“You’re wearing an Unna boot – what happened?”

“Doc, my wife made too many tempting desserts while we were in Florida, and when we got back, I had an infected toe. My doctor gave me antibiotics, but the toe turned blue, so they had to amputate.”

I had been treating this man for depression for many years and did not know about his having diabetes, so I asked, “Are you diabetic?”

“No,” he answered. “My doctor says I’ve been prediabetic for 20 years, and he’s put me on a low dose of metformin. … My friends are on twice as much. I don’t even have to have one of those meters.

“I can just go to the senior center or stop by my doctor’s office once a week and have my sugar checked. My wife says she won’t tempt me with any more desserts; she’s buying fruit, which I’m not used to, and I’m not eating bread anymore.

“Hey, those pills you’re giving me for my depression are working great. I am eating and sleeping and doing things I love to do. The wife and I are getting over the kids’ divorces, and we are still able to help out with the grandchild, who has been so sick. When we got back home, I tried to get back with my poker buddies, but one of them is in cardiac rehab; he had a heart attack, and another one, his wife says he’s got Alzheimer’s – he did lose a lot last year and that wasn’t like him. … Yeah, I guess I’m OK. As soon as this toe heals, I’ll be 100%.”

This dialogue is a composite; the names have been changed to protect the innocent, but unfortunately, it is an oft-told tale. The relationship between diabetes and depression has been known for a long time. 1 Each one is a risk factor for the other, and together and separately, they are a risk factor for dementia.

For quite a while, it was thought that having a diabetes diagnosis and having to manage it in and of itself was depressing, and that therefore, people would become depressed. It was also thought that people who are depressed might try to soothe themselves with copious amounts of comfort food and alcohol, and would thereby develop diabetes. Certainly, many people’s routes to depression and diabetes are just that – psychological reactions to having the other disease. But research shows that there is a much deeper physiologic relationship between the two.

Since diabetes and depression or their sequelae are among the 14 leading causes of death in the United States, psychiatrists and other medical professionals need to collaborate in the treatment of these diseases in their patients. Medical homes are good, but most patients continue to receive treatment for all disorders separately and in isolation. If it were not for the medical professional asking directly, or discovering some medication after the patient has given permission for an electronic medication prescribing overview of all his medications, treatment for diabetes or depression might be unknown by the other medical professional. Our noncommunicative EHRs will not help here. The only thing that will help is open communication between the patient and all of his medical treaters.

Now that I am educated and alarmed about the diabetes-depression connection, I send a note to the primary care physician and follow up with a few articles from Science Daily such as “Depression, early death among seniors with diabetes: Strong link found by research,” 2 or “Treating major depression in older adults with diabetes may lower risk of death” 3, or the clincher, “Treatment for diabetes and depression improves both, researchers say.” 4

For patients with type 2 diabetes, the form of the illness usually referred to in research on diabetes and depression, the body becomes insensitive to insulin, i.e., insulin resistance develops. We now know that insulin resistance occurs throughout the body, including the brain. Insulin receptors are present in all organs of the body, including the brain. We also know that the higher fasting glucose level seen in prediabetes is an indication of the development of insulin resistance. Insulin’s job is to get glucose into cells for ready availability of energy and into muscle for backup energy.

If glucose is too plentiful, as it is when sugary foods are overconsumed, insulin directs the rest of the glucose to be stored as fat in the liver, inside blood vessels, around organs, and subcutaneously. Ultimately, there is nowhere else to store the excess energy, and insulin resistance develops. The pancreas, which secretes insulin, keeps on pumping insulin and can poop out, requiring exogenous insulin to keep things moving. 5 Treatments can include insulin itself, medications that increase insulin sensitivity, diet, and exercise to deplete the energy stores, or bariatric surgery, which, by the way, is said to cure both diabetes and depression within 3 weeks after surgery (this effect is negated if patients regain their weight.)

What the research shows

Clinical research from the University of Pennsylvania 6 and Massachusetts General Hospital 7 shows that having a third, nonphysician treater work with patients diagnosed with both disorders improves outcomes. Both of those protocols used cognitive-behavioral therapy (CBT) and motivational interviewing, group treatment, and telephone contact as modalities. One also used electronic monitoring of medication dosing and the record of the glucometer to follow patients’ progress.

In both studies, patients in the protocol groups did better than the treatment-as-usual groups in terms of relief of depression and control of diabetes. In the private primary care physician and psychiatrist office setting, a third party is not practical, but psychiatrists can add motivational interviewing and some aspects of CBT. Also, both psychiatrists and primary care physicians can use electronic medication monitoring and blood glucose monitoring. Recently, Apple released apps that the company said will make it easy for patients with those devices 8, but the old glucometer and pharmacy follow-up for prescriptions also can be useful. Medication (bottle cap) monitors can be expensive and may not be practical for some patients.

A prospective study of 2,525 patients showed that those with depression and metabolic risk factors were more than six times more likely to develop diabetes than patients who had depression alone, metabolic risk factors alone, or neither. These results allow for gross sorting out of which people with depression are more likely to develop diabetes. 9 This can provide an opportunity to intervene before diabetes sets in – and would have saved the toe of the patient I described earlier.

At the cellular level, at least in mice, it appears that insulin resistance in the brain alters dopamine turnover and causes behavioral disorders that look like anxiety and depression. 10 Mice with a brain-specific knockout of the insulin receptor showed “mitochondrial dysfunction and oxidative distress in the dorsal striatum and the nucleus accumbens. Increased levels of MAO A and B leading to increased turnover of dopamine in the mesolimbic system were also observed.”

The depression in these mice was relieved with the use of imipramine and phenelzine, and the researchers also noted that previous research had shown a decrease in depressive-like behavior with the insulin sensitizer rosiglitazone, which reduces glucose in the brain when given to obese, diabetic mice. Certainly, further research is necessary, as is research in humans. But this demonstrates what might be happening to our patients who have metabolic syndrome or diabetes and depression, and may offer suggestions for appropriate treatments.

“If you see something, say something.”

In short, early effective intervention in the metabolic/prediabetes state is best. Taking weights and heights, calculating BMIs, and either measuring or observing waist circumference, can give us a hunch that metabolic syndrome exists. We do our patients a favor if we mention this – and enlist their curiosity and efforts in avoiding or mitigating the ravages of diabetes and worsening depression.

Dr. Harris, a diplomate of the American Board of Obesity Medicine, is in private practice and adult and geriatric psychiatry in Hartford, Conn. She also works as a psychiatric consultant to continuing care retirement organizations and professional groups. Dr. Harris, a former president of the Black Psychiatrists of America, is a Distinguished Fellow of the American Psychiatric Association. Besides psychotherapy, her major clinical interests include geriatrics, and the interface between general medicine and psychiatry.


1. U.S. Medicine, November 2009.

2. Science Daily, March 29, 2014.

3. Science Daily, Jan. 27, 2016.

4. Science Daily, Jan. 18, 2012.

5. “Diabetes Facts and Guidelines,” Yale Diabetes Center, 2011.

6. Ann Fam Med. 2012 Jan-Feb;10(1):15-22.

7. Diabetes Care. 2014;37(3):625-33.

8. Macworld, May 10, 2016.

9. Mol Psychiatry. 2016 Feb 23. doi: 10:1038/mp 2016.7.

10. Proc Natl Acad Sci USA. 2014 Mar 17;112(11):3463-8.


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