Dr Edelman on Hypoglycemia Unawareness & Glucagon

Diabetes Daily has in important interview with Dr Steven Edelman on hypoglycemia (particularly in type 1 diabetes) and the need for injectable glucacon to treat it. This could easily apply also to type 2 diabetes that’s treated with insulin or other drugs that can cause hypoglycemia. Folks with type 1 diabetes seem to be more prone to hypoglycemia unawareness. That is, the blood sugar is dangerously low, but not recognized or treated promptly, potentially resulting death. Dr Edelman notes that dangerous hypoglycemia has been significantly reduced by the use of continuous glucose monitoring (CGM).

Note that CGM measure glucose levels in the the fluid in between the cells of subcutaneous tissue (AKA interstitial fluid). Your familiar fingerstick glucose is measuring capillary fluid levels. Capillaries are tiny blood vessels at the end of arteries. After going through the capillaries, blood enters veins for the return trip to the lung and heart. Glucose levels in the interstitial fluid and capillaries may not be the same as in the large arteries delivering glucose to the brain. Most CGM devices will provide the user with an alert when the glucose level drops too low, so that remedial action can be taken.

An excerpt from Diabetes Daily:

What are some ways that the CGM can most effectively help avoid hypos?

Well, one of the things I do in clinic is to really check where people set their upper and lower alerts. I had a patient yesterday in clinic who has had type 1 for 60 years. Her A1C is unbelievable, but she does have hypo unawareness and her lower alert was 65. You have to convince people that the extra alerts are worth it to you.

A lot of people said they put their lower alert at 65 and they don’t realize this situation called the “lag time.” So, when your blood sugar is dropping, even if you have a diagonal arrow down compared to, even worse, one arrow down or two arrows down, looking at the Dexcom arrows, they don’t realize that the glucose in your circulation is probably much lower than it appears on the Dexcom monitor or your phone. Because the Dexcom sensor and other sensors too, they measure the glucose in the subcutaneous tissue, and there’s a lag between the subcutaneous tissue and the circulation.

When your Dexcom goes off or when your CGM goes off at 65, and if your trend arrow’s going down, you could be 45 or 40. So that’s really an important issue, especially for people that their symptoms aren’t as obvious anymore. You could be caught off guard. And I had multiple patients that has occurred with. And then unfortunately, as you know, the majority of T1Ds in this country do not wear a CGM and that’s the topic of a whole other story.

Does this lag time issue apply to a regular glucometer as well?

Yes. If your blood sugar is dropping, your meter or CGM may be perfectly accurate of the subcutaneous tissue at 65. If you checked your blood sugar with a meter, it’s still going to say 65, but your circulation that’s going to your brain might be 45. So, the lag time is key. You could have the most accurate meter or CGM in the world, it doesn’t affect the lag time.


Click for my five-year-old article on drugs that can cause diabetes.

Click for my brief article on hypoglycemia unawareness.

Click for my general article on recognition and treatment of hypoglycemia.

Steve Parker, M.D.

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Finerenon: New Hope for Prevention of Kidney Disease and Cardiac Death in Type 2 Diabetes

Your friendly neighborhood drug supplier

Verbatim from the FDA press release:

FDA has approved Kerendia (finerenone) tablets to reduce the risk of kidney function decline, kidney failure, cardiovascular death, non-fatal heart attacks, and hospitalization for heart failure in adults with chronic kidney disease associated with type 2 diabetes.

Diabetes is the leading cause of chronic kidney disease and kidney failure in the United States. Chronic kidney disease occurs when the kidneys are damaged and cannot filter blood normally. Because of defective filtering, patients can have complications related to fluid, electrolytes (minerals required for many bodily processes), and waste build-up in the body. Chronic kidney disease sometimes can progress to kidney failure. Patients also are at high risk of heart disease.

The ultimate role of finerenone in our armamentarium against disease and suffering will probably depend on cost and the number needed to treat.

The efficacy of Kerendia to improve kidney and heart outcomes was evaluated in a randomized, multicenter, double-blind, placebo-controlled study in adults with chronic kidney disease associated with type 2 diabetes. In this study, 5,674 patients were randomly assigned to receive either Kerendia or a placebo.

The study compared the two groups for the number of patients whose disease progressed to a composite (or combined) endpoint that included at least a 40% reduction in kidney function, progression to kidney failure, or kidney death. Results showed that 504 of the 2,833 patients who received Kerendia had at least one of the events in the composite endpoint compared to 600 of the 2,841 patients who received a placebo.

