabetes diet, the paleolithic diet included fewer cereals and dairy with increased fruits, vegetables, meats and egg. Again it was a very small study including 13 participants who were given instruction on the two diets. Each participant spent 3 months eating one diet, then crossed over for 3 months on the other diet. Of note, this study allowed participants to eat whatever food they chose after initial education, but they kept food journals that were reported to study investigators. Patients experienced improved hemoglobin A1c, triglycerides, HDL cholesterol, weight and waist circumference while on the paleo diet compared to the standard diabetes diet. Along with the small size of this trial, participants were generally healthier than the average patient with diabetes. Again, this makes it a little more difficult to extrapolate to the general population.

I also found a small trial from 2017 on the ketogenic diet. 34 participants were split between either a ketogenic diet or a moderate-carbohydrate, low fat, calorie-restricted diet. The study ran for a full year. During the first few weeks, participants in both groups were coached in their specific diets. Those in the keto arm were instructed to aim for ketone blood levels of 0.5 to 3 mmol which were checked twice a week during the first 6 weeks. The participants in the calorie-restricted arm were coached on how to choose foods within their designated limits which includes the typical 500 kcal deficit compared to their calculated maintenance amounts. After the initial 6 weeks, both groups were instructed on proper exercise, sleep, and mindfulness. By the end of the trial, the keto diet outperformed the moderate diet in lowering HgA1c, weight reduction, and reduction of medications for controlling diabetes. As with the other studies, patients were excluded if they were insulin dependent or on more than 3 diabetes medications. Interestingly, the study investigators could not determine how influential the mindfulness portion of the trial effected the results, and they hoped to further explore that idea in the future.

Although these trials were small, they do tell an interesting story about diet for patients dealing with diabetes. We know that diet control can have a positive effect on health. We also know that standard low-calorie diets have been difficult to follow long-term. The big picture that gets painted in my mind is that having a general restriction of calories has less of an effect than some of these other diets. The thing I noticed that is similar among all these different diets is the general increase in vegetables and avoidance of processed foods. Whether you're trying to avoid meats, carbohydrates, or foods unavailable to cavemen, it's difficult to justify many of the processed foods that we generally know to have less nutritional value. What does seem clear is that sticking to some diet has a positive effect on diabetes status, but caution must be taken in patients whose diabetes is more developed. Because participants in all these studies were generally younger and healthier, it is unclear what effect these diets would have on older, sicker patients.

Several vitamins and supplements have been proposed in the reversal of diabetic symptoms including Vitamins E, C, and several B vitamins, chromium, magnesium, potassium, zinc, CoQ10, and amino acids. I covered CoQ10 in a previous podcast for patients with diabetes.

I found a meta-analysis for chromium that found evidence for its use. The review included 25 trials and came to the conclusion that chromium can have a positive effect on HbA1c and fasting plasma glucose. Chromium mono-therapy also improved triglycerides and HDL cholesterol levels. The most common dose was 200 micrograms daily, and did not increase side effects experienced by participants compared to the placebo groups at that dose. Upon scrutiny, the biggest effects for chromium were among patients with HbA1c above 8.0% and particularly among those patients with poor diet and exercise who were likely already low in chromium. The supplements that showed the most benefit were chromium picolinate and brewers yeast both of which are formulated for optimal absorption. However it was determined that stronger trials are needed both in size and length to solidify these results.

There is a double-blind, placebo-controlled trial for zinc in overweight patients with type 2 diabetes published last year including 70 patients. Participants were given 50 mg zinc gluconate as 25 mg twice daily or matching placebo. After the course of 8 weeks, the study arm showed benefits in HbA1c, fasting blood glucose, triglycerides, and total cholesterol. I should also note that the study was specifically built to detect gene expression that effects insulin and obesity. I also find it interesting that the study was only run for 8 weeks with an outcome of HbA1c. Because A1c represents a 3 month window of blood glucose, the change would have to be significant to be a measurable difference in less than 3 months.

Unfortunately, I was unable to find much supporting evidence for any other supplement.

However, there is plenty of evidence that suggests exercise and stress management can have a significant effect on diabetes. As an example, I found a meta-analysis that looked at the use of yoga. I chose this analysis because it can act as both exercise and stress reduction. The meta-analysis included 23 studies with a total of 2473 participants who were on average 53 years old and slightly more male than female. The report suggested that the studies they analyzed that included meditation and breathing had greater reductions in blood glucose readings.

