Ph. Abbas – Page 6 – KNOW & TREAT UTI

Hypoglycemia is a medical emergency that may be life-threatening if not managed promptly. It is commonly found among diabetic patients as a complication of mismanagement. But what about UTI? Is there any chance to develop hypoglycemia during UTI? Or, does hypoglycemia contributes to UTI? Let us discuss the topics in brief. Does UTI lead to hypoglycemia? Hypoglycemia or low blood sugar level is not considered a typical manifestation of urinary tract infection. It is very rarely reported by UTI patients. Let’s discuss the possibilities where UTI patients may suffer from hypoglycemia. First of all, hypoglycemia may be rarely caused by severe and complicated UTI. If you are suffering from complicated upper urinary tract infections like pyelonephritis, it may spread to blood leading to sepsis. If acute pyelonephritis is left untreated, especially in debilitated and immunosuppressed patients, the bacteria may enter the bloodstream. The bacteria multiply in the blood, release toxins, and lead to a widespread immune reaction. The complex event is termed sepsis. Rarely, sepsis patients develop hypoglycemia as a complication. The mechanism(s) for hypoglycemia with sepsis is not well defined. Depleted glycogen stores, impaired gluconeogenesis (glucose synthesis) and increased peripheral glucose utilization may all be contributing factors. Secondly, urinary tract infection is common in diabetic patients. And hypoglycemia is a common complication of inappropriate blood sugar control. Especially old debilitated patients often fail to maintain the dosages schedule of insulin and other drugs. Infections like UTI often induce anorexia (loss of appetite) and nausea which is more prominent in old age. So they don’t take their meals timely and adequately. And now they will have to take additional drugs for UTI. Without proper supervision, they often fail to take all drugs timely. Reduced food intake along with inappropriate drug intake increases the risk of developing hypoglycemia. So, diabetic patients with UTI may present with hypoglycemia in the hospital. Thirdly, drug interaction may be an important cause of hypoglycemia. Antibiotics are the mainstay of UTI management. But, some antibiotics may lead to hypoglycemia. This is commonly seen in type-2 diabetic patients who are taking oral anti-diabetic drugs. Fluoroquinolones, clarithromycin, linezolid, tigecycline, cefditoren, doxycycline, and trimethoprim-sulfamethoxazole are known to be associated with hypoglycemia. Study shows that fluoroquinolones like ciprofloxacin and levofloxacin may interact with blood sugar-lowering agents like sulfonylureas and meglitinides leading to hypoglycemia. And these antibiotics are very commonly used in UTI. We are going to discuss it more in the latter part of this article. Does hypoglycemia lead to UTI? Curious patients often ask this question. Hyperglycemia is known to facilitate infections like a UTI. So, they wonder if hypoglycemia can do the same or not. What do you think? Is that possible? Think a little. You will get the answer if you just have some basic idea of UTI and blood sugar. You must have acquired some idea from other articles on our site. At first, think of hypoglycemia. We call it hypoglycemia when the blood sugar level falls below 3.5 mmol/l. If you are diabetic or have a close relative with diabetes mellitus, you must have some idea. Hypoglycemia is e medical emergency. Symptoms of hypoglycemia deteriorate rapidly if not treated. You may develop convulsions or even get unconscious. If untreated, it may endanger your life. So, the hypoglycemia will not last for a longer period, unlike hyperglycemia. Either you will get treated or it will endanger your life. Fortunately, it responds rapidly to treatment. As you know, just even taking some sugar will raise the blood glucose level promptly. In this short period, hypoglycemic status has no chance to facilitate other infectious diseases like a urinary tract infection. However, hypoglycemia may cause brain damage and worsen any neurological diseases if present. But no evidence was found to support its relationship with UTI. The only possibility is if you require urinary catheterization during a hypoglycemic coma. But thinking of such events is too far from the expected reality. Hope you got the answer. How the blood sugar level interacts with a UTI? As per the above discussion, you must have gotten an idea of the relationship between blood sugar levels and UTI. Let us discuss this a bit more in this section. First of all, an acute increase in blood sugar level have no immediate effect on UTI, But the persistent rise of blood sugar levels has widespread effects on body physiology, which may increase the risk of many other illnesses including UTI. Hyperglycemia in diabetes may affect every system of your body starting from skin to brain. We will talk about UTI only. In diabetes mellitus, there is an increased level of sugar in the blood. But the cells of your body can’t use it due to the lack of insulin. So, the cells are deprived of energy and protein synthesis is impaired. The protective antibodies and other immune mediators of our body are also proteins. So, the immunity of our body is reduced making us prone to infections like UTI. Moreover, hyperglycemia leads to increased excretion of glucose in urine. Thus the urine becomes a more favorable medium for bacterial growth. That’s why diabetic patients suffer from recurrent UTI. And due to suppressed immunity, the infection spreads rapidly leading to complicated UTI. Please note an