The study also compared the two groups for the number of patients who experienced cardiovascular death, a non-fatal heart attack, non-fatal stroke, or hospitalization for heart failure. Results showed that 367 of the 2,833 patients receiving Kerendia had at least one of the events in the composite endpoint compared to 420 of the 2,841 patients who received a placebo, with the treatment showing a reduction in the risk of cardiovascular death, non-fatal heart attack, and hospitalization for heart failure.

Side effects of Kerendia include hyperkalemia (high levels of potassium), hypotension (low blood pressure), and hyponatremia (low levels of sodium). Patients with adrenal insufficiency (when the body does not produce enough of certain hormones) and those receiving simultaneous treatment with strong CYP3A4 inhibitors should not take Kerendia.

Kerendia received priority review and fast track designations for this application.

FDA granted the approval of Kerendia to Bayer Healthcare.


Click for prescribing information.


Parker here.

Just offhand, finerenone doesn’t look like a great drug. Helpful, maybe. Chronic kidney disease can end up at ESRD (end stage renal disease), which requires thrice weekly hemodialysis if the patient wants to stay alive. (Yes, peritoneal dialysis is an alternative.) Preventing ESRD is an incredible benefit for an individual.

Finerenone seems to be a well-tolerated daily pill. The main adverse effect is elevated blood potassium level, which can cause palpitations, and death infrequently. Less commonly, the drug can cause low blood pressure.

Steve Parker, M.D.

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My Recent Posts About COVID-19

Artist’s rendition of coronavirus

I write about COVID-19 at one of my other super-secret blogs. If you’re interested:

Steve Parker, M.D.

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QOTD: Men and Women…Together

dementia, memory loss, Mediterranean diet, low-carb diet, glycemic index, dementia memory loss
“Yes, the kids are long gone, but we’re still together.”

Men offer women what other women can’t, and when they do it right, everyone is better off. Women at their best bring out the best in men. They — men, that is — are more inclined to behave themselves, to work harder, scrape off their rougher edges, and be more dependable. This extends into other arenas of social life, like being a good father, a reliable worker, and a helpful neighbor. Women get to have men around to be “the fathers” to the children that they cannot be, to share the burdens and joys of child-rearing, and, together, ease the chastening of old age.

-Stephen Paul Foster, July 1, 2021 (I’d link to the source but the website owner has blocked my IP address)

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Does Salt Restriction Lower Blood Pressure in Type 2 Diabetes?

Yes, according to an article in Nutrition, Metabolism & Cardiovascular Disease. The systolic pressure lowering is 5-6 points, but only 1-2 points on average for diastolic pressure. This degree of BP lowering is not dramatic, but might prevent an escalation of antihypertensive drug dosing or initiation of an additional drug.

Blood pressure control is also extremely important for protection of heart, kidneys, and brain.

Steve Parker, M.D.

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Should You Reduce Your Aspirin Dose from 325 to 81 mg/day?

Photo by Anna Shvets on Pexels.com

For patients with established cardiovascular disease, a recent study found that aspirin 81 mg/day was just as effective as 325 mg/day in preventing combined risk of death and hospitalization for heart attack or stroke. Rates of major bleeding were the same regardless of dose.

Click for details at NEJM.

Don’t make changes in your medication regimen without consulting your personal physician.

Steve Parker, M.D.

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High Blood Pressure: What’s the Number to Shoot For?

Not a bad monitor

First, recall that blood pressure is reported as two numbers: systolic and diastolic. E.g., 135/92. The first number is the systolic number. A systolic pressure goal of under 120 mmHg may be better than the traditional goal of under 140, at least if you’re “at increased risk for cardiovascular disease.” The study at hand excluded folks with diabetes or prior stroke.

We randomly assigned 9,361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

RESULTS

At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Steve Parker, M.D.

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Diabetes Drug Semaglutide Promotes Weight Loss

“Should I wait for FDA approval?”

I met a patient at the hospital recently who was taking semaglutide. I asked how long he had diabetes and he told me he didn’t have diabetes: his PCP (primary care physician) was prescribing it for weight loss.

A recent study enrolled 1,961 obese non-diabetics and found a very significant weight loss difference compared to the placebo group. I expect Novo Nordisc will be asking for FDA approval to market semaglutide, originally for diabetes, as a weight-loss drug. But what happens after you quit taking the drug? I bet you know.

In participants with overweight or obesity, 2.4 mg of semaglutide [injected] once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.