For herbal remedies, fenugreek, berberine, cinnamon and olive held up to scrutiny. A meta-analysis of 12 studies looking at fenugreek's ability to lower fasting blood glucose and total cholesterol with the most significant drop in HbA1c at an average of 1.16%. Of the 1173 participants included in the analysis, no serious side effects were reported; however, some patients did report stomach upset. The median dose of fenugreek was 6.3 grams per day with a range of 1 to 100 grams. The median length of study was 60 days with a range of 1 week to 3 years.

In China published in 2009, an odd study looked to demonstrate the efficacy of berberine in patients with diabetes. I say that it is odd, because it had two different legs. One group included 36 patients which were randomly selected to take 500mg berberine three times a day with meals or 500mg Metformin three times a day after meals. The other leg included 48 participants who added 500mg berberine to whatever diabetes therapy they were already taking. The first group demonstrated equivalent efficacy of berberine to metformin in managing blood sugar and even outperformed metformin in managing triglycerides and total cholesterol. The second group demonstrated additive effects to concurrent diabetes medications. Patients otherwise stable on their medications tended to drop weight and waist circumference. Some patients did complain of GI upset; however, this effect (like for metformin) usually subsided within 4 weeks.

I found a randomized, placebo controlled study from England that demonstrates the power of cinnamon. Participants were included if they had at least one medication for diabetes and remained uncontrolled as defined by HbA1c > 8%. 58 participants took either 2 grams of cinnamon or matching placebo for 12 weeks. They made no other changes to medications or diet. I think that was an interesting choice, because it would drive clinicians to add cinnamon rather than replace an existing intervention. The most significant findings were in lowering HbA1c and blood pressure. No side effects were reported. Although participants were more diverse than previous studies, the investigators could have stratified the participants better across age, gender, diabetes medication, and time from diagnosis. It looks as though they did not use a standardized method for developing the cinnamon supplement which also effects how we can interpret the results.

Another meta-analysis comprising over 15,000 cases in four cohort studies looked at using olive oil as a food to treat and prevent type 2 diabetes. The analysis found a nonlinear effect between consuming olive oil and diabetes control. The most significant findings were among HbA1c and fasting plasma glucose in patients with diabetes who consumed olive oil. The maximum risk reduction stood at about 13% when patients consumed 15-20 grams per day. However, it was unclear if these findings were completely due to the consumption of olive oil or if the findings were due to the full Mediterranean diet of which olive oil is a major component.

The last set of treatments I wanted to look into is Ayurvedic and Traditional Chinese Medicines. The body of evidence is growing for both of these fields and it looks promising. However, I did not have access to the trials I was hoping to include in this production.

To wrap things up, it appears that diabetes can be managed through a number of means accessible to most patients. Switching to a diet that is rich in vegetables and low in processed foods seems to be a significant factor in managing blood sugars. Even small changes in diet for the better can make an impact. Fenugreek, berberine, cinnamon, and olive oil are easy additions to diet that can also have a significant effect. It's also important that patients with diabetes keep their vitamins and minerals at appropriate levels. Zinc and chromium specifically can have a direct effect on diabetes. Although not established in this episode, medications can deplete other vitamins such as the B vitamins which can play an important role in controlling blood sugar. This can be supported by lifestyle changes that include increased exercise and stress-releasing activities.

I have been able to find good quality zinc and chromium supplements that I trust for less than $20 per 90 day supply. Fenugreek, cinnamon and olive oil can be bought as both a food and a supplement at reasonable prices as well. Berberine can be as much as $50 for a 90 day supply which is still less than $1 per dose.

I know gaining control over diabetes can be a real struggle for patients. Despite hard effort, some patients really do not achieve significant outcomes. Knowing how powerful western medicine can be for this disease could make it easy to rely on those medications. I'm sure for a lot of patients, they justify not making these lifestyle changes because of how powerful those medications are. However, it might be useful to educate these patients that the best outcomes still occur only when added to diet and lifestyle changes. I know it's important to help patients overcome the barriers that prevent them from making these changes. The best part is most of these interventions are free or marginally more expensive than their current lifestyle. When considering the long term medical expenses averted, it's a small price to pay.

I want to thank you for joining me today. It's exciting to me to discover the myriad of options patients have for taking care of their health. I hope you enjoyed this presentation on diabetes and I hope you were able to take something useful that you can pass on to your own patients. If you know of someone who would benefit from listening to this podcast, please share it with them. It also helps this podcast to grow when you rate and review it! We'll see you next time on the integrated pharmacist podcast.

References:

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Kahleova H, Matoulek M, Malinska H, et al. Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes. Diabet Med. 2011;28(5):549-559. doi:10.1111/j.1464-5491.2010.03209.x

Jönsson T, Granfeldt Y, Ahrén B, et al. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol. 2009;8:35. Published 2009 Jul 16. doi:10.1186/1475-2840-8-35

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