The Unlikely Diabetic

I have a patient that is really making me scratch my head. He’s a 45 yo professional. His only medical history is TBI in Iraq in 2006 and subsequent mild hypogonadism. Interestingly he was treated for depression and anxiety (which are known secondary effects of TBI) with various SSRIs, SNRIs, anxiolytics and hypnotics for almost a decade. The patient is an athlete and has a young family and the side effects of those medications were overwhelming so he looked for alternatives. In 2016 he began an anti-inflammatory diet (paleo-type, natural foods, no grains, no sugar, no processed oils, no junk foods with intermittent fasting). He also began an intensive anti-inflammatory supplement regimen with supervision of a TBI specialist which included Clomiphene citrate 50mg q 3 d for hypogonadism, pregnenolone 100 mg, DHEA-S 25mg, Vit D 10,000 iu qd, EPA/DHA supplement). The patient exercises 6 days a week with running, weightlifting, and HIIT. He walks his dog 3 miles every morning.

He receives routine lab work every six months through his TBI specialist to include metabolic profile, CBC, thyroid panel and cholesterol panel. Routine labs are always WNL except for fasting blood sugar of 110-120. A1C 5.3, insulin 13.2.

Concerned for the diabetic range of his blood sugar we began monitoring it more closely. Morning averaged 110-120, postprandial 85-90, post exercise anywhere from 60-99. We started metformin to see if we could bring his fasting blood sugars down. He was titrated to 500mg ER bid. His blood sugar ROSE to fasting 120-125!? Another interesting fact is that his blood sugar doesn’t seem to ever spike. He’s never had a reading above 125 or has had diabetic symptoms. I am perplexed with this patient. He’s doing everything correct, diet, exercise. His insulin levels don’t even indicate insulin resistance. He has a family history of type 2 diabetes.

I’ve read about physiological insulin resistance or glucose sparing for which individuals who eat a low glycemic index/low carb diet can have adaptive insulin resistance. It is the body‘s way of redirecting glucose to the brain and feeding the muscles with ketone bodies. The hallmark of this is slightly elevated fasting blood sugars that are steady without spikes. I’m perplexed as is the patient.

A jaded provider might say that the patient isn’t being forthcoming with his lifestyle habits but this guy is genuine. He’s very proud of the fact that he has overcome his TBI symptoms and improved his quality of life.

Metformin for prevention/delay of type 2 diabetes mellitus (T2DM) and associated complications in persons at increased risk for development of T2DM

Review question
Is the antidiabetic drug metformin able to prevent or delay the development of type 2 diabetes and its associated complications in people with moderately elevated blood sugar levels?

Background
People with moderately elevated blood sugar levels (often referred to as 'prediabetes') are said to have an increased risk for developing diabetes. Metformin is a blood sugar‐lowering medicine which has been used for a long time to treat people with type 2 diabetes. Type 2 diabetes can have bad effects on health in the long term (diabetic complications), such as severe eye or kidney disease or 'diabetic feet', eventually resulting in foot ulcers.

We investigated whether metformin can also be used to prevent or delay type 2 diabetes in people at increased risk. We examined the effects of metformin on patient‐important outcomes, such as complications of diabetes, death from any cause, health‐related quality of life and side effects of the drug.

Study characteristics
To be included, people had to have blood sugar levels higher than normal, but below the levels that are used to diagnose diabetes. We found 20 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with a total of 6774 participants. The comparator group consisted of diet and exercise, intensive diet and exercise or another blood sugar‐lowering drug. One study dominated the evidence (48% of the total number of all participants). Twelve studies were performed in China. We only included studies with a treatment duration of one year or more. The treatment duration in the included studies varied from one to five years.

Key results
Fifteen studies compared metformin against diet and exercise. When compared to standard diet and exercise metformin slightly reduces or delays development of diabetes. However, when compared to intensive diet and exercise, metformin does not provide an additional benefit in reducing or delaying development of diabetes.

In general, the reporting of serious side effects was sparse. Few participants died and we did not detect a clear difference between the intervention and comparator groups. We also did not detect an advantage or disadvantage of metformin in relation to health‐related quality of life. Our included studies did not report on non‐fatal heart attacks, strokes, or complications of diabetes such as kidney or eye disease. Few studies estimated the direct medical costs.

We identified 11 ongoing studies which potentially could provide data for this review. These studies will add a total of 17,853 participants in future updates of our review.