Source: Once-Weekly Semaglutide in Adults with Overweight or Obesity | NEJM

Steve Parker, M.D.

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Which Diets Help Lower Blood Pressure?

Probably all on the Portfolio Diet

Increasingly, I’m suspicious of results from meta-analyses. Anyway, here’s the abstract of one from American Journal of Clinical Nutrition in 2020. In case you’re not familiar with the LDL-lowering, vegetarian, “portfolio diet,” click for an infographic.

Background: Many systematic reviews and meta-analyses have assessed the efficacy of dietary patterns on blood pressure (BP) lowering but their findings are largely conflicting.

Objective: This umbrella review aims to provide an update on the available evidence for the efficacy of different dietary patterns on BP lowering.

Methods: PubMed and Scopus databases were searched to identify relevant studies through to June 2020. Systematic reviews with meta-analyses of randomized controlled trials (RCTs) were eligible if they measured the effect of dietary patterns on systolic (SBP) and/or diastolic blood pressure (DBP) levels. The methodological quality of included systematic reviews was assessed by A Measurement Tool to Assess Systematic Review version 2. The efficacy of each dietary pattern was summarized qualitatively. The confidence of the effect estimates for each dietary pattern was graded using the NutriGrade scoring system.

Results: Fifty systematic reviews and meta-analyses of RCTs were eligible for review. Twelve dietary patterns namely the Dietary Approaches to Stop Hypertension (DASH), Mediterranean, Nordic, vegetarian, low-salt, low-carbohydrate, low-fat, high-protein, low glycemic index, portfolio, pulse, and Paleolithic diets were included in this umbrella review. Among these dietary patterns, the DASH diet was associated with the greatest overall reduction in BP with unstandardized mean differences ranging from -3.20 to -7.62 mmHg for SBP and from -2.50 to -4.22 mmHg for DBP. Adherence to Nordic, portfolio, and low-salt diets also significantly decreased SBP and DBP levels. In contrast, evidence for the efficacy of BP lowering using the Mediterranean, vegetarian, Paleolithic, low-carbohydrate, low glycemic index, high-protein, and low-fat diets was inconsistent.

Conclusion: Adherence to the DASH, Nordic, and portfolio diets effectively reduced BP. Low-salt diets significantly decreased BP levels in normotensive Afro-Caribbean people and in hypertensive patients of all ethnic origins.

Source: Efficacy of different dietary patterns on lowering of blood pressure level: an umbrella review – PubMed

Steve Parker, M.D.

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High Glycemic Index Eating Linked to Higher Risk of Cardiovascular Disease and Death

Haven’t we known this for years? Click for definition and discussion of glycemic index and glycemic load.

“One little piece won’t hurt . . .”

From New England Journal of Medicine:

Most data regarding the association between the glycemic index and cardiovascular disease come from high-income Western populations, with little information from non-Western countries with low or middle incomes. To fill this gap, data are needed from a large, geographically diverse population.

METHODS

This analysis includes 137,851 participants between the ages of 35 and 70 years living on five continents, with a median follow-up of 9.5 years. We used country-specific food-frequency questionnaires to determine dietary intake and estimated the glycemic index and glycemic load on the basis of the consumption of seven categories of carbohydrate foods. We calculated hazard ratios using multivariable Cox frailty models. The primary outcome was a composite of a major cardiovascular event (cardiovascular death, nonfatal myocardial infarction, stroke, and heart failure) or death from any cause.

RESULTS

In the study population, 8780 deaths and 8252 major cardiovascular events occurred during the follow-up period. After performing extensive adjustments comparing the lowest and highest glycemic-index quintiles, we found that a diet with a high glycemic index was associated with an increased risk of a major cardiovascular event or death, both among participants with preexisting cardiovascular disease (hazard ratio, 1.51; 95% confidence interval [CI], 1.25 to 1.82) and among those without such disease (hazard ratio, 1.21; 95% CI, 1.11 to 1.34). Among the components of the primary outcome, a high glycemic index was also associated with an increased risk of death from cardiovascular causes. The results with respect to glycemic load were similar to the findings regarding the glycemic index among the participants with cardiovascular disease at baseline, but the association was not significant among those without preexisting cardiovascular disease.

CONCLUSIONS

In this study, a diet with a high glycemic index was associated with an increased risk of cardiovascular disease and death.

Source: Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality | NEJM

The low-carb Mediterranean diet is low glycemic index.

Steve Parker, M.D.

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