important point here. Unlike urine, blood is a very good medium for the growth of microorganisms, possibly the best one. Increased blood sugar level has nothing to do to make it more favorable as a growth medium. It just impairs the immunity so that your body can’t kill the bacteria and the infection spreads. So, we can say that increased blood sugar levels increase the risk of recurrent and severe urinary tract infections. Now, how the urinary tract infection affects the blood sugar level. The answer is not straightforward. It depends on the severity of infection, immune response, and coexisting illnesses. The general rule for an immunocompetent body is that any infection will induce a stress response in the body. During any illness or infection including UTI, your body will secrete steroid hormones. Along with many other effects, steroids increase glucose synthesis leading to hyperglycemia. It happens even if you don’t take much food. This is a protective mechanism for the body to supply enough energy to fight the infection. However, this rise of blood sugar level due to UTI will not go to pathological level unless you are diabetic. And it subsides as soon as the infection is cured. So, nothing to worry about. On the other hand, complicated UTI in immunocompromised patients may lead to sepsis, And as we have discussed earlier, it may cause hypoglycemia in some cases. Do oral hypoglycemic drugs affect UTI? Yes, some of the oral anti-diabetic or hypoglycemic drugs are reported to increase the risk of urinary tract infection. Especially the post-marketing surveillance of some newer hypoglycemic drugs showed an increased incidence of infection. Three classes of medications used in the treatment of diabetes have been implicated in an increased risk of infections: glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Among those, SGLT2 inhibitors like canagliflozin (Invokana ), Dapagliflozin (Forxiga ), empagliflozin (Jardiance), etc are most notorious for increasing the risk of UTI. As glucose is an essential nutrient for our life and hypoglycemia is life-threatening, our body always tries to reduce glucose excretion from the body. In our kidneys, glucose is also filtrated like other constituents from blood. Then it is reabsorbed again from the kidney by a transporter called SGLT2. But during diabetes mellitus, persistent high blood sugar becomes harmful for us. So, increasing glucose excretion using a drug may be a good way to reduce blood glucose levels. That’s what these drugs do to control hyperglycemia. They inhibit the SGLT2 transporter in the kidney and increase glucose excretion via urine. So, if you take any of these drugs, there will be an increased glucose level in your urine (termed glycosuria). But the negative side is glycosuria increases the risk of developing urinary tract infections. A systematic review of SGLT2 inhibitors (seven trials) found that compared with the control groups, there was an increased rate of UTIs. It also increases the risk of other urogenital infections like vaginal candidiasis. These infections are usually mild to moderate and don’t require discontinuing the drug, and the frequency of infection gradually reduces after six months of initiation. But you should be aware of the symptoms of UTI and take the treatment if required. The members of the GLP-1 RA antidiabetic drugs like exenatide (Byetta), liraglutide (Saxenda), dulaglutide (Trulicity ), lixisenatide (Lyxumia), semaglutide (Ozempic), etc are also reported to cause UTI. But the incidence is lower compared to SGLT2 inhibitors. And the drugs of DPP-4 inhibitors like sitagliptin (Januvia), Saxagliptin (Onglyza), linagliptin (Tradjenta) are found to be associated with a higher risk of upper respiratory tract infection, but not with UTI. Do drugs used in UTI cause hypoglycemia? If we think of the drugs used in UTI management, antibiotics come first. As we have already discussed fluoroquinolone antibiotics like ciprofloxacin and levofloxacin may cause hypoglycemia if taken with antidiabetic drugs. One of the fluoroquinolones named gatifloxacin is notorious for causing hypoglycemia. Luckily we don’t use it commonly for UTI. In 2018, an internal safety review by the Food and Drug Administration found 67 cases of life-threatening hypoglycemia caused by fluoroquinolones. Among these 67 cases, 44 were due to levofloxacin. FDA warns that older diabetic patients who take insulin or oral antidiabetic drugs should be closely monitored when taking fluoroquinolones. Regular blood sugar monitoring and patient education are essential to avoid a hypoglycemic attack. Among other antibiotics, cotrimoxazole is often used for UTI in many countries which may induce hypoglycemia. However, in non-diabetic patients, the hypoglycemic effect of these antibiotics is usually mild and no complications arise. So, don’t panic if your doctor prescribes any of those. Other drugs used in UTI include antispasmodics (e.g. Timonium), painkillers (e.g. paracetamol, naproxen, ketorolac, etc), urine alkalinizing agents (e.g. potassium citrates), etc. These drugs have no known relationship with hypoglycemia. To conclude We can say that there is nothing to be worried about, about the impact of hypoglycemia on UTI unless you are diabetic. But if you have diabetes mellitus and suffering from UTI, talk to the doctor about your diabetes and drug history. He will do the needful to avoid any complications and also read our Vitamins for UTI article, which will help you know how to prevent UTIs in the first place. That’s all for now. Thanks for reading with